Publications by authors named "Henrik Schirmer"

113 Publications

Adherence to prescription guidelines and achievement of treatment goals among persons with coronary heart disease in Tromsø 7.

BMC Cardiovasc Disord 2021 Jan 21;21(1):44. Epub 2021 Jan 21.

Department of Pharmacy, UiT The Arctic University of Norway, Tromsø, Norway.

Background: Adherence to clinical practice guidelines for coronary heart disease (CHD) reduces morbidity, mortality and treatment costs. We aimed to describe and compare adherence to prescription guidelines for persons with CHD, and explore its association with treatment goal achievement.

Method: We included all participants reporting myocardial infarction, angina, percutaneous coronary intervention and/or coronary artery bypass surgery in the seventh wave of the Tromsø Study (2015-2016, n = 1483). Medication use and treatment goal measures (blood pressure, low-density lipoprotein (LDL)-cholesterol and HbA1c) were compared to clinical practice guidelines on secondary CHD prevention. Propensity score matched logistic regression was used to assess the association between the use of antihypertensive drugs and achievement of treatment goal for blood pressure, and the use of lipid-lowering drugs (LLDs) and achievement of treatment goal for LDL-cholesterol.

Results: The prevalence of pharmacological CHD treatment was 76% for LLDs, 72% for antihypertensive drugs and 66% for acetylsalicylic acid. The blood pressure goal (< 140/90 mmHg, < 140/80 mmHg if diabetic) was achieved by 58% and the LDL-cholesterol goal (< 1.8 mmol/l or < 70 mg/dL) by 9%. There was a strong association between using LLDs and achieving the treatment goal for LDL-cholesterol (OR 14.0, 95% CI 3.6-54.7), but not between using antihypertensive drugs and blood pressure goal achievement (OR 1.4, 95% CI 0.7-2.7).

Conclusion: Treatment goal achievement of LDL-cholesterol and blood pressure was low, despite the relatively high use of LLDs and antihypertensive drugs. Further research is needed to find the proper actions to increase achievement of the treatment goals.
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http://dx.doi.org/10.1186/s12872-021-01866-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7819182PMC
January 2021

Cross-sectional associations between accelerometry-measured physical activity, left atrial size, and indices of left ventricular diastolic dysfunction: The Tromsø Study.

Prev Med Rep 2021 Mar 31;21:101290. Epub 2020 Dec 31.

School of Sport Sciences, UiT The Arctic University of Norway, Tromsø, Norway.

Whereas left atrial (LA) enlargement is an independent predictor for adverse cardiovascular events and all-cause mortality, this is regarded a physiological adaption of exercise. Paradoxically, LA size in athletes may overlap the enlargement observed in patients with cardiac pathology. Current knowledge is mainly derived from studies of athletes, and little is known about cardiac adaptations to physical activity (PA) in the general population. We explored the association between objectively measured PA and LA volume index (LAVi), and between LAVi enlargement and indices of diastolic dysfunction stratified by PA-level. Our study included 1573 participants from the population-based Tromsø Study (2015-16). PA was assessed with an ActiGraph wGT3X-BT accelerometer. Echocardiography was performed according to current guidelines. The associations between PA and LAVi, and between LAVi enlargement and indices of diastolic dysfunction were estimated by univariable and multivariable linear regression analyses, adjusted for sex, age, and cardiovascular risk factors. Our multiple adjusted analyses showed significant linear associations between PA and LAVi in ages < 70 years, and between PA and LAVi in participants with normal diastolic function. No associations were seen in ages ≥ 70 years or for participants with abnormal diastolic function. In those 40-54 years, the most active participants had larger LAVi (4.45 mL/m, p = 0.016) than the least active. LAVi enlargement was only associated with indices of diastolic dysfunction in the most inactive participants. In conclusion, higher levels of PA associate with greater LAVi in participants < 70 years with normal diastolic function. LAVi enlargement is only associated with diastolic dysfunction in the most inactive participants.
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http://dx.doi.org/10.1016/j.pmedr.2020.101290DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7782323PMC
March 2021

External validation of a deep learning electrocardiogram algorithm to detect ventricular dysfunction.

Int J Cardiol 2021 Apr 2;329:130-135. Epub 2021 Jan 2.

Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN, USA. Electronic address:

Objective: To validate a novel artificial-intelligence electrocardiogram algorithm (AI-ECG) to detect left ventricular systolic dysfunction (LVSD) in an external population.

Background: LVSD, even when asymptomatic, confers increased morbidity and mortality. We recently derived AI-ECG to detect LVSD using ECGs based on a large sample of patients treated at the Mayo Clinic.

Methods: We performed an external validation study with subjects from the Know Your Heart Study, a cross-sectional study of adults aged 35-69 years residing in two cities in Russia, who had undergone both ECG and transthoracic echocardiography. LVSD was defined as left ventricular ejection fraction ≤ 35%. We assessed the performance of the AI-ECG to identify LVSD in this distinct patient population.

Results: Among 4277 subjects in this external population-based validation study, 0.6% had LVSD (compared to 7.8% of the original clinical derivation study). The overall performance of the AI-ECG to detect LVSD was robust with an area under the receiver operating curve of 0.82. When using the LVSD probability cut-off of 0.256 from the original derivation study, the sensitivity, specificity, and accuracy in this population were 26.9%, 97.4%, 97.0%, respectively. Other probability cut-offs were analysed for different sensitivity values.

