Publications by authors named "Shofiqul Islam"

62 Publications

Causal ordering among risk factors in the PURE study - Authors' reply.

Lancet 2021 01;397(10271):279

Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, ON L8L 2X2, Canada; Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada.

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http://dx.doi.org/10.1016/S0140-6736(21)00091-XDOI Listing
January 2021

Global variations in the prevalence, treatment, and impact of atrial fibrillation in a multi-national cohort of 153,152 middle-aged individuals.

Cardiovasc Res 2020 Aug 10. Epub 2020 Aug 10.

Population Health Research Institute, McMaster University, Canada.

Aims: To compare the prevalence of electrocardiogram (ECG)-documented atrial fibrillation (or flutter) (AF) across eight regions of the world, and to examine anti-thrombotic use and clinical outcomes.

Methods And Results: Baseline ECGs were collected in 153,152 middle-aged participants (ages 35 to 70 years) to document AF in two community-based studies, spanning 20 countries. Medication use and clinical outcome data (mean follow up of 7.4 years) were available in one cohort. Cross sectional analyses were performed to document the prevalence of AF and medication use, and associations between AF and clinical events were examined prospectively. Mean age of participants was 52.1 years, and 57.7% were female. Age and sex-standardized prevalence of AF varied 12-fold between regions; with the highest in North America, Europe, China and Southeast Asia (270-360 cases per 100,000 persons); and lowest in the Middle East, Africa, and South Asia (30-60 cases per 100,000 persons)(p < 0.001). Compared with low-income countries (LICs), AF prevalence was 7-fold higher in middle-income countries (MICs) and 11-fold higher in high-income countries (HICs)(p < 0.001). Differences in AF prevalence remained significant after adjusting for traditional AF risk factors. In LICs/MICs, 24% of participants with AF and a CHADS2 score ≥1 received anti-thrombotic therapy, compared with 85% in HICs. AF was associated with an increased risk of stroke (hazard ratio [HR: 2.29; 95% confidence interval [CI] 1.49-3.52) and death (HR: 2.97; 95% CI 2.25-3.93); with similar rates in different country income levels.

Conclusions: Large variations in AF prevalence occur in different regions and country income settings, but this is only partially explained by traditional AF risk factors. Anti-thrombotic therapy is infrequently used in poorer countries despite the high risk of stroke associated with AF.

Translational Perspective: We examined atrial fibrillation (AF) prevalence in 153,152 middle-aged participants spanning 20 countries. Age and sex-standardized prevalence of AF varied by as much as 12-fold between regions; highest in North America, Europe, China and Southeast Asia (270-360 cases per 100,000 persons); and lowest in the Middle East, Africa, and South Asia (30-60 cases per 100,000 persons)(p < 0.001); and by as much as 11-fold between groups of countries at different income levels (p < 0.001). Global variations were poorly explained by traditional AF risk factors. Future studies are needed to understand the predominant determinants driving the variation in AF burden across different regions of the world.
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http://dx.doi.org/10.1093/cvr/cvaa241DOI Listing
August 2020

Cardiovascular risk in hypertension: open questions about HOPE 4 - Authors' reply.

Lancet 2020 08;396(10247):310-311

Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, ON L8L 2X2, Canada; Department of Health Research Methods, Evidence and Impact, McMaster University Faculty of Health Sciences, Hamilton, ON, Canada.

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http://dx.doi.org/10.1016/S0140-6736(20)30616-4DOI Listing
August 2020

Arsenic fractionation in sediments and speciation in muscles of fish, Chrysichthys nigrodigitatus from a contaminated tropical Lagoon, Nigeria.

Chemosphere 2020 Oct 20;256:127134. Epub 2020 May 20.

Global Centre for Environmental Remediation (GCER), Faculty of Science, The University of Newcastle, Callaghan Campus, Callaghan, NSW, 2308, Australia; Cooperative Research Centre for Contamination Assessment and Remediation of the Environment (CRC CARE), ATC Building, Callaghan, NSW, 2308, Australia.

This study assesses arsenic (As) fractionation in sediments and speciation in muscle tissues of Bagrid catfish, Chrysichthys nigrodigitatus from Lagos Lagoon, southwest Nigeria to determine risks to ecological receptors and humans. Residual As was the predominant geochemical fraction (86.2%) in sediments. Arsenite [As (III)] concentrations which ranged from 0.06 to 0.53 mg kg in catfish muscle tissue, accounting for 25.9% of total As was the dominant species. Less toxic dimethylarsinic acid (DMA) which varied between 0.06 and 0.27 mg kg made up to 10.8% of total As in catfish muscle tissue. Estimated human average daily intake (ADI) of As as As (III) and DMA were 1.35 × 10 and 0.62 × 10 mg kg BW with corresponding hazard quotients (HQs) of 0.45 and 0.21, respectively, indicate no apparent health hazard to adult consumers. The incremental lifetime cancer risks (ILCR) of 0.78 × 10 for total As, 0.20 × 10 for As (III), and 0.93 × 10 for DMA, for adults from the consumption of catfish is slightly higher than the US EPA threshold and indicates moderate carcinogenic risk. Furthermore, 12.5% bioavailable fraction of As in sediment and relatively higher levels of As (III) in fish tissues has ecological and public health implications.
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http://dx.doi.org/10.1016/j.chemosphere.2020.127134DOI Listing
October 2020

Modifiable risk factors, cardiovascular disease, and mortality in 155 722 individuals from 21 high-income, middle-income, and low-income countries (PURE): a prospective cohort study.

Lancet 2020 03 3;395(10226):795-808. Epub 2019 Sep 3.

Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Quebec, QC, Canada.

Background: Global estimates of the effect of common modifiable risk factors on cardiovascular disease and mortality are largely based on data from separate studies, using different methodologies. The Prospective Urban Rural Epidemiology (PURE) study overcomes these limitations by using similar methods to prospectively measure the effect of modifiable risk factors on cardiovascular disease and mortality across 21 countries (spanning five continents) grouped by different economic levels.

Methods: In this multinational, prospective cohort study, we examined associations for 14 potentially modifiable risk factors with mortality and cardiovascular disease in 155 722 participants without a prior history of cardiovascular disease from 21 high-income, middle-income, or low-income countries (HICs, MICs, or LICs). The primary outcomes for this paper were composites of cardiovascular disease events (defined as cardiovascular death, myocardial infarction, stroke, and heart failure) and mortality. We describe the prevalence, hazard ratios (HRs), and population-attributable fractions (PAFs) for cardiovascular disease and mortality associated with a cluster of behavioural factors (ie, tobacco use, alcohol, diet, physical activity, and sodium intake), metabolic factors (ie, lipids, blood pressure, diabetes, obesity), socioeconomic and psychosocial factors (ie, education, symptoms of depression), grip strength, and household and ambient pollution. Associations between risk factors and the outcomes were established using multivariable Cox frailty models and using PAFs for the entire cohort, and also by countries grouped by income level. Associations are presented as HRs and PAFs with 95% CIs.

Findings: Between Jan 6, 2005, and Dec 4, 2016, 155 722 participants were enrolled and followed up for measurement of risk factors. 17 249 (11·1%) participants were from HICs, 102 680 (65·9%) were from MICs, and 35 793 (23·0%) from LICs. Approximately 70% of cardiovascular disease cases and deaths in the overall study population were attributed to modifiable risk factors. Metabolic factors were the predominant risk factors for cardiovascular disease (41·2% of the PAF), with hypertension being the largest (22·3% of the PAF). As a cluster, behavioural risk factors contributed most to deaths (26·3% of the PAF), although the single largest risk factor was a low education level (12·5% of the PAF). Ambient air pollution was associated with 13·9% of the PAF for cardiovascular disease, although different statistical methods were used for this analysis. In MICs and LICs, household air pollution, poor diet, low education, and low grip strength had stronger effects on cardiovascular disease or mortality than in HICs.

Interpretation: Most cardiovascular disease cases and deaths can be attributed to a small number of common, modifiable risk factors. While some factors have extensive global effects (eg, hypertension and education), others (eg, household air pollution and poor diet) vary by a country's economic level. Health policies should focus on risk factors that have the greatest effects on averting cardiovascular disease and death globally, with additional emphasis on risk factors of greatest importance in specific groups of countries.

Funding: Full funding sources are listed at the end of the paper (see Acknowledgments).
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http://dx.doi.org/10.1016/S0140-6736(19)32008-2DOI Listing
March 2020

A community-based comprehensive intervention to reduce cardiovascular risk in hypertension (HOPE 4): a cluster-randomised controlled trial.

Lancet 2019 10 2;394(10205):1231-1242. Epub 2019 Sep 2.

Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, ON, Canada; Department of Health Research Methods, Evidence and Impact, McMaster University Faculty of Health Sciences, Hamilton, ON, Canada.

Background: Hypertension is the leading cause of cardiovascular disease globally. Despite proven benefits, hypertension control is poor. We hypothesised that a comprehensive approach to lowering blood pressure and other risk factors, informed by detailed analysis of local barriers, would be superior to usual care in individuals with poorly controlled or newly diagnosed hypertension. We tested whether a model of care involving non-physician health workers (NPHWs), primary care physicians, family, and the provision of effective medications, could substantially reduce cardiovascular disease risk.