Conclusions: The AI-ECG detected LVSD with robust test performance in a population that was very different from that used to develop the algorithm. Population-specific cut-offs may be necessary for clinical implementation. Differences in population characteristics, ECG and echocardiographic data quality may affect test performance.
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http://dx.doi.org/10.1016/j.ijcard.2020.12.065DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955278PMC
April 2021

A possible effect of montelukast on neurological aging examined by the use of register data.

Int J Clin Pharm 2020 Oct 9. Epub 2020 Oct 9.

Division of Mental and Physical Health, Norwegian Institute of Public Health, Oslo, Norway.

Background The leukotriene receptor antagonist montelukast has been shown to rejuvenate aged brains in rats; however, data on humans are still scarce. Objective To investigate if montelukast may alleviate degenerative neurological changes using a register data. Setting Norwegian registry data analyses. Method The present observational study was based on data from the Norwegian Prescription Database and the Tromsø Study. The former has information regarding the use of prescription medicine; the latter includes tests for brain function such as subjective memory and finger-tapping. Multivariate linear regression analyses were performed to see how the use of various medications correlated with the test results, correcting for likely confounders. Main outcome measure Results on seven different tests considered relevant for neurological health were used as outcome. Results Previous use of montelukast correlated with improved scores on cognitive or neurological functioning (F = 2.20, p = 0.03 in a multivariate test). A range of other medications were tested with the same algorithm, including drugs acting on the immune system, but none of them correlated with (overall) significantly improved test results. Conclusion The present data suggest that montelukast may alleviate degenerative neurological changes associated with human aging.
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http://dx.doi.org/10.1007/s11096-020-01160-8DOI Listing
October 2020

Prediction of chronic heart failure and chronic obstructive pulmonary disease in a general population: the Tromsø study.

ESC Heart Fail 2020 Oct 7. Epub 2020 Oct 7.

Campus Ahus, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.

Aims: Heart failure (HF) and chronic obstructive pulmonary disease (COPD) are main causes of dyspnoea, and echocardiography and spirometry are essential investigations for these diagnoses. Our aim was to determine the prevalence of HF and COPD in a general population, also how the diseases may be identified, and to what extent their clinical characteristics differ.

Methods And Results: In the seventh survey of Tromsø study (2015-16), subjects aged 40 years or more were examined with echocardiography, spirometry, lung sound recordings, questionnaires, including the modified Medical Research Council (mMRC) questionnaire on dyspnoea, and N-terminal pro-brain natriuretic peptide analysis. A diagnosis of HF (HF with reduced ejection fraction, HF with mid-range ejection fraction, or HF with preserved ejection fraction) or COPD was established according to current guidelines. Predictors of HF and COPD were evaluated by logistic regression and receiver operating characteristic curve analysis. A total of 7110 participants could be evaluated for COPD, 1624 for HF, and 1538 for both diseases. Age-standardized prevalence of HF was 6.8% for women and 6.1% for men; the respective figures for COPD were 5.2% and 5.1%. Among the 1538 evaluated for both diseases, 139 subjects fulfilled the HF criteria, but only 17.1% reported to have the disease. Of those fulfilling the COPD criteria, 31.6% reported to have the disease. Shortness of breath at exertion was a frequent finding in HF; 59% of those with mMRC ≥2 had HF, while such shortness of breath was found in 24% among those with COPD. Reporting mMRC ≥2 had an odds ratio for HF of 19.5 (95% confidence interval 11.3-33.7), whereas the odds ratio for COPD was 6.3 (95% confidence interval 3.5-11.6). Current smoking was the strongest predictor of COPD but did not predict HF. Basal inspiratory crackles were significant predictors of HF in multivariable analysis. Among the subtypes of HF, an age <70 years was most frequently found in HF with reduced ejection fraction, in 51.7%. Clinical scores based on the predictive value in multivariable analysis of history, symptoms, and signs predicted HF and COPD with areas under the curve of 0.833 and 0.829, respectively.

Conclusions: Study participants with HF and COPD were in most cases not aware of their condition. In general practice, when an elderly patient present with shortness of breath, both diseases should be considered. Previous cardiovascular disease points at HF, while a history of smoking points at COPD. The threshold should be low for ordering echocardiography or spirometry for verifying the suspected cause of dyspnoea.
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http://dx.doi.org/10.1002/ehf2.13035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7754893PMC
October 2020

Cardiovascular Hospitalizations, Influenza Activity, and COVID-19 Measures.

Circulation 2020 09 6;142(13):1302-1304. Epub 2020 Aug 6.

Department of Cardiology, Division of Medicine, Akershus University Hospital, Lørenskog, Norway (P.L.M., I.G., T.O., H.S.).

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http://dx.doi.org/10.1161/CIRCULATIONAHA.120.049118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7515472PMC
September 2020

Pharmacological management of modifiable cardiovascular risk factors (blood pressure and lipids) following diagnosis of myocardial infarction, stroke and diabetes: comparison between population-based studies in Russia and Norway.

BMC Cardiovasc Disord 2020 05 19;20(1):234. Epub 2020 May 19.

Department of Community Medicine, UiT The Arctic University of Norway, 9037, Tromsø, Norway.

Background: Cardiovascular disease (CVD) mortality is substantially higher in Russia than in neighbouring Norway. We aimed to compare blood pressure- and lipid-lowering medication use and proportion meeting treatment targets between general population samples in the two countries in those with CVD and diabetes.

Methods: The study population was adults aged 40-69 years reporting a diagnosis of myocardial infarction (MI), stroke and/or diabetes participating in cross-sectional population-based studies in Russia (Know Your Heart (KYH) 2015-18 N = 626) and Norway (The Tromsø Study 2015-16 (Tromsø 7) N = 1353). Reported medications were coded according to the 2016 WHO Anatomical Therapeutic Chemical Classification system. Treatment targets were defined using the Joint European Societies guidelines for CVD prevention in clinical practice (2016).

Results: Age- and sex-standardized prevalence of use of lipid-lowering medications was higher in Tromsø 7 for all three conditions with a disproportionately large difference in those reporting MI (+ 48% (95% CI 39, 57%)). Proportion meeting treatment targets for LDL cholesterol was poor in both studies (age- and sex-standardized prevalence of control KYH vs Tromsø 7: MI 5.1% vs 10.1%; stroke 11.6% vs 5.8%; diabetes 24.9% vs 23.3%). Use of antihypertensive medication was higher in KYH for stroke (+ 40% (95% CI 30, 50%)) and diabetes (+ 27% (95% CI 19, 34%)) groups but approximately equal for the MI group (- 1% (95% CI -1, 1%)). Proportion meeting blood pressure targets was lower in KYH vs Tromsø 7 (MI 51.8% vs 76.3%; stroke 49.5% vs 69.6%; diabetes 51.9% vs 63.9%).

Conclusions: We identified different patterns of medication use in people with CVD and diabetes. However despite higher use of lipid-lowering medication in the Norwegian study treatment to target for total cholesterol was poor in both Russian and Norwegian studies. In contrast we found higher levels of use of antihypertensive medications in the Russian study but also that less participants met treatment targets for blood pressure. Further work should investigate what factors are responsible for this seeming paradox and how management of modifiable risk factors for secondary prevention could be improved.
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http://dx.doi.org/10.1186/s12872-020-01513-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7236339PMC
May 2020

Why does Russia have such high cardiovascular mortality rates? Comparisons of blood-based biomarkers with Norway implicate non-ischaemic cardiac damage.

J Epidemiol Community Health 2020 09 15;74(9):698-704. Epub 2020 May 15.

Department of Community Medicine, UiT the Arctic University of Norway, Tromsø, Norway.

Background: Russia has one of the highest rates of mortality from cardiovascular disease (CVD). At age 35-69 years, they are eight times higher than in neighbouring Norway. Comparing profiles of blood-based CVD biomarkers between these two populations can help identify reasons for this substantial difference in risk.

Methods: We compared age-standardised mean levels of CVD biomarkers for men and women aged 40-69 years measured in two cross-sectional population-based studies: Know Your Heart (KYH) (Russia, 2015-2018; n=4046) and the seventh wave of the Tromsø Study (Tromsø 7) (Norway, 2015-2018; n=17 646). A laboratory calibration study was performed to account for inter-laboratory differences.

Results: Levels of total, low-density lipoprotein-, high-density lipoprotein-cholesterol and triglycerides were comparable in KYH and Tromsø 7 studies. N-terminal pro-b-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin T (hs-cTnT) and high-sensitivity C-reactive protein (hsCRP) were higher in KYH compared with Tromsø 7 (NT-proBNP was higher by 54.1% (95% CI 41.5% to 67.8%) in men and by 30.8% (95% CI 22.9% to 39.2%) in women; hs-cTnT-by 42.4% (95% CI 36.1% to 49.0%) in men and by 68.1% (95% CI 62.4% to 73.9%) in women; hsCRP-by 33.3% (95% CI 26.1% to 40.8%) in men and by 35.6% (95% CI 29.0% to 42.6%) in women). Exclusion of participants with pre-existing coronary heart disease (279 men and 282 women) had no substantive effect.

Conclusions: Differences in cholesterol fractions cannot explain the difference in CVD mortality rate between Russia and Norway. A non-ischemic pathway to the cardiac damage reflected by raised NT-proBNP and hs-cTnT is likely to contribute to high CVD mortality in Russia.
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http://dx.doi.org/10.1136/jech-2020-213885DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7577103PMC
September 2020

The Effect of Blood Pressure on Cognitive Performance. An 8-Year Follow-Up of the Tromsø Study, Comprising People Aged 45-74 Years.

Front Psychol 2020 21;11:607. Epub 2020 Apr 21.

Norwegian National Advisory Unit on Ageing and Health, Vestfold County Hospital Trust, Tønsberg, Norway.

Background: The relationship between blood pressure (BP) and cognition is complex were age appears to be an intervening variable. High and low BP have been associated with cognitive deficits as part of the aging process, but more studies are needed, especially in more recent birth cohorts.

Methods: The study sample comprised 4,465 participants, with BP measured at baseline in the Tromsø Study, Wave 6 in 2007-2008 (T0), and cognition assessed at follow-up 8 years later, in 2015-2016 in Tromsø Study 7 (T1). Age at T0 was 45-74 years, and at T1 it was 53-82 years. Cognition was assessed with three tests: The Mini Mental State Examination (MMSE), the Digit Symbol Test, and the Twelve-word Test. The associations between BP and cognition were examined specifically for age and sex using linear regression analysis adjusted for baseline BP medication use, education and body mass index (kg/m).