Methods: HOPE 4 was an open, community-based, cluster-randomised controlled trial involving 1371 individuals with new or poorly controlled hypertension from 30 communities (defined as townships) in Colombia and Malaysia. 16 communities were randomly assigned to control (usual care, n=727), and 14 (n=644) to the intervention. After community screening, the intervention included treatment of cardiovascular disease risk factors by NPHWs using tablet computer-based simplified management algorithms and counselling programmes; free antihypertensive and statin medications recommended by NPHWs but supervised by physicians; and support from a family member or friend (treatment supporter) to improve adherence to medications and healthy behaviours. The primary outcome was the change in Framingham Risk Score 10-year cardiovascular disease risk estimate at 12 months between intervention and control participants. The HOPE 4 trial is registered at ClinicalTrials.gov, NCT01826019.

Findings: All communities completed 12-month follow-up (data on 97% of living participants, n=1299). The reduction in Framingham Risk Score for 10-year cardiovascular disease risk was -6·40% (95% CI 8·00 to -4·80) in the control group and -11·17% (-12·88 to -9·47) in the intervention group, with a difference of change of -4·78% (95% CI -7·11 to -2·44, p<0·0001). There was an absolute 11·45 mm Hg (95% CI -14·94 to -7·97) greater reduction in systolic blood pressure, and a 0·41 mmol/L (95% CI -0·60 to -0·23) reduction in LDL with the intervention group (both p<0·0001). Change in blood pressure control status (<140 mm Hg) was 69% in the intervention group versus 30% in the control group (p<0·0001). There were no safety concerns with the intervention.

Interpretation: A comprehensive model of care led by NPHWs, involving primary care physicians and family that was informed by local context, substantially improved blood pressure control and cardiovascular disease risk. This strategy is effective, pragmatic, and has the potential to substantially reduce cardiovascular disease compared with current strategies that are typically physician based.

Funding: Canadian Institutes of Health Research; Grand Challenges Canada; Ontario SPOR Support Unit and the Ontario Ministry of Health and Long-Term Care; Boehringer Ingelheim; Department of Management of Non-Communicable Diseases, WHO; and Population Health Research Institute. VIDEO ABSTRACT.
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http://dx.doi.org/10.1016/S0140-6736(19)31949-XDOI Listing
October 2019

Mortality and cardiovascular and respiratory morbidity in individuals with impaired FEV (PURE): an international, community-based cohort study.

Lancet Glob Health 2019 05;7(5):e613-e623

Population Health Research Institute, Department of Medicine, McMaster University and Hamilton Health Sciences, Hamilton, ON, Canada.

Background: The associations between the extent of forced expiratory volume in 1 s (FEV) impairment and mortality, incident cardiovascular disease, and respiratory hospitalisations are unclear, and how these associations might vary across populations is unknown.

Methods: In this international, community-based cohort study, we prospectively enrolled adults aged 35-70 years who had no intention of moving residences for 4 years from rural and urban communities across 17 countries. A portable spirometer was used to assess FEV. FEV values were standardised within countries for height, age, and sex, and expressed as a percentage of the country-specific predicted FEV value (FEV%). FEV% was categorised as no impairment (FEV% ≥0 SD from country-specific mean), mild impairment (FEV% <0 SD to -1 SD), moderate impairment (FEV% <-1 SD to -2 SDs), and severe impairment (FEV% <-2 SDs [ie, clinically abnormal range]). Follow-up was done every 3 years to collect information on mortality, cardiovascular disease outcomes (including myocardial infarction, stroke, sudden death, or congestive heart failure), and respiratory hospitalisations (from chronic obstructive pulmonary disease, asthma, pneumonia, tuberculosis, or other pulmonary conditions). Fully adjusted hazard ratios (HRs) were calculated by multilevel Cox regression.

Findings: Among 126 359 adults with acceptable spirometry data available, during a median 7·8 years (IQR 5·6-9·5) of follow-up, 5488 (4·3%) deaths, 5734 (4·5%) cardiovascular disease events, and 1948 (1·5%) respiratory hospitalisation events occurred. Relative to the no impairment group, mild to severe FEV% impairments were associated with graded increases in mortality (HR 1·27 [95% CI 1·18-1·36] for mild, 1·74 [1·60-1·90] for moderate, and 2·54 [2·26-2·86] for severe impairment), cardiovascular disease (1·18 [1·10-1·26], 1·39 [1·28-1·51], 2·02 [1·75-2·32]), and respiratory hospitalisation (1·39 [1·24-1·56], 2·02 [1·75-2·32], 2·97 [2·45-3·60]), and this pattern persisted in subgroup analyses considering country income level and various baseline risk factors. Population-attributable risk for mortality (adjusted for age, sex, and country income) from mildly to moderately reduced FEV% (24·7% [22·2-27·2]) was larger than that from severely reduced FEV% (3·7% [2·1-5·2]) and from tobacco use (19·7% [17·2-22·3]), previous cardiovascular disease (5·5% [4·5-6·5]), and hypertension (17·1% [14·6-19·6]). Population-attributable risk for cardiovascular disease from mildly to moderately reduced FEV was 17·3% (14·8-19·7), second only to the contribution of hypertension (30·1% [27·6-32·5]).

Interpretation: FEV is an independent and generalisable predictor of mortality, cardiovascular disease, and respiratory hospitalisation, even across the clinically normal range (mild to moderate impairment).

Funding: Population Health Research Institute, the Canadian Institutes of Health Research, Heart and Stroke Foundation of Ontario, Ontario Ministry of Health and Long-Term Care, AstraZeneca, Sanofi-Aventis, Boehringer Ingelheim, Servier, and GlaxoSmithKline, Novartis, and King Pharma. Additional funders are listed in the appendix.
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http://dx.doi.org/10.1016/S2214-109X(19)30070-1DOI Listing
May 2019

Impact of water and fertilizer management on arsenic bioaccumulation and speciation in rice plants grown under greenhouse conditions.

Chemosphere 2019 Jan 28;214:606-613. Epub 2018 Sep 28.

Global Centre for Environmental Remediation (GCER), Faculty of Science, The University of Newcastle, Callaghan, NSW, 2308, Australia; Cooperative Research Centre for Contamination Assessment and Remediation of the Environment (CRC CARE), The University of Newcastle, Callaghan, NSW, 2308, Australia. Electronic address:

Arsenic (As), a non-threshold class I carcinogen, is a main source of human exposure to inorganic As for billions of people worldwide. Rice is much more effectual in accruing As into its grain and other parts. Therefore, strategies to reduce As accumulation in rice should be adopted. The impact of water [Alternate Wetting and Drying (AWD), incessant flooding (CF)] and fertilizer management [Silicon (Si@ control, 10 and 20 mg/kg soil) and Phosphorus (P@ control, 12.5 and 25.0 mg/kg soil)] on the bioaccumulation of As in rice plants under different As-graded paddy soils (control, 10, 20 mg/kg) using an Australian rice variety (cv. Sherpa) was investigated under greenhouse conditions. Results indicated that, arsenite accounted for >80% of the total inorganic As in pore water and total As concentration declined from 933 μg/L to 177 μg/L with time. AWD irrigation practice with Si fertilization significantly reduced the total As levels in pore water. Arsenic concentration in different rice plant tissues showed significant variations due to water and fertilizer management. Lower concentrations of As in rice grains were observed using AWD (average 93.0 μg/kg) than those observed in CF (average 121 μg/kg) irrigation practice. The addition of Si also significantly (p < 0.03) decreased As uptake by rice plants while adding of P has no significant effect and this is also true for Si and P interaction. AWD irrigation practice with Si fertilization resulted in a reduction of grain As level at around 12%-21%, while grain yield increased by 13%.
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http://dx.doi.org/10.1016/j.chemosphere.2018.09.158DOI Listing
January 2019

Rationale and design of a cluster randomized trial of a multifaceted intervention in people with hypertension: The Heart Outcomes Prevention and Evaluation 4 (HOPE-4) Study.

Am Heart J 2018 09 22;203:57-66. Epub 2018 Jun 22.

Population Health Research Institute, Hamilton, Ontario, Canada; Department of Medicine, Division of Cardiology, McMaster University, Hamilton, Ontario, Canada.

Background: Cardiovascular disease is the leading cause of death throughout the world, with the majority of deaths occurring in low- and middle-income countries. Despite clear evidence for the benefits of blood pressure reduction and availability of safe and low-cost medications, most individuals are either unaware of their condition or not adequately treated.

Objective: The primary objective of this study is to evaluate whether a community-based, multifaceted intervention package primarily provided by nonphysician health workers can improve long-term cardiovascular risk in people with hypertension by addressing identified barriers at the patient, health care provider, and health system levels.

Methods/design: HOPE-4 is a community-based, parallel-group, cluster randomized controlled trial involving 30 communities (1,376 participants) in Colombia and Malaysia. Participants ≥50 years old and with newly diagnosed or poorly controlled hypertension were included. Communities were randomized to usual care or to a multifaceted intervention package that entails (1) detection, treatment, and control of cardiovascular risk factors by nonphysician health workers in the community, who use tablet-based simplified management algorithms, decision support, and counseling programs; (2) free dispensation of combination antihypertensive and cholesterol-lowering medications, supervised by local physicians; and (3) support from a participant-nominated treatment supporter (either a friend or family member). The primary outcome is the change in Framingham Risk Score after 12 months between the intervention and control communities. Secondary outcomes including change in blood pressure, lipid levels, and Interheart Risk Score will be evaluated.

Significance: If successful, the study could serve as a model to develop low-cost, effective, and scalable strategies to reduce cardiovascular risk in people with hypertension.
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http://dx.doi.org/10.1016/j.ahj.2018.06.004DOI Listing
September 2018

Rationale and design of a cluster randomized trial of a multifaceted intervention in people with hypertension: The Heart Outcomes Prevention and Evaluation 4 (HOPE-4) Study.