Results: BP was associated with cognition at the 8-year follow-up, but the association differed according to age and sex. In men, higher systolic blood pressure (SBP) and diastolic blood pressure (DBP) at a young age (45-55 years of age) was associated with poorer cognition; the association was reversed at older ages, especially for those above 65 years of age. In women, the associations were generally weaker than for men, and sometimes in the opposite direction: For women, a higher SBP was associated with better cognition at a younger age and higher SBP poorer cognition at older ages - perhaps due to an age delay in women compared to men. Digit Symbol Test results correlated best with BP in a three-way interaction: BP by age by sex was significant for both SBP ( = 0.005) and DBP ( = 0.005).

Conclusion: Increased SBP and DBP at the younger age was clearly associated with poorer cognitive function in men 8 years later; in women the associations were weaker and sometimes in the opposite direction. Our findings clearly indicate that interactions between age and sex related to BP can predict cognitive performance over time. Men and women have different age trajectories regarding the influence of BP on cognition.
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http://dx.doi.org/10.3389/fpsyg.2020.00607DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7186429PMC
April 2020

A prospective study on the effect of self-reported health and leisure time physical activity on mortality among an ageing population: results from the Tromsø study.

BMC Public Health 2020 Apr 28;20(1):575. Epub 2020 Apr 28.

Department of Psychology, Faculty of Health Sciences, UiT - The Arctic University of Norway, Tromsø, Norway.

Background: The prevailing Western ideal of ageing in place, with the option to stay at home as one ages, has led to the development of physical activity guidelines for people of advanced age to increase their quality of life and promote their functional abilities. This study investigates the effect of self-reported health and physical activity on mortality and examines how levels of age-specific physical activity affect self-reported health trajectories in an ageing cohort.

Methods: The sample cohort of the population-based Tromsø Study consists of 24,309 participants aged 25-97 years at baseline. This study involved a survival analysis from 1994 to 2015 and included those who completed two or more surveys (n = 12,241) between 1994 and 2008. The purpose was to examine the relationship between physical activity and self-reported health throughout life using a random coefficient model analysis.

Results: Being sedentary was associated with an increased risk of mortality in the ageing cohort. Subjects who reported neither light physical activity nor hard physical activity had a 57% (OR 1.57, 1.07-2.31) increased risk of all-cause death. Both hard (OR 2.77, 2.35-3.26) and light (OR 1.52, 1.32-1.76) physical activity were positively associated with self-reported health. The effect was age dependent. Vigorous physical activity was most beneficial for individuals younger than 40 years old, while moderate physical activity levels prolonged the period in which good self-reported health was likely.

Conclusions: Poor self-reported health and being sedentary were independently associated with an increased risk of mortality in the participants. Furthermore, physical activity prolonged the period of good self-reported health among older adults in two ways: physical activity habits from early adulthood and onwards were beneficial to self-reported health at an advanced age, and self-reported health was dependent on engagement in moderate intensity physical activity after approximately 65 years of age.
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http://dx.doi.org/10.1186/s12889-020-08681-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7189588PMC
April 2020

Self-reported health as a predictor of mortality: A cohort study of its relation to other health measurements and observation time.

Sci Rep 2020 03 17;10(1):4886. Epub 2020 Mar 17.

UiT The Arctic University of Norway, Tromsø, Norway.

Self-reported health (SRH) is widely used as an epidemiological instrument given the changes in public health since its introduction in the 1980s. We examined the association between SRH and mortality and how this is affected by time and health measurements in a prospective cohort study using repeated measurements and physical examinations of 11652 men and 12684 women in Tromsø, Norway. We used Cox proportional hazard regression to estimate hazard ratios (HRs) of death for SRH, controlling for pathology, biometrics, smoking, sex and age. SRH predicted mortality independently of other, more objective health measures. Higher SRH was strongly associated with lower mortality risk. Poor SRH had HR 2.51 (CI: 2.19, 2.88). SRH is affected by disease, mental health and other risk factors, but these factors had little impact on HRs (Poor SRH: HR 1.99; CI: 1.72, 2.31). SRH predicted mortality, but with a time-dependent effect. Time strongly affected the hazard ratio for mortality, especially after ten-year follow-up (Poor SRH HR 3.63 at 0-5 years decreased to HR 1.58 at 15-21 years). SRH has both methodological and clinical value. It should not be uncritically utilised as a replacement instrument when measures of physical illness and other objective health measures are lacking.
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http://dx.doi.org/10.1038/s41598-020-61603-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7078209PMC
March 2020

Uncontrolled and apparent treatment resistant hypertension: a cross-sectional study of Russian and Norwegian 40-69 year olds.

BMC Cardiovasc Disord 2020 03 13;20(1):135. Epub 2020 Mar 13.

London School of Hygiene & Tropical Medicine, WC1E 7HT, London, UK.

Background: Uncontrolled hypertension is a major cardiovascular risk factor. We examined uncontrolled hypertension and differences in treatment regimens between a high-risk country, Russia, and low-risk Norway to gain better understanding of the underlying factors.

Methods: Population-based survey data on 40-69 year olds with hypertension defined as taking antihypertensives and/or having high blood pressure (140+/90+ mmHg) were obtained from Know Your Heart Study (KYH, N = 2284), Russian Federation (2015-2018) and seventh wave of The Tromsø Study (Tromsø 7, N = 5939), Norway (2015-2016). Uncontrolled hypertension was studied in the subset taking antihypertensives (KYH: N = 1584; Tromsø 7: 2792)and defined as having high blood pressure (140+/90+ mmHg). Apparent treatment resistant hypertension (aTRH) was defined as individuals with uncontrolled hypertension on 3+ OR controlled on 4+ antihypertensive classes in the same subset.

Results: Among all those with hypertension regardless of treatment status, control of blood pressure was achieved in 22% of men (KYH and Tromsø 7), while among women it was 33% in Tromsø 7 and 43% in KYH. When the analysis was limited to those on treatment for hypertension, the percentage uncontrolled was higher in KYH (47.8%, CI 95 44.6-50.9%) than Tromsø 7 (38.2, 36.1-40.5%). The corresponding figures for aTRH were 9.8% (8.2-11.7%) and 5.7% (4.8-6.8%). Antihypertensive monotherapies were more common than combinations and used by 58% in Tromsø 7 and 44% in KYH. In both KYH and Tromsø 7, untreated hypertension was higher in men, those with no GP visit in the past year and problem drinkers. In both studies, aTRH was associated with older age, CVD history, obesity, and diabetes. In Tromsø 7, also male gender and any drinking. In KYH, also chronic kidney disease.

Conclusion: There is considerable scope for promoting combination therapies in line with European treatment guidelines in both study populations. The factors associated with untreated hypertension overlap with known correlates of treatment non-adherence and health check non-attendance. In contrast, aTRH was characterised by obesity and underlying comorbidities potentially complicating treatment.
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http://dx.doi.org/10.1186/s12872-020-01407-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7071707PMC
March 2020

Employment status three years after percutaneous coronary intervention and predictors for being employed: A nationwide prospective cohort study.

Eur J Cardiovasc Nurs 2020 06 28;19(5):433-439. Epub 2020 Feb 28.

Institute of Clinical Medicine, The Arctic University of Norway, Tromsø, Norway.

Background: Vocational support is recommended for patients in cardiac rehabilitation (CR), as returning to work is important in patients social readjusting after an acute coronary event. Information is lacking on whether CR leads to higher long-term employment after percutaneous coronary intervention (PCI).

Aims: The aims of this study were to determine employment status three years after PCI, to compare employment status between CR participants and CR non-participants and to assess predictors for employment.

Methods: We included first-time PCI patients from the NorStent trial, who were of working age (<63 years; = 2488) at a three-year follow-up. Employment status and CR participation were assessed using a self-report questionnaire. Propensity score method was used in comparing employment status of CR participants and CR non-participants.

Results: Seventy per cent of participants who were <60 years of age at the index event were employed at follow-up and CR participation had no effect on employment status. Being male, living with a partner and attaining higher levels of education were associated with a higher chance of being employed, while being older, prior cardiovascular morbidity and smoking status were associated with lower chance of being employed at follow-up.

Conclusion: Because a significant number of working-age coronary heart disease patients are unemployed three years after coronary revascularization, updated incentives should be implemented to promote vocational support. Such programmes should focus on females, patients lacking higher education and patients who are living alone, as they are more likely to remain unemployed.
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http://dx.doi.org/10.1177/1474515120903614DOI Listing
June 2020

Management of patients with acute ST-segment elevation myocardial infarction in Russian hospitals adheres to international guidelines.

Open Heart 2020 23;7(1):e001134. Epub 2020 Jan 23.

Department of Health Services Research and Policy, London School of Hygiene and Tropical Medicine, London, United Kingdom.

Objective: Russia has one of the highest cardiovascular mortality rates. Modernisation of the Russian health system has been accompanied by a substantial increase in uptake of percutaneous coronary intervention (PCI), which substantially reduces the risk of mortality in patients with acute ST-elevation myocardial infarction (STEMI). This paper aims to describe contemporary Hospital treatment of acute STEMI among patients in a range of hospitals in the Russian Federation.

Methods: This study used data from a prospective observational cohort of 1128 suspected patients with myocardial infarction recruited in both PCI and non-PCI hospitals across 13 regions and multiple levels of the health system in Russia. The primary objective was to examine the use of reperfusion strategies in patients with STEMI.

Results: Among patients reaching PCI centres within 12 hours of symptom onset, the vast majority received angiography and PCI, regardless of age, sex and comorbidity, in line with current European Society of Cardiology guidelines.

Conclusion: Patients reaching Russian hospitals are very likely to receive appropriate treatment, although performance varies. The best hospitals can serve as beacons of good practice as PCI facilities continue to expand across Russia where geography allows.
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http://dx.doi.org/10.1136/openhrt-2019-001134DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6999683PMC
June 2020

Global myocardial longitudinal strain in a general population-associations with blood pressure and subclinical heart failure: The Tromsø Study.

Int J Cardiovasc Imaging 2020 Mar 18;36(3):459-470. Epub 2019 Dec 18.

Department of Clinical Medicine, UiT The Arctic University of Norway, Tromsø, Norway.