Am Heart J 2018 09 22;203:57-66. Epub 2018 Jun 22.

Population Health Research Institute, Hamilton, Ontario, Canada; Department of Medicine, Division of Cardiology, McMaster University, Hamilton, Ontario, Canada.

Background: Cardiovascular disease is the leading cause of death throughout the world, with the majority of deaths occurring in low- and middle-income countries. Despite clear evidence for the benefits of blood pressure reduction and availability of safe and low-cost medications, most individuals are either unaware of their condition or not adequately treated.

Objective: The primary objective of this study is to evaluate whether a community-based, multifaceted intervention package primarily provided by nonphysician health workers can improve long-term cardiovascular risk in people with hypertension by addressing identified barriers at the patient, health care provider, and health system levels.

Methods/design: HOPE-4 is a community-based, parallel-group, cluster randomized controlled trial involving 30 communities (1,376 participants) in Colombia and Malaysia. Participants ≥50 years old and with newly diagnosed or poorly controlled hypertension were included. Communities were randomized to usual care or to a multifaceted intervention package that entails (1) detection, treatment, and control of cardiovascular risk factors by nonphysician health workers in the community, who use tablet-based simplified management algorithms, decision support, and counseling programs; (2) free dispensation of combination antihypertensive and cholesterol-lowering medications, supervised by local physicians; and (3) support from a participant-nominated treatment supporter (either a friend or family member). The primary outcome is the change in Framingham Risk Score after 12 months between the intervention and control communities. Secondary outcomes including change in blood pressure, lipid levels, and Interheart Risk Score will be evaluated.

Significance: If successful, the study could serve as a model to develop low-cost, effective, and scalable strategies to reduce cardiovascular risk in people with hypertension.
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http://dx.doi.org/10.1016/j.ahj.2018.06.004DOI Listing
September 2018

Rationale and design of a cluster randomized trial of a multifaceted intervention in people with hypertension: The Heart Outcomes Prevention and Evaluation 4 (HOPE-4) Study.

Am Heart J 2018 09 22;203:57-66. Epub 2018 Jun 22.

Population Health Research Institute, Hamilton, Ontario, Canada; Department of Medicine, Division of Cardiology, McMaster University, Hamilton, Ontario, Canada.

Background: Cardiovascular disease is the leading cause of death throughout the world, with the majority of deaths occurring in low- and middle-income countries. Despite clear evidence for the benefits of blood pressure reduction and availability of safe and low-cost medications, most individuals are either unaware of their condition or not adequately treated.

Objective: The primary objective of this study is to evaluate whether a community-based, multifaceted intervention package primarily provided by nonphysician health workers can improve long-term cardiovascular risk in people with hypertension by addressing identified barriers at the patient, health care provider, and health system levels.

Methods/design: HOPE-4 is a community-based, parallel-group, cluster randomized controlled trial involving 30 communities (1,376 participants) in Colombia and Malaysia. Participants ≥50 years old and with newly diagnosed or poorly controlled hypertension were included. Communities were randomized to usual care or to a multifaceted intervention package that entails (1) detection, treatment, and control of cardiovascular risk factors by nonphysician health workers in the community, who use tablet-based simplified management algorithms, decision support, and counseling programs; (2) free dispensation of combination antihypertensive and cholesterol-lowering medications, supervised by local physicians; and (3) support from a participant-nominated treatment supporter (either a friend or family member). The primary outcome is the change in Framingham Risk Score after 12 months between the intervention and control communities. Secondary outcomes including change in blood pressure, lipid levels, and Interheart Risk Score will be evaluated.

Significance: If successful, the study could serve as a model to develop low-cost, effective, and scalable strategies to reduce cardiovascular risk in people with hypertension.
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http://dx.doi.org/10.1016/j.ahj.2018.06.004DOI Listing
September 2018

Associations of fats and carbohydrate intake with cardiovascular disease and mortality in 18 countries from five continents (PURE): a prospective cohort study.

Lancet 2017 Nov 29;390(10107):2050-2062. Epub 2017 Aug 29.

Population Health Research Institute, McMaster University, Hamilton, ON, Canada.

Background: The relationship between macronutrients and cardiovascular disease and mortality is controversial. Most available data are from European and North American populations where nutrition excess is more likely, so their applicability to other populations is unclear.

Methods: The Prospective Urban Rural Epidemiology (PURE) study is a large, epidemiological cohort study of individuals aged 35-70 years (enrolled between Jan 1, 2003, and March 31, 2013) in 18 countries with a median follow-up of 7·4 years (IQR 5·3-9·3). Dietary intake of 135 335 individuals was recorded using validated food frequency questionnaires. The primary outcomes were total mortality and major cardiovascular events (fatal cardiovascular disease, non-fatal myocardial infarction, stroke, and heart failure). Secondary outcomes were all myocardial infarctions, stroke, cardiovascular disease mortality, and non-cardiovascular disease mortality. Participants were categorised into quintiles of nutrient intake (carbohydrate, fats, and protein) based on percentage of energy provided by nutrients. We assessed the associations between consumption of carbohydrate, total fat, and each type of fat with cardiovascular disease and total mortality. We calculated hazard ratios (HRs) using a multivariable Cox frailty model with random intercepts to account for centre clustering.

Findings: During follow-up, we documented 5796 deaths and 4784 major cardiovascular disease events. Higher carbohydrate intake was associated with an increased risk of total mortality (highest [quintile 5] vs lowest quintile [quintile 1] category, HR 1·28 [95% CI 1·12-1·46], p=0·0001) but not with the risk of cardiovascular disease or cardiovascular disease mortality. Intake of total fat and each type of fat was associated with lower risk of total mortality (quintile 5 vs quintile 1, total fat: HR 0·77 [95% CI 0·67-0·87], p<0·0001; saturated fat, HR 0·86 [0·76-0·99], p=0·0088; monounsaturated fat: HR 0·81 [0·71-0·92], p<0·0001; and polyunsaturated fat: HR 0·80 [0·71-0·89], p<0·0001). Higher saturated fat intake was associated with lower risk of stroke (quintile 5 vs quintile 1, HR 0·79 [95% CI 0·64-0·98], p=0·0498). Total fat and saturated and unsaturated fats were not significantly associated with risk of myocardial infarction or cardiovascular disease mortality.

Interpretation: High carbohydrate intake was associated with higher risk of total mortality, whereas total fat and individual types of fat were related to lower total mortality. Total fat and types of fat were not associated with cardiovascular disease, myocardial infarction, or cardiovascular disease mortality, whereas saturated fat had an inverse association with stroke. Global dietary guidelines should be reconsidered in light of these findings.

Funding: Full funding sources listed at the end of the paper (see Acknowledgments).
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http://dx.doi.org/10.1016/S0140-6736(17)32252-3DOI Listing
November 2017

Effect of irrigation and genotypes towards reduction in arsenic load in rice.

Sci Total Environ 2017 Dec 25;609:311-318. Epub 2017 Jul 25.

Global Centre for Environmental Remediation (GCER), Faculty of Science, The University of Newcastle, Callaghan, NSW 2308, Australia; Cooperative Research Centre for Contamination Assessment and Remediation of the Environment (CRC CARE), The University of Newcastle, Callaghan, NSW 2308, Australia. Electronic address:

Arsenic (As) bioaccumulation in rice grains has been identified as a major problem in Bangladesh and many other parts of the world. Suitable rice genotypes along with proper water management practice regulating As levels in rice plants must be chosen and implemented. A field study was conducted to investigate the effect of continuous flooding (CF) and alternate wetting and drying (AWD) irrigation on the bioaccumulation of As in ten rice cultivars at three locations having different levels of soil As and irrigation water As. Results showed that As concentration in different parts of rice plants varied significantly (P<0.0001) with rice genotypes and irrigation practices in the three study locations. Lower levels of As in rice were found in AWD irrigation practice compared to CF irrigation practice. Higher grain As bioaccumulation was detected in plants in areas of high soil As in combination with CF irrigation practice. Our data show that use of AWD irrigation practice with suitable genotypes led to 17 to 35% reduction in grain As level, as well as 7 to 38% increase in grain yield. Overall, this study advances our understanding that, for moderate to high levels of As contamination, the Binadhan-5, Binadhan-6, Binadhan-8, Binadhan-10 and BRRI dhan47 varieties were quite promising to mitigate As induced human health risk.
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http://dx.doi.org/10.1016/j.scitotenv.2017.07.111DOI Listing
December 2017

Comparing the performance of linear and nonlinear principal components in the context of high-dimensional genomic data integration.

Stat Appl Genet Mol Biol 2017 07;16(3):199-216

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Linear principal component analysis (PCA) is a widely used approach to reduce the dimension of gene or miRNA expression data sets. This method relies on the linearity assumption, which often fails to capture the patterns and relationships inherent in the data. Thus, a nonlinear approach such as kernel PCA might be optimal. We develop a copula-based simulation algorithm that takes into account the degree of dependence and nonlinearity observed in these data sets. Using this algorithm, we conduct an extensive simulation to compare the performance of linear and kernel principal component analysis methods towards data integration and death classification. We also compare these methods using a real data set with gene and miRNA expression of lung cancer patients. First few kernel principal components show poor performance compared to the linear principal components in this occasion. Reducing dimensions using linear PCA and a logistic regression model for classification seems to be adequate for this purpose. Integrating information from multiple data sets using either of these two approaches leads to an improved classification accuracy for the outcome.
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http://dx.doi.org/10.1515/sagmb-2016-0066DOI Listing
July 2017

Investigating the relationship between lead speciation and bioaccessibility of mining impacted soils and dusts.

Environ Sci Pollut Res Int 2017 Jul 4;24(20):17056-17067. Epub 2017 Jun 4.

Global Center for Environmental Remediation, University of Newcastle, Callaghan Campus, Newcastle, NSW, 2308, Australia.

Lead (Pb) bioaccessibility measurements have been the subject of much research in recent years, given the desire to develop a cost-effective and reliable alternative method to estimate its bioavailability from soils and dusts. This study investigates the relationship between Pb bioaccessibility estimated using the Relative Bioavailability Leaching Procedure (RBALP) and solid phase speciation of Pb using mining impacted soils and associated dusts. Solid phase speciation was conducted prior to and after RBALP extractions. The average Pb concentrations were 59, 67, and 385 mg/kg for top soil, sub-soil, and house dust samples, respectively. Lead bioaccessibility in selected top soils and dusts ranged from 16.7 to 57.3% and 8.9 to 98.1%, respectively. Solid phase speciation of Pb in <250 μm residues prior to and after RBALP extraction revealed 83% decrease in Pb bound to carbonate fraction after RBALP extraction. This accounts for 69% of RBALP-extractable Pb. Besides contribution from carbonate bound Pb, 76.6 and 53.2% of Pb bound to Mn oxyhydroxides and amorphous Fe and Al oxyhydroxides contributed to bioaccessible Pb, respectively. However, Pb bound to Mn oxyhydroxides and amorphous Fe and Al oxyhydroxides account for only 13.8 and 20.0% of total RBALP-extractable Pb, respectively. Both non-specifically bound and easily exchangeable fractions and strongly bound inner-sphere complexes were also part of bioaccessible Pb. The present study demonstrates that bioaccessible Pb is released from both soil solution phase Pb as well as that from all soil solid phase with the most contribution being from Pb bound to carbonate mineral phase.
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http://dx.doi.org/10.1007/s11356-017-9250-8DOI Listing
July 2017

Geographical variation and age-related dietary exposure to arsenic in rice from Bangladesh.

Sci Total Environ 2017 Dec 25;601-602:122-131. Epub 2017 May 25.

Global Centre for Environmental Remediation (GCER), Faculty of Science and Information Technology, The University of Newcastle, Callaghan, NSW 2308, Australia; Cooperative Research Centre for Contamination Assessment and Remediation of the Environment (CRC CARE), The University of Newcastle, Callaghan, NSW 2308, Australia. Electronic address:

An extensive number (965) of rice samples collected by household survey from 73 upazilas (i.e. sub-districts) in Bangladesh was analyzed to determine regional variation, distribution and associated health risks from arsenic (As). No previous study had conducted a study examining such a large number of rice samples. The mean and median concentrations of total As were 126μg/kg and 107μg/kg, respectively, ranging from between 3 and 680μg/kg. Importantly, total As levels of aromatic rice were significantly lower (average 58μg/kg) than non-aromatic rice (average 150μg/kg) and also varied with rice grain size. The variation in As content was dominated by the location (47% among the upazilas, 71% among districts) and rice variety (14%). Inorganic As content in rice grain ranged between 11 and 502μg/kg (n=162) with the highest fraction being 98.6%. The daily intake of inorganic As from rice ranged between 0.38 and 1.92μg/kg BW in different districts. The incremental lifetime cancer risk (ILCR) for individuals due to the consumption of rice varied between 0.57×10 to 2.88×10 in different districts, and 0.54×10 to 2.12×10 in different varieties, higher than the US EPA threshold. The 2-10 age group experiences higher carcinogenic risks than others and females are more susceptible than males.
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http://dx.doi.org/10.1016/j.scitotenv.2017.05.184DOI Listing
December 2017

Prevalence, awareness, treatment and control of hypertension in four Middle East countries.

J Hypertens 2017 07;35(7):1457-1464

aHatta Hospital, Dubai Health Authority, Dubai, UAE bDepartment of Public Health Sciences, Loyola Medical Center, Maywood, Illinois, USA cPopulation Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, Canada dDepartment of Cardiac Sciences, King Fahad Cardiac Center, College of Medicine, King Saud University, Riyadh, Saudi Arabia eHypertension Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran fPrimary Healthcare, Dubai Health Authority, Dubai, UAE gUnited Nations Relief and Works Agency for Palestine Refugees in the Near East, Jerusalem, Palestine.

Objective: We report the prevalence, awareness, treatment, and control of hypertension across four Middle Eastern countries (Iran, Occupied Palestinian Territory, Saudi Arabia, and United Arab Emirates), using a standardized and uniform method.

Methods: The Prospective Urban Rural Epidemiology study enrolled participants from 52 urban and 35 rural communities from four countries in the Middle East. We report results using definitions of hypertension, prevalence, awareness, treatment, and control, and the standards for uniform reporting of hypertension in adults as recently recommended by the World Hypertension League expert committee.

Results: Data for analyses were available on 10 516 participants, of whom 5082 (48%) were men. The mean age was 49 (±9.4) years for men and 48 (±9.3) years among women. A total of 3270 participants had hypertension (age-standardized rates, 33%), and n = 1807 (49%) of these participants were aware of their diagnosis. Of those with hypertension, n = 1754, (47%) were treated and only n = 673, (19%) had controlled blood pressure levels. Only 17% (n = 541) of those treated for hypertension received two or more blood pressure-lowering medications and 15% (n = 499) received statins. The prevalence, awareness, treatment, and control of blood pressure were higher among women and older (50-69 years) participants compared with men and younger individuals (30-49 years) (P < 0.0001 for all). The prevalence was higher in rural communities; however, awareness, treatment, and control were significantly higher among urban dwellers.

Conclusion: Findings from this study indicate the need for improvements in hypertension diagnosis and treatment in the Middle East, especially in rural communities, men and younger individuals.
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http://dx.doi.org/10.1097/HJH.0000000000001326DOI Listing
July 2017

Variation in arsenic bioavailability in rice genotypes using swine model: An animal study.

Sci Total Environ 2017 Dec 4;599-600:324-331. Epub 2017 May 4.

Global Centre for Environmental Remediation (GCER), The University of Newcastle, University Drive, Callaghan, NSW 2308, Australia; Cooperative Research Centre for Contamination Assessment and Remediation of the Environment (CRC CARE), The University of Newcastle, University Drive, Callaghan, NSW 2308, Australia. Electronic address:

An in vivo assay using swine was used to measure the absolute bioavailability (AB) of As from cooked rice of twelve genotypes commonly grown in Bangladesh. An assessment of both total As in rice and its bioavailability is crucial for estimating human exposure following dietary intake by the local community. Average As concentrations in each rice genotype ranged from 108±4μg/kg to 580±6μg/kg. Arsenic speciation shows that most of the rice genotype contains 73 to 100% inorganic As. Swine were administered with As orally and via intravenous method, i.e. injection and fed certain common Bangladeshi rice genotypes (cooked). Swine blood As levels were measured to calculate As bioavailability from rice. Pilot studies shows that for As(III) and As(V), 90.8±12.4% and 85.0±19.2% of the administered oral dose was absorbed from the gastrointestinal tract whereas organic As was poorly absorbed resulting in low bioavailability values 20.2±2.6% (MMA) to 31.2±3.4% (DMA), respectively. These studies demonstrates that rice genotypic characters influenced As bioavailability in rice grown in As-contaminated areas and the bioavailability varied between 25% and 94%. Arsenic in salt tolerant rice genotypes Binadhan-10 and BRRI dhan47 as well as brown rice genotypes Kheali Boro and Local Boro has lower bioavailability (<50%) compared to other rice genotypes. The most commonly cultivated and consumed variety (BRRI dhan28) has As bioavailability of 70%, which poses a significant risk to consumers. Calculation of maximum tolerable daily intake (MTDI) for humans due to consumption of rice based on bioavailability data was higher than those calculated based on inorganic and organic As concentration in rice genotypes.
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http://dx.doi.org/10.1016/j.scitotenv.2017.04.215DOI Listing
December 2017

Global mortality variations in patients with heart failure: results from the International Congestive Heart Failure (INTER-CHF) prospective cohort study.

Lancet Glob Health 2017 07 3;5(7):e665-e672. Epub 2017 May 3.

Population Health Research Institute, McMaster University, Hamilton, Canada.

Background: Most data on mortality and prognostic factors in patients with heart failure come from North America and Europe, with little information from other regions. Here, in the International Congestive Heart Failure (INTER-CHF) study, we aimed to measure mortality at 1 year in patients with heart failure in Africa, China, India, the Middle East, southeast Asia and South America; we also explored demographic, clinical, and socioeconomic variables associated with mortality.

Methods: We enrolled consecutive patients with heart failure (3695 [66%] clinic outpatients, 2105 [34%] hospital in patients) from 108 centres in six geographical regions. We recorded baseline demographic and clinical characteristics and followed up patients at 6 months and 1 year from enrolment to record symptoms, medications, and outcomes. Time to death was studied with Cox proportional hazards models adjusted for demographic and clinical variables, medications, socioeconomic variables, and region. We used the explained risk statistic to calculate the relative contribution of each level of adjustment to the risk of death.