The early detection of subclinical myocardial dysfunction can contribute to the treatment and prevention of heart failure (HF). The aim of the study was to (i) describe myocardial global longitudinal strain (GLS) patterns in a large general population sample from Norway and their relation to established cardiovascular disease (CVD) risk factors; (ii) to determine its normal thresholds in healthy individuals and (iii) ascertain the relation of myocardial GLS to stage A subclinical heart failure (SAHF). Participants (n = 1855) of the 7th survey of the population-based Tromsø Study of Norway (2015-2016) with GLS measurements were studied. Linear and logistic regression models were used for assessment of the associations between CVD risk factors and GLS. Mean GLS (SD) in healthy participants was - 15.9 (2.7) % in men and - 17.8 (3.1) % in women. Among healthy subjects, defined as those without known cardiovascular diseases and comorbidities, GLS declined with age. An increase of systolic blood pressure (SBP) of 10 mm Hg was associated with a 0.2% GLS reduction. Myocardial GLS in individuals with SAHF was 1.2% lower than in participants without SAHF (p < 0.001). Mean myocardial GLS declines with age in both sexes, both in a general population and in the healthy subsample. SBP increase associated with GLS decline in women. Our findings indicate high sensitivity of GLS for early subclinical stages of HF.
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http://dx.doi.org/10.1007/s10554-019-01741-3DOI Listing
March 2020

Evidence for a Direct Harmful Effect of Alcohol on Myocardial Health: A Large Cross-Sectional Study of Consumption Patterns and Cardiovascular Disease Risk Biomarkers From Northwest Russia, 2015 to 2017.

J Am Heart Assoc 2020 01 18;9(1):e014491. Epub 2019 Dec 18.

Department of Community Medicine UIT The Arctic University of Norway Tromsø Norway.

Background Alcohol drinking is an increasingly recognized risk factor for cardiovascular disease. However, there are few studies of the impact of harmful and hazardous drinking on biomarkers of myocardial health. We conducted a study in Russia to investigate the impact of heavy drinking on biomarkers of cardiac damage and inflammation. Methods and Results The Know Your Heart study recruited a random sample of 2479 participants from the population of northwest Russia (general population) plus 278 patients (narcology clinic subsample) with alcohol problems. The general population sample was categorized into harmful drinkers, hazardous drinkers, nonproblem drinkers, and nondrinkers, according to self-reported level of alcohol consumption, whereas the narcology clinic sample was treated as the separate group in the analysis. Measurements were made of the following: (1) high-sensitivity cardiac troponin T, (2) NT-proBNP (N-terminal pro-B-type natriuretic peptide), and (3) hsCRP (high-sensitivity C-reactive protein). The narcology clinic subsample had the most extreme drinking pattern and the highest levels of all 3 biomarkers relative to nonproblem drinkers in the general population: high-sensitivity cardiac troponin T was elevated by 10.3% (95% CI, 3.7%-17.4%), NT-proBNP by 46.7% (95% CI, 26.8%-69.8%), and hsCRP by 69.2% (95% CI, 43%-100%). In the general population sample, NT-proBNP was 31.5% (95% CI, 3.4%-67.2%) higher among harmful drinkers compared with nonproblem drinkers. Overall, NT-proBNP and hsCRP increased with increasing intensity of alcohol exposure (test of trend <0.001). Conclusions These results support the hypothesis that heavy alcohol drinking has an adverse effect on cardiac structure and function that may not be driven by atherosclerosis.
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http://dx.doi.org/10.1161/JAHA.119.014491DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6988140PMC
January 2020

Neuropsychological functions of verbal recall and psychomotor speed significantly affect pain tolerance.

Eur J Pain 2019 10 29;23(9):1608-1618. Epub 2019 Jul 29.

Department of Pain Management and Research, Division of Emergencies and Critical Care, Oslo University Hospital, Oslo, Norway.

Background: Effects from cognitive performance on pain tolerance have been documented, however, sample sizes are small and confounders often overlooked. We aimed to establish that performance on neuropsychological tests was associated with pain tolerance, controlling for salient confounders.

Methods: This was a cross-sectional study nested within the Tromsø-6 survey. Neuropsychological test performance and the cold pressor test were investigated in 4,623 participants. Due to significant interaction with age, participants were divided into three age groups (<60, ≥60 to <70 and ≥70 years). Cox proportional hazard models assessed the relationship between neuropsychological tests and cold pressure pain tolerance, using hand-withdrawal as event. The fully adjusted models controlled for sex, education, BMI, smoking status, exercise, systolic blood pressure, sleep problems and mental distress.

Results: In the adjusted models, participants aged ≥70 years showed a decreased hazard of hand withdrawal of 18% (HR 0.82, 95% CI (0.73, 0.92) per standard deviation on immediate verbal recall, and a decreased hazard of 23% (HR 0.77, 95% CI (0.65, 0.08) per standard deviation on psychomotor speed. Participants aged ≥60 to <70 years had a significant decreased hazard of 11% (HR 0.89, 95% CI (0.80, 0.98) per standard deviation on immediate word recall. In participants aged <60 years, there was a decreased hazard of 14% (HR 0.86 95% CI: 0.76, 0.98), per standard deviation on psychomotor speed.

Conclusion: Better performance on neuropsychological tests increased pain tolerance on the cold pressor test. These exposure effects were present in all age groups.

Significance: This paper describes substantial associations between cognitive functioning and cold pressor tolerance in 4,623 participants. Reduced psychomotor speed and poor verbal recall gave greater odds for hand-withdrawal on the cold pressor task. The associations were stronger in older participants, indicating an interaction with age.
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http://dx.doi.org/10.1002/ejp.1437DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6790685PMC
October 2019

Predictors of early mortality after transcatheter aortic valve implantation.

Open Heart 2019;6(1):e000936. Epub 2019 Apr 23.

Department of Cardiology, University Hospital of North Norway, Tromsø, Norway.

Objectives: To investigate whether preoperative echocardiographic evaluation of ventricular function, especially right ventricular systolic and diastolic parameters including speckle-tracking analysis, could aid in the prediction of 30-day mortality after transcatheter aortic valve implantation (TAVI) in patients with aortic stenosis.