Findings: We enrolled 5823 patients within 1 year (with 98% follow-up). Overall mortality was 16·5%: highest in Africa (34%) and India (23%), intermediate in southeast Asia (15%), and lowest in China (7%), South America (9%), and the Middle East (9%). Regional differences persisted after multivariable adjustment. Independent predictors of mortality included cardiac variables (New York Heart Association Functional Class III or IV, previous admission for heart failure, and valve disease) and non-cardiac variables (body-mass index, chronic kidney disease, and chronic obstructive pulmonary disease). 46% of mortality risk was explained by multivariable modelling with these variables; however, the remainder was unexplained.

Interpretation: Marked regional differences in mortality in patients with heart failure persisted after multivariable adjustment for cardiac and non-cardiac factors. Therefore, variations in mortality between regions could be the result of health-care infrastructure, quality and access, or environmental and genetic factors. Further studies in large, global cohorts are needed.

Funding: The study was supported by Novartis.
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http://dx.doi.org/10.1016/S2214-109X(17)30196-1DOI Listing
July 2017

Association of Household Wealth Index, Educational Status, and Social Capital with Hypertension Awareness, Treatment, and Control in South Asia.

Am J Hypertens 2017 Apr;30(4):373-381

Population Health Research Institute, Hamilton Health Sciences, McMaster University, Hamilton, Canada.

Objective: Hypertension control rates are low in South Asia. To determine association of measures of socioeconomic status (wealth, education, and social capital) with hypertension awareness, treatment, and control among urban and rural subjects in these countries we performed the present study.

Methods: We enrolled 33,423 subjects aged 35-70 years (women 56%, rural 53%, low-education status 51%, low household wealth 25%, low-social capital 33%) in 150 communities in India, Pakistan, and Bangladesh during 2003-2009. Prevalence of hypertension and its awareness, treatment, and control status and their association with wealth, education, and social capital were determined.

Results: Age-, sex-, and location-adjusted prevalence of hypertension in men was 31.5% (23.9-40.2%) and women was 32.6% (24.9-41.5%) with variations in prevalence across study sites (urban 30-56%, rural 11-43%). Prevalence was significantly greater in urban locations, older subjects, and participants with more wealth, greater education, and lower social capital index. Hypertension awareness was in 40.4% (urban 45.9, rural 32.5), treatment in 31.9% (urban 37.6, rural 23.6), and control in 12.9% (urban 15.4, rural 9.3). Control was lower in men and younger subjects. Hypertension awareness, treatment, and control were significantly lower, respectively, in lowest vs. highest wealth index tertile (26.2 vs. 50.6%, 16.9 vs. 44.0%, and 6.9 vs. 17.3%, P < 0.001) and lowest vs. highest educational status tertile (31.2 vs. 48.4%, 21.8 vs. 42.1%, and 7.8 vs. 19.2%, P < 0.001) while insignificant differences were observed in lowest vs. highest social capital index (38.2 vs. 36.1%, 35.1 vs. 27.8%, and 12.5 vs. 9.1%).

Conclusions: This study shows low hypertension awareness, treatment, and control in South Asia. Lower wealth and educational status are important in low hypertension awareness, treatment, and control.
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http://dx.doi.org/10.1093/ajh/hpw169DOI Listing
April 2017

Secondary CV Prevention in South America in a Community Setting: The PURE Study.

Glob Heart 2017 12 20;12(4):305-313. Epub 2016 Oct 20.

Population Health Research Institute, McMaster University, Hamilton, Ontario, Canada.

Background: Despite the availability of evidence-based therapies, there is no information on the use of medications for the secondary prevention of cardiovascular disease in urban and rural community settings in South America.

Objectives: This study sought to assess the use, and its predictors, of effective secondary prevention therapies in individuals with a history of coronary heart disease (CHD) or stroke.

Methods: In the PURE (Prospective Urban Rural Epidemiological) study, we enrolled 24,713 individuals from South America ages 35 to 70 years from 97 rural and urban communities in Argentina, Brazil, Chile, and Colombia. We assessed the use of proven therapies with standardized questionnaires. We report estimates of drug use at national, community, and individual levels and the independent predictors of their utilization through a multivariable analysis model.

Results: Of 24,713 individuals, 910 had a self-reported CHD event (at a median of 5 years earlier) and 407 had stroke (6 years earlier). The proportions of individuals with CHD who received antiplatelet medications (30.1%), beta-blockers (34.2%), angiotensin-converting enzyme inhibitors, or angiotensin-receptor blockers (36.0%), or statins (18.0%) were low; with even lower proportions among stroke patients (antiplatelets 24.3%, angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers 37.6%, statins 9.8%). A substantial proportion of patients did not receive any proven therapy (CHD 31%, stroke 54%). A minority of patients received either all 4 (4.1%) or 3 proven therapies (3.3%). Male sex, age >60 years, better education, more wealth, urban location, diabetes, and obesity were associated with higher rates of medication use. In a multivariable model, markers of wealth had the largest impact in secondary prevention.

Conclusions: There are large gaps in the use of proven medications for secondary prevention of cardiovascular disease in South America. Strategies to improve the sustained use of these medications will likely reduce cardiovascular disease burden substantially.
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http://dx.doi.org/10.1016/j.gheart.2016.06.001DOI Listing
December 2017

Arsenic accumulation in rice: Consequences of rice genotypes and management practices to reduce human health risk.

Environ Int 2016 Nov 17;96:139-155. Epub 2016 Sep 17.

Global Centre for Environmental Remediation (GCER), Faculty of Science and Information Technology, The University of Newcastle, Callaghan, NSW 2308, Australia; Cooperative Research Centre for Contamination Assessment and Remediation of the Environment (CRC CARE), The University of Newcastle, Callaghan, NSW 2308, Australia. Electronic address:

Rice is an essential staple food and feeds over half of the world's population. Consumption of rice has increased from limited intake in Western countries some 50years ago to major dietary intake now. Rice consumption represents a major route for inorganic arsenic (As) exposure in many countries, especially for people with a large proportion of rice in their daily diet as much as 60%. Rice plants are more efficient in assimilating As into its grains than other cereal crops and the accumulation may also adversely affect the quality of rice and their nutrition. Rice is generally grown as a lowland crop in flooded soils under reducing conditions. Under these conditions the bioavailability of As is greatly enhanced leading to excessive As bioaccumulation compared to that under oxidizing upland conditions. Inorganic As species are carcinogenic to humans and even at low levels in the diet pose a considerable risk to humans. There is a substantial genetic variation among the rice genotypes in grain-As accumulation as well as speciation. Identifying the extent of genetic variation in grain-As concentration and speciation of As compounds are crucial to determining the rice varieties which accumulate low inorganic As. Varietal selection, irrigation water management, use of fertilizer and soil amendments, cooking practices etc. play a vital role in reducing As exposure from rice grains. In the meantime assessing the bioavailability of As from rice is crucial to understanding human health exposure and reducing the risk.
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http://dx.doi.org/10.1016/j.envint.2016.09.006DOI Listing
November 2016

Age and Cardiovascular Risk Attributable to Apolipoprotein B, Low-Density Lipoprotein Cholesterol or Non-High-Density Lipoprotein Cholesterol.

J Am Heart Assoc 2016 10 13;5(10). Epub 2016 Oct 13.

Population Research Institute and McMaster University, Hamilton, Canada.

Background: Higher concentrations of the apolipoprotein B (apoB) lipoproteins increase the risk of cardiovascular disease. However, whether the risk associated with apoB lipoproteins varies with age has not been well examined.

Methods And Results: We determined the associations for total cholesterol, low-density lipoprotein (LDL)-cholesterol (LDL-C), non-high-density lipoprotein-cholesterol (non-HDL-C), apoB, apolipoprotein A-I (apoA-I), and HDL-cholesterol (HDL-C) with myocardial infarction at different ages in 11 760 controls and 8998 myocardial infarction cases of the INTERHEART Study. Logistic regression was used to compute the odds ratio of myocardial infarction for 1 SD change in each lipid marker by decade from <40 to >70 years of age. Except for those >70, plasma levels of total cholesterol, LDL-C, and non-HDL-C and apoB were greater in cases than controls. However, the average levels of these markers decreased significantly as age increased. By contrast, levels of apoA-I and HDL-C were significantly greater in controls than cases but increased significantly as age increased. The cardiovascular risk associated with the atherogenic lipid markers differed at different ages. Most notably, there was a significant decline in the odds ratio for total cholesterol, LDL-C, and non-HDL-C, and apoB with increases in age whereas the odds ratios associated with apoA-I and HDL-C were consistent across the age groups.

Conclusions: These data indicate that the risk of cardiovascular events associated with apoB particles is greater in younger compared to older individuals. This finding is consistent with greater relative benefit from LDL-lowering therapy in younger compared to older individuals and so argues for therapy in younger individuals with elevated lipids.
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http://dx.doi.org/10.1161/JAHA.116.003665DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5121475PMC
October 2016

Clinical Outcomes in 3343 Children and Adults With Rheumatic Heart Disease From 14 Low- and Middle-Income Countries: Two-Year Follow-Up of the Global Rheumatic Heart Disease Registry (the REMEDY Study).

Circulation 2016 Nov 4;134(19):1456-1466. Epub 2016 Oct 4.

From Cardiac Clinic, Department of Medicine, Groote Schuur Hospital and University of Cape Town, South Africa (L.Z., M.E.E., B.C., R.D., V.F., B.M.M.); Division of Paediatric Cardiology, Department of Paediatrics and Child Health, Red Cross War Memorial Children's Hospital and University of Cape Town, South Africa (L.Z., C.H.-H.); Department of Cardiology, All India Institute of Medical Sciences, New Delhi (G.K.); Population Health Research Institute, Hamilton Health Sciences and McMaster University, Ontario, Canada (S.R., P.M., S.I., K.T., S.Y.); Department of Statistical Sciences, University of Cape Town, South Africa (K.M.); Department of Surgery, School of Medicine, College of Health Sciences, University of Nairobi, Kenya (S.O.); Cardiology Unit, Department of Medicine, Kenyatta National Teaching and Referral Hospital, Nairobi, Kenya (B.G.); Cardiology Unit, Department of Medicine, Mulago Hospital, Kampala, Uganda (C.M.); Uganda Heart Institute, Kampala (E.O., P.L.); Faculty of Medicine & Surgery, University of Sana'a, Al-Thawrah Cardiac Center, Yemen (M.M.A.-K.); Paediatric Cardiology Service, Windhoek Central Hospital, Namibia (C.H.-H.); Department of Paediatrics, Division of Paediatric Cardiology, Faculty of Medicine, Cairo University Children's Hospital, Egypt (S.S.S.); Department of Paediatrics and Child Health, Jimma University Hospital, Ethiopia (A.H., W.D.); Department of Internal Medicine, Faculty of Medicine, Addis Ababa, Ethiopia (D.Y.G., S.G.A., A.G.D., B.A.S., D.M.B.); Cardiothoracic Surgery Department, Al Shaab Teaching Hospital and Faculty of Medicine, Alzaiem Alazhari University, Khartoum, Sudan (A.E., A.S.I.); University Teaching Hospital, Department of Paediatrics and Child Health, University of Zambia, Lusaka (J.M.); Departments of Paediatrics and Medicine, Jos University Teaching Hospital, Nigeria (F.B.-T., C.C.Y., G.A.A., O.I., B.O.); Department of Paediatrics and Child Health, University of Limpopo, Polokwane, South Africa (C.S.); Department of Internal Medicine, University of Limpopo, Polokwane, South Africa (R.M.); Faculty of Medicine, Benha University, Cairo, Egypt (A.A.F.); Department of Paediatrics and Child Health, College of Medicine, University of Malawi, Blantyre (N.K.); Department of Medicine, Eduardo Mondlane University, Maputo, Mozambique (A.D.); Department of Medicine, Bayero University and Aminu Kano Teaching Hospital, Nigeria (M.U.S.); Division of Cardiology, Department of Medicine, University College Hospital, Ibadan, Nigeria (O.S.O., A.M.A.); Nigeria Ministry of Health, Umuahia, Abia State (O.S.O.); Department of Medicine, Federal Medical Centre, Abeokuta, Nigeria (O.S.O., T.O.); Ahmed Gasim Teaching Hospital, Khartoum, Sudan (H.H.M.E.); Instituto Nacional de Saúde and Eduardo Mondlane University, Maputo, Mozambique (A.O.M.); Department of Cardiology, Dr. George Mukhari Hospital and Sefako Makgatho Health Sciences University, Tshwane, South Africa (P.M.); Cardiology Unit, Department of Medicine, University of Abuja Teaching Hospital, Nigeria (D.O.); and Paediatric Cardiology Unit, Department of Paediatrics, King Faisal Hospital, Kigali, Rwanda (J.M.).

Background: There are few contemporary data on the mortality and morbidity associated with rheumatic heart disease or information on their predictors. We report the 2-year follow-up of individuals with rheumatic heart disease from 14 low- and middle-income countries in Africa and Asia.

Methods: Between January 2010 and November 2012, we enrolled 3343 patients from 25 centers in 14 countries and followed them for 2 years to assess mortality, congestive heart failure, stroke or transient ischemic attack, recurrent acute rheumatic fever, and infective endocarditis.

Results: Vital status at 24 months was known for 2960 (88.5%) patients. Two-thirds were female. Although patients were young (median age, 28 years; interquartile range, 18-40), the 2-year case fatality rate was high (500 deaths, 16.9%). Mortality rate was 116.3/1000 patient-years in the first year and 65.4/1000 patient-years in the second year. Median age at death was 28.7 years. Independent predictors of death were severe valve disease (hazard ratio [HR], 2.36; 95% confidence interval [CI], 1.80-3.11), congestive heart failure (HR, 2.16; 95% CI, 1.70-2.72), New York Heart Association functional class III/IV (HR, 1.67; 95% CI, 1.32-2.10), atrial fibrillation (HR, 1.40; 95% CI, 1.10-1.78), and older age (HR, 1.02; 95% CI, 1.01-1.02 per year increase) at enrollment. Postprimary education (HR, 0.67; 95% CI, 0.54-0.85) and female sex (HR, 0.65; 95% CI, 0.52-0.80) were associated with lower risk of death. Two hundred and four (6.9%) patients had new congestive heart failure (incidence, 38.42/1000 patient-years), 46 (1.6%) had a stroke or transient ischemic attack (8.45/1000 patient-years), 19 (0.6%) had recurrent acute rheumatic fever (3.49/1000 patient-years), and 20 (0.7%) had infective endocarditis (3.65/1000 patient-years). Previous stroke and older age were independent predictors of stroke/transient ischemic attack or systemic embolism. Patients from low- and lower-middle-income countries had significantly higher age- and sex-adjusted mortality than patients from upper-middle-income countries. Valve surgery was significantly more common in upper-middle-income than in lower-middle- or low-income countries.

Conclusions: Patients with clinical rheumatic heart disease have high mortality and morbidity despite being young; those from low- and lower-middle-income countries had a poorer prognosis associated with advanced disease and low education. Programs focused on early detection and the treatment of clinical rheumatic heart disease are required to improve outcomes.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.116.024769DOI Listing
November 2016

Clinical Outcomes in 3343 Children and Adults With Rheumatic Heart Disease From 14 Low- and Middle-Income Countries: Two-Year Follow-Up of the Global Rheumatic Heart Disease Registry (the REMEDY Study).

Circulation 2016 Nov 4;134(19):1456-1466. Epub 2016 Oct 4.

From Cardiac Clinic, Department of Medicine, Groote Schuur Hospital and University of Cape Town, South Africa (L.Z., M.E.E., B.C., R.D., V.F., B.M.M.); Division of Paediatric Cardiology, Department of Paediatrics and Child Health, Red Cross War Memorial Children's Hospital and University of Cape Town, South Africa (L.Z., C.H.-H.); Department of Cardiology, All India Institute of Medical Sciences, New Delhi (G.K.); Population Health Research Institute, Hamilton Health Sciences and McMaster University, Ontario, Canada (S.R., P.M., S.I., K.T., S.Y.); Department of Statistical Sciences, University of Cape Town, South Africa (K.M.); Department of Surgery, School of Medicine, College of Health Sciences, University of Nairobi, Kenya (S.O.); Cardiology Unit, Department of Medicine, Kenyatta National Teaching and Referral Hospital, Nairobi, Kenya (B.G.); Cardiology Unit, Department of Medicine, Mulago Hospital, Kampala, Uganda (C.M.); Uganda Heart Institute, Kampala (E.O., P.L.); Faculty of Medicine & Surgery, University of Sana'a, Al-Thawrah Cardiac Center, Yemen (M.M.A.-K.); Paediatric Cardiology Service, Windhoek Central Hospital, Namibia (C.H.-H.); Department of Paediatrics, Division of Paediatric Cardiology, Faculty of Medicine, Cairo University Children's Hospital, Egypt (S.S.S.); Department of Paediatrics and Child Health, Jimma University Hospital, Ethiopia (A.H., W.D.); Department of Internal Medicine, Faculty of Medicine, Addis Ababa, Ethiopia (D.Y.G., S.G.A., A.G.D., B.A.S., D.M.B.); Cardiothoracic Surgery Department, Al Shaab Teaching Hospital and Faculty of Medicine, Alzaiem Alazhari University, Khartoum, Sudan (A.E., A.S.I.); University Teaching Hospital, Department of Paediatrics and Child Health, University of Zambia, Lusaka (J.M.); Departments of Paediatrics and Medicine, Jos University Teaching Hospital, Nigeria (F.B.-T., C.C.Y., G.A.A., O.I., B.O.); Department of Paediatrics and Child Health, University of Limpopo, Polokwane, South Africa (C.S.); Department of Internal Medicine, University of Limpopo, Polokwane, South Africa (R.M.); Faculty of Medicine, Benha University, Cairo, Egypt (A.A.F.); Department of Paediatrics and Child Health, College of Medicine, University of Malawi, Blantyre (N.K.); Department of Medicine, Eduardo Mondlane University, Maputo, Mozambique (A.D.); Department of Medicine, Bayero University and Aminu Kano Teaching Hospital, Nigeria (M.U.S.); Division of Cardiology, Department of Medicine, University College Hospital, Ibadan, Nigeria (O.S.O., A.M.A.); Nigeria Ministry of Health, Umuahia, Abia State (O.S.O.); Department of Medicine, Federal Medical Centre, Abeokuta, Nigeria (O.S.O., T.O.); Ahmed Gasim Teaching Hospital, Khartoum, Sudan (H.H.M.E.); Instituto Nacional de Saúde and Eduardo Mondlane University, Maputo, Mozambique (A.O.M.); Department of Cardiology, Dr. George Mukhari Hospital and Sefako Makgatho Health Sciences University, Tshwane, South Africa (P.M.); Cardiology Unit, Department of Medicine, University of Abuja Teaching Hospital, Nigeria (D.O.); and Paediatric Cardiology Unit, Department of Paediatrics, King Faisal Hospital, Kigali, Rwanda (J.M.).