Methods: This is a prospective observational cohort study including 227 patients accepted for TAVI at the University Hospital of North Norway and Oslo University Hospital from February 2010 through June 2013. All patients underwent preoperative transthoracic echocardiography with retrospective speckle-tracking analysis. Primary endpoint was all-cause 30-day mortality.

Results: All-cause 30-day mortality was 8.7 % (n = 19). Independent predictors of 30-day mortality were systolic pulmonary arterial pressure (SPAP) > 60 mm Hg (HR: 7.7, 95% CI: 1.90 to 31.3), heart failure (HR: 2.9, 95% CI: 1.1 to 7.78), transapical access (HR: 3.8, 95% CI: 1.3 to 11.2), peripheral artery disease (HR: 6.0, 95% CI: 2.0 to 18.0) and body mass index (HR: 0.73, 95% CI: 0.61 to 0.87). C-statistic for the model generated was 0.91 (95% CI: 0.85 to 0.98). Besides elevated SPAP, no other echocardiographic measurements were found to be an independent predictor of early mortality.

Conclusion: Except for elevated systolic pulmonary artery pressure, our data suggests that clinical rather than echocardiographic parameters are useful predictors of 30-day mortality after TAVI.
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http://dx.doi.org/10.1136/openhrt-2018-000936DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6519416PMC
February 2021

Low-grade impairments in cognitive and kidney function in a healthy middle-aged general population: a cross-sectional study.

BMC Nephrol 2019 05 14;20(1):166. Epub 2019 May 14.

Metabolic and Renal Research Group, University in Tromsø (UiT) The Arctic University of Norway, Hansine Hansens veg 18, N-9019, Tromsø, Norway.

Background: Although the relationship between manifest chronic kidney disease and reduced cognitive function is well established, limited data exists on GFR and cognitive function in the general population. Both the brain and kidneys have low-impedance vascular beds, rendering them susceptible to damage from pulsatile blood flow. An association between mildly reduced GFR and cognitive function in the healthy general population may reveal early disease mechanisms underlying low-grade impairment of both organs as well as the possibility for intervention. Our aim was to identify an early stage of low-grade impairments in both the brain and the kidneys in the general population.

Methods: This investigation was a population-based cross-sectional study that included 1627 participants aged 50-62 years who were representative of the general population in the municipality of Tromsø, Norway. The associations between GFR, measured as iohexol clearance, the urinary albumin-creatinine ratio and performance on five tests of cognitive function-the Digit Symbol Substitution Test, the finger tapping test, the Mini-Mental State Examination and the 12-word test parts 1 and 2 - were examined. The data were adjusted for factors known to be associated with both GFR and cognitive function, including cardiovascular risk factors, medications and education level.

Results: In multivariate adjusted linear regression analyses, we did not observe associations of the measured GFR or albumin-creatinine ratio with performance on any of the five cognitive tests. In an analysis without adjustment for the education level, an association of worse performance on the Digit Symbol Substitution Test with higher measured GFR (p = 0.03) was observed. An exploratory analysis revealed an inverse relationship between mGFR and a higher education level that remained significant after adjusting for factors known to influence mGFR.

Conclusions: We did not find evidence of an association between low-grade impairments in either the kidneys or the brain in the middle-aged general population. A possible association between a high GFR and reduced cognitive function should be investigated in future studies.
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http://dx.doi.org/10.1186/s12882-019-1356-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518698PMC
May 2019

Long-term blood pressure trajectories and incident atrial fibrillation in women and men: the Tromsø Study.

Eur Heart J 2020 04;41(16):1554-1562

Department of Community Medicine, UiT The Arctic University of Norway, Hansine Hansens veg 18, 9019 Tromsø, Norway.

Aims: To explore sex-specific associations between long-term individual blood pressure (BP) patterns and risk of incident atrial fibrillation (AF) in the general population.

Methods And Results: Blood pressure was measured in 8376 women and 7670 men who attended at least two of the three population-based Tromsø Study surveys conducted in 1986-87, 1994-95, and 2001. Participants were followed for incident AF throughout 2013. Latent mixed modelling was used to identify long-term trajectories of systolic BP and hypertension. Cox regression was used to estimate associations between the identified trajectories and incident AF. Elevated systolic BP throughout the exposure period (1986-2001) independently and differentially increased risk of AF in women and men. In women, having elevated systolic BP trajectories doubled AF risk compared to having persistently low levels, irrespective of whether systolic BP increased, decreased, or was persistently high over time, with hazard ratios of 1.88 (95% confidence interval 1.37-2.58), 2.32 (1.61-3.35), and 1.94 (1.28-2.94), respectively. In men, those with elevated systolic BP that continued to increase over time had a 50% increased AF risk: 1.51 (1.09-2.10). When compared to those persistently normotensive, women developing hypertension during the exposure period, and women and men with hypertension throughout the exposure period had 1.40 (1.06-1.86), 2.75 (1.99-3.80), and 1.36 (1.10-1.68) times increased risk of AF, respectively.

Conclusion: Long-term BP and hypertension trajectories were associated with increased incidence of AF in both women and men, but the associations were stronger in women.
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http://dx.doi.org/10.1093/eurheartj/ehz234DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7174044PMC
April 2020

Left atrial diameter, left ventricle filling indices, and association with all-cause mortality: Results from the population-based Tromsø Study.

Echocardiography 2019 03 28;36(3):439-450. Epub 2019 Jan 28.

Department of Clinical Medicine, UiT The Arctic University of Norway, Tromsø, Norway.

Aims: To examine the associations between diastolic dysfunction indices and long-term risk of all-cause mortality in adults over 23-year follow-up.

Methods And Results: Participants (n = 2734) of the population-based Tromsø Study of Norway had echocardiography in 1994-1995. Of these 67% were repeated in 2001 and/or 2007-2008. Mortality between 1994 and 2016 was determined by linkage to the national death registry. Cox regression was used to model the hazard of all-cause mortality in relation to left atrial parameters (treated as time-dependent using repeated measurements) adjusted for traditional risk factors and cardiovascular disease. During the follow-up, 1399 participants died. Indexed left atrial diameter, mitral peak E deceleration time, and mitral peak E to peak A ratio showed an U-shaped association with all-cause mortality. Combining left atrial diameter with mitral peak E deceleration time increased the prognostic accuracy for all-cause mortality whereas adding mitral peak E to peak A ratio did not increase prognostic value. We estimated new optimal cutoff values of left atrial diameter, mitral peak E deceleration time, and mitral peak E to peak A ratio for all-cause mortality outcome. E/e' had a cubic relation to mortality.

Conclusion: Both enlarged and small left atrial diameters were associated with increased all-cause mortality risk. A combination of Doppler-based left ventricle filling parameters had an incremental effect on all-cause mortality risk. The cutoff values of diastolic dysfunction indices we determined had similar all-cause mortality prediction ability as those recommended by American Association of Echocardiography and European Association of Cardiovascular Imaging.
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http://dx.doi.org/10.1111/echo.14270DOI Listing
March 2019

Effect of Genetically Low 25-Hydroxyvitamin D on Mortality Risk: Mendelian Randomization Analysis in 3 Large European Cohorts.

Nutrients 2019 Jan 2;11(1). Epub 2019 Jan 2.

Cork Centre for Vitamin D and Nutrition Research, School of Food and Nutritional Sciences, University College Cork, Cork T12K8AF, Ireland.

The aim of this study was to determine if increased mortality associated with low levels of serum 25-hydroxyvitamin D (25(OH)D) reflects a causal relationship by using a Mendelian randomisation (MR) approach with genetic variants in the vitamin D synthesis pathway. Individual participant data from three European cohorts were harmonized with standardization of 25(OH)D according to the Vitamin D Standardization Program. Most relevant single nucleotide polymorphisms of the genes (rs12794714, rs10741657) and (rs12785878, rs11234027), were combined in two allelic scores. Cox proportional hazards regression models were used with the ratio estimator and the delta method for calculating the hazards ratio (HR) and standard error of genetically determined 25(OH)D effect on all-cause mortality. We included 10,501 participants (50.1% females, 67.1±10.1 years) of whom 4003 died during a median follow-up of 10.4 years. The observed adjusted HR for all-cause mortality per decrease in 25(OH)D by 20 nmol/L was 1.20 (95% CI: 1.15⁻1.25). The HR per 20 nmol/L decrease in genetically determined 25(OH)D was 1.32 (95% CI: 0.80⁻2.24) and 1.35 (95% CI of 0.81 to 2.37) based on the two scores. In conclusion, the results of this MR study in a combined sample from three European cohort studies provide further support for a causal relationship between vitamin D deficiency and increased all-cause mortality. However, as the current study, even with ~10,000 participants, was underpowered for the study of the effect of the allele score on mortality, larger studies on genetics and mortality are needed to improve the precision.
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http://dx.doi.org/10.3390/nu11010074DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6356674PMC
January 2019

Know Your Heart: Rationale, design and conduct of a cross-sectional study of cardiovascular structure, function and risk factors in 4500 men and women aged 35-69 years from two Russian cities, 2015-18.

Wellcome Open Res 2018 3;3:67. Epub 2018 Dec 3.

Research Institute of Internal and Preventive Medicine, Branch of Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, 630090, Russian Federation.

Russia has one of the highest rates of cardiovascular disease in the world. The International Project on Cardiovascular Disease in Russia (IPCDR) was set up to understand the reasons for this. A substantial component of this study was the Know Your Heart Study devoted to characterising the nature and causes of cardiovascular disease in Russia by conducting large cross-sectional surveys in two Russian cities Novosibirsk and Arkhangelsk. The study population was 4542 men and women aged 35-69 years recruited from the general population. Fieldwork took place between 2015-18. There were two study components: 1) a baseline interview to collect information on socio-demographic characteristics and cardiovascular risk factors, usually conducted at home, and 2) a comprehensive health check at a primary care clinic which included detailed examination of the cardiovascular system. In this paper we describe in detail the rationale for, design and conduct of these studies.
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http://dx.doi.org/10.12688/wellcomeopenres.14619.3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6073094PMC
December 2018

BEtablocker Treatment After acute Myocardial Infarction in revascularized patients without reduced left ventricular ejection fraction (BETAMI): Rationale and design of a prospective, randomized, open, blinded end point study.

Am Heart J 2019 02 25;208:37-46. Epub 2018 Oct 25.

Department of Cardiology, Oslo University Hospital, Ullevaal and Faculty of Medicine, University of Oslo, Oslo, Norway.

Background: Current guidelines on the use of β-blockers in post-acute myocardial infarction (MI) patients without reduced left ventricular ejection fraction (LVEF) are based on studies before the implementation of modern reperfusion and secondary prevention therapies