Background: There are few contemporary data on the mortality and morbidity associated with rheumatic heart disease or information on their predictors. We report the 2-year follow-up of individuals with rheumatic heart disease from 14 low- and middle-income countries in Africa and Asia.

Methods: Between January 2010 and November 2012, we enrolled 3343 patients from 25 centers in 14 countries and followed them for 2 years to assess mortality, congestive heart failure, stroke or transient ischemic attack, recurrent acute rheumatic fever, and infective endocarditis.

Results: Vital status at 24 months was known for 2960 (88.5%) patients. Two-thirds were female. Although patients were young (median age, 28 years; interquartile range, 18-40), the 2-year case fatality rate was high (500 deaths, 16.9%). Mortality rate was 116.3/1000 patient-years in the first year and 65.4/1000 patient-years in the second year. Median age at death was 28.7 years. Independent predictors of death were severe valve disease (hazard ratio [HR], 2.36; 95% confidence interval [CI], 1.80-3.11), congestive heart failure (HR, 2.16; 95% CI, 1.70-2.72), New York Heart Association functional class III/IV (HR, 1.67; 95% CI, 1.32-2.10), atrial fibrillation (HR, 1.40; 95% CI, 1.10-1.78), and older age (HR, 1.02; 95% CI, 1.01-1.02 per year increase) at enrollment. Postprimary education (HR, 0.67; 95% CI, 0.54-0.85) and female sex (HR, 0.65; 95% CI, 0.52-0.80) were associated with lower risk of death. Two hundred and four (6.9%) patients had new congestive heart failure (incidence, 38.42/1000 patient-years), 46 (1.6%) had a stroke or transient ischemic attack (8.45/1000 patient-years), 19 (0.6%) had recurrent acute rheumatic fever (3.49/1000 patient-years), and 20 (0.7%) had infective endocarditis (3.65/1000 patient-years). Previous stroke and older age were independent predictors of stroke/transient ischemic attack or systemic embolism. Patients from low- and lower-middle-income countries had significantly higher age- and sex-adjusted mortality than patients from upper-middle-income countries. Valve surgery was significantly more common in upper-middle-income than in lower-middle- or low-income countries.

Conclusions: Patients with clinical rheumatic heart disease have high mortality and morbidity despite being young; those from low- and lower-middle-income countries had a poorer prognosis associated with advanced disease and low education. Programs focused on early detection and the treatment of clinical rheumatic heart disease are required to improve outcomes.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.116.024769DOI Listing
November 2016

Clinical Outcomes in 3343 Children and Adults With Rheumatic Heart Disease From 14 Low- and Middle-Income Countries: Two-Year Follow-Up of the Global Rheumatic Heart Disease Registry (the REMEDY Study).

Circulation 2016 Nov 4;134(19):1456-1466. Epub 2016 Oct 4.

From Cardiac Clinic, Department of Medicine, Groote Schuur Hospital and University of Cape Town, South Africa (L.Z., M.E.E., B.C., R.D., V.F., B.M.M.); Division of Paediatric Cardiology, Department of Paediatrics and Child Health, Red Cross War Memorial Children's Hospital and University of Cape Town, South Africa (L.Z., C.H.-H.); Department of Cardiology, All India Institute of Medical Sciences, New Delhi (G.K.); Population Health Research Institute, Hamilton Health Sciences and McMaster University, Ontario, Canada (S.R., P.M., S.I., K.T., S.Y.); Department of Statistical Sciences, University of Cape Town, South Africa (K.M.); Department of Surgery, School of Medicine, College of Health Sciences, University of Nairobi, Kenya (S.O.); Cardiology Unit, Department of Medicine, Kenyatta National Teaching and Referral Hospital, Nairobi, Kenya (B.G.); Cardiology Unit, Department of Medicine, Mulago Hospital, Kampala, Uganda (C.M.); Uganda Heart Institute, Kampala (E.O., P.L.); Faculty of Medicine & Surgery, University of Sana'a, Al-Thawrah Cardiac Center, Yemen (M.M.A.-K.); Paediatric Cardiology Service, Windhoek Central Hospital, Namibia (C.H.-H.); Department of Paediatrics, Division of Paediatric Cardiology, Faculty of Medicine, Cairo University Children's Hospital, Egypt (S.S.S.); Department of Paediatrics and Child Health, Jimma University Hospital, Ethiopia (A.H., W.D.); Department of Internal Medicine, Faculty of Medicine, Addis Ababa, Ethiopia (D.Y.G., S.G.A., A.G.D., B.A.S., D.M.B.); Cardiothoracic Surgery Department, Al Shaab Teaching Hospital and Faculty of Medicine, Alzaiem Alazhari University, Khartoum, Sudan (A.E., A.S.I.); University Teaching Hospital, Department of Paediatrics and Child Health, University of Zambia, Lusaka (J.M.); Departments of Paediatrics and Medicine, Jos University Teaching Hospital, Nigeria (F.B.-T., C.C.Y., G.A.A., O.I., B.O.); Department of Paediatrics and Child Health, University of Limpopo, Polokwane, South Africa (C.S.); Department of Internal Medicine, University of Limpopo, Polokwane, South Africa (R.M.); Faculty of Medicine, Benha University, Cairo, Egypt (A.A.F.); Department of Paediatrics and Child Health, College of Medicine, University of Malawi, Blantyre (N.K.); Department of Medicine, Eduardo Mondlane University, Maputo, Mozambique (A.D.); Department of Medicine, Bayero University and Aminu Kano Teaching Hospital, Nigeria (M.U.S.); Division of Cardiology, Department of Medicine, University College Hospital, Ibadan, Nigeria (O.S.O., A.M.A.); Nigeria Ministry of Health, Umuahia, Abia State (O.S.O.); Department of Medicine, Federal Medical Centre, Abeokuta, Nigeria (O.S.O., T.O.); Ahmed Gasim Teaching Hospital, Khartoum, Sudan (H.H.M.E.); Instituto Nacional de Saúde and Eduardo Mondlane University, Maputo, Mozambique (A.O.M.); Department of Cardiology, Dr. George Mukhari Hospital and Sefako Makgatho Health Sciences University, Tshwane, South Africa (P.M.); Cardiology Unit, Department of Medicine, University of Abuja Teaching Hospital, Nigeria (D.O.); and Paediatric Cardiology Unit, Department of Paediatrics, King Faisal Hospital, Kigali, Rwanda (J.M.).

Background: There are few contemporary data on the mortality and morbidity associated with rheumatic heart disease or information on their predictors. We report the 2-year follow-up of individuals with rheumatic heart disease from 14 low- and middle-income countries in Africa and Asia.

Methods: Between January 2010 and November 2012, we enrolled 3343 patients from 25 centers in 14 countries and followed them for 2 years to assess mortality, congestive heart failure, stroke or transient ischemic attack, recurrent acute rheumatic fever, and infective endocarditis.

Results: Vital status at 24 months was known for 2960 (88.5%) patients. Two-thirds were female. Although patients were young (median age, 28 years; interquartile range, 18-40), the 2-year case fatality rate was high (500 deaths, 16.9%). Mortality rate was 116.3/1000 patient-years in the first year and 65.4/1000 patient-years in the second year. Median age at death was 28.7 years. Independent predictors of death were severe valve disease (hazard ratio [HR], 2.36; 95% confidence interval [CI], 1.80-3.11), congestive heart failure (HR, 2.16; 95% CI, 1.70-2.72), New York Heart Association functional class III/IV (HR, 1.67; 95% CI, 1.32-2.10), atrial fibrillation (HR, 1.40; 95% CI, 1.10-1.78), and older age (HR, 1.02; 95% CI, 1.01-1.02 per year increase) at enrollment. Postprimary education (HR, 0.67; 95% CI, 0.54-0.85) and female sex (HR, 0.65; 95% CI, 0.52-0.80) were associated with lower risk of death. Two hundred and four (6.9%) patients had new congestive heart failure (incidence, 38.42/1000 patient-years), 46 (1.6%) had a stroke or transient ischemic attack (8.45/1000 patient-years), 19 (0.6%) had recurrent acute rheumatic fever (3.49/1000 patient-years), and 20 (0.7%) had infective endocarditis (3.65/1000 patient-years). Previous stroke and older age were independent predictors of stroke/transient ischemic attack or systemic embolism. Patients from low- and lower-middle-income countries had significantly higher age- and sex-adjusted mortality than patients from upper-middle-income countries. Valve surgery was significantly more common in upper-middle-income than in lower-middle- or low-income countries.

Conclusions: Patients with clinical rheumatic heart disease have high mortality and morbidity despite being young; those from low- and lower-middle-income countries had a poorer prognosis associated with advanced disease and low education. Programs focused on early detection and the treatment of clinical rheumatic heart disease are required to improve outcomes.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.116.024769DOI Listing
November 2016

A massive open online course (MOOC) can be used to teach physiotherapy students about spinal cord injuries: a randomised trial.

J Physiother 2015 Jan 11;61(1):21-7. Epub 2014 Dec 11.

John Walsh Centre for Rehabilitation Research, Kolling Institute, Sydney Medical School/Northern, University of Sydney, Australia.

Question: Does a massive open online course (MOOC) based around an online learning module about spinal cord injuries improve knowledge or confidence among physiotherapy students more than if physiotherapy students are left to work through the online learning module at their own pace. Which method of presenting the content leads to greater satisfaction among the students?

Study Design: Randomised controlled trial with concealed allocation and intention-to-treat analysis.

Participants: Forty-eight physiotherapy students in Bangladesh.

Intervention: Participants randomised to the control group were instructed to work at their own pace over a 5-week period through a physiotherapy-specific online learning module available at www.elearnSCI.org. Experimental participants were enrolled in a 5-week MOOC. The MOOC involved completing the same online learning module but experimental participants' progress through the module was guided each week and they were provided with the opportunity to engage in online discussion through Facebook.

Outcome Measures: The primary outcome was knowledge, and the secondary outcomes were perceived confidence to treat people with spinal cord injuries and satisfaction with the learning experience.

Results: The mean between-group difference for knowledge was 0.7 points (95% CI -1.3 to 2.6) on a 0 to 20-point scale. The equivalent results for perceived confidence and satisfaction with the learning experience were 0.4 points (95% CI -1.0 to 1.8) and 0.0 points (95% CI -1.1 to 1.2) on a 0 to 10-point scale.

Conclusion: The MOOC was no better for students than working at their own pace through an online learning module for increasing knowledge, confidence or satisfaction. However, students in the MOOC group highlighted positive aspects of the course that were unique to their group, such as interacting with students from other countries through the MOOC Facebook group.

Trial Registration: ACTRN12614000422628.
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http://dx.doi.org/10.1016/j.jphys.2014.09.008DOI Listing
January 2015

Early cerebral small vessel disease and brain volume, cognition, and gait.

Ann Neurol 2015 Feb;77(2):251-61

Hotchkiss Brain Institute; Department of Clinical Neurosciences; Department of Radiology; Seaman Family Centre, University of Calgary, Calgary, Alberta.

Objective: Decline in cognitive function begins by the 40s, and may be related to future dementia risk. We used data from a community-representative study to determine whether there are age-related differences in simple cognitive and gait tests by the 40s, and whether these differences were associated with covert cerebrovascular disease on magnetic resonance imaging (MRI).

Methods: Between 2010 and 2012, 803 participants aged 40 to 75 years in the Prospective Urban Rural Epidemiological (PURE) study, recruited from prespecified postal code regions centered on 4 Canadian cities, underwent brain MRI and simple tests of cognition and gait as part of a substudy (PURE-MIND).

Results: Mean age was 58 ± 8 years. Linear decreases in performance on the Montreal Cognitive Assessment, Digit Symbol Substitution Test (DSST), and Timed Up and Go test of gait were seen with each age decade from the 40s to the 70s. Silent brain infarcts were observed in 3% of 40- to 49-year-olds, with increasing prevalence up to 18.9% in 70-year-olds. Silent brain infarcts were associated with slower timed gait and lower volume of supratentorial white matter. Higher volume of supratentorial MRI white matter hyperintensity was associated with slower timed gait and worse performance on DSST, and lower volumes of the supratentorial cortex and white matter, and cerebellum.

Interpretation: Covert cerebrovascular disease and its consequences on cognitive and gait performance and brain atrophy are manifest in some clinically asymptomatic persons as early as the 5th decade of life.
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http://dx.doi.org/10.1002/ana.24320DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4338762PMC
February 2015

Characteristics, complications, and gaps in evidence-based interventions in rheumatic heart disease: the Global Rheumatic Heart Disease Registry (the REMEDY study).

Eur Heart J 2015 May 25;36(18):1115-22a. Epub 2014 Nov 25.

The Cardiac Clinic, Department of Medicine, Groote Schuur Hospital and University of Cape Town, J Floor Old Groote Schuur Hospital, Groote Schuur Drive, Observatory 7925, Cape Town, South Africa

Aims: Rheumatic heart disease (RHD) accounts for over a million premature deaths annually; however, there is little contemporary information on presentation, complications, and treatment.

Methods And Results: This prospective registry enrolled 3343 patients (median age 28 years, 66.2% female) presenting with RHD at 25 hospitals in 12 African countries, India, and Yemen between January 2010 and November 2012. The majority (63.9%) had moderate-to-severe multivalvular disease complicated by congestive heart failure (33.4%), pulmonary hypertension (28.8%), atrial fibrillation (AF) (21.8%), stroke (7.1%), infective endocarditis (4%), and major bleeding (2.7%). One-quarter of adults and 5.3% of children had decreased left ventricular (LV) systolic function; 23% of adults and 14.1% of children had dilated LVs. Fifty-five percent (n = 1761) of patients were on secondary antibiotic prophylaxis. Oral anti-coagulants were prescribed in 69.5% (n = 946) of patients with mechanical valves (n = 501), AF (n = 397), and high-risk mitral stenosis in sinus rhythm (n = 48). However, only 28.3% (n = 269) had a therapeutic international normalized ratio. Among 1825 women of childbearing age (12-51 years), only 3.6% (n = 65) were on contraception. The utilization of valvuloplasty and valve surgery was higher in upper-middle compared with lower-income countries.

Conclusion: Rheumatic heart disease patients were young, predominantly female, and had high prevalence of major cardiovascular complications. There is suboptimal utilization of secondary antibiotic prophylaxis, oral anti-coagulation, and contraception, and variations in the use of percutaneous and surgical interventions by country income level.
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http://dx.doi.org/10.1093/eurheartj/ehu449DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4422972PMC
May 2015

Cardiovascular risk and events in 17 low-, middle-, and high-income countries.

N Engl J Med 2014 08;371(9):818-27

From the Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, ON (S.Y., S.R., K.T., S.I., S.A., M. McQueen), Department of Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, BC (S.L.), the Department of Medicine, University of Ottawa, Ottawa, ON (A.W.), and Laval University Heart and Lungs Institute, Quebec City, QC (G.D.) - all in Canada; the National Center for Cardiovascular Diseases, Cardiovascular Institute and Fuwai Hospital, Chinese Academy of Medical Sciences, Beijing (W.L., L.L., J.B.), Jiangsu Province Institute of Geriatrics, Jiangsu Province, Nanjing City (Q.L.), Shandong Province Academy of Medical Science, Shandong Province, Jinan City (F. Lu), Xi'an Electronic Technology University Hospital, Shanxi Province, Xi'an City (T.L.), Shenyang City 242 Hospital, Liaoning Province, Shenyang City, Huanggu District (L.Y.), Bayannaoer Center for Disease Control and Prevention, Inner Mongolia, Bayannaoer City, Linhe District, Jiefangxi (S.Z.) - all in China; the Division of Epidemiology and Population Health, St. John's Research Institute, Bangalore (P.M., S.S.), Madras Diabetes Research Foundation, Chennai (V.M.), Fortis Escorts Hospitals, JLN Marg, Jaipur (R.G.), Postgraduate Institute of Medical Education and Research School of Public Health, Chandigarh (R. Kumar), and Health Action by People, Trivandrum, Kerala (K.V.) - all in India; Estudios Clinicos Latinoamerica ECLA, Rosario, Santa Fe, Argentina (R.D.); Dante Pazzanese Institute of Cardiology, São Paulo (A.A.); Fundacion Oftalmologica de Santander (FOSCAL), Medical School, Universidad de Santander, Floridablanca-Santander, Colombia (P.L.-J.); Universidad de La Frontera, Temuco, Chile (F. Lanas); Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh, Selangor, and UCSI University Kuala Lumpur, Kuala Lumpur (K.Y.), and the Department of Community Health, University Kebangsaan Malaysia Medical Centre, Kuala Lumpur (N.I.) - all in Malay

Background: More than 80% of deaths from cardiovascular disease are estimated to occur in low-income and middle-income countries, but the reasons are unknown.

Methods: We enrolled 156,424 persons from 628 urban and rural communities in 17 countries (3 high-income, 10 middle-income, and 4 low-income countries) and assessed their cardiovascular risk using the INTERHEART Risk Score, a validated score for quantifying risk-factor burden without the use of laboratory testing (with higher scores indicating greater risk-factor burden). Participants were followed for incident cardiovascular disease and death for a mean of 4.1 years.

Results: The mean INTERHEART Risk Score was highest in high-income countries, intermediate in middle-income countries, and lowest in low-income countries (P<0.001). However, the rates of major cardiovascular events (death from cardiovascular causes, myocardial infarction, stroke, or heart failure) were lower in high-income countries than in middle- and low-income countries (3.99 events per 1000 person-years vs. 5.38 and 6.43 events per 1000 person-years, respectively; P<0.001). Case fatality rates were also lowest in high-income countries (6.5%, 15.9%, and 17.3% in high-, middle-, and low-income countries, respectively; P=0.01). Urban communities had a higher risk-factor burden than rural communities but lower rates of cardiovascular events (4.83 vs. 6.25 events per 1000 person-years, P<0.001) and case fatality rates (13.52% vs. 17.25%, P<0.001). The use of preventive medications and revascularization procedures was significantly more common in high-income countries than in middle- or low-income countries (P<0.001).

Conclusions: Although the risk-factor burden was lowest in low-income countries, the rates of major cardiovascular disease and death were substantially higher in low-income countries than in high-income countries. The high burden of risk factors in high-income countries may have been mitigated by better control of risk factors and more frequent use of proven pharmacologic therapies and revascularization. (Funded by the Population Health Research Institute and others.).
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http://dx.doi.org/10.1056/NEJMoa1311890DOI Listing
August 2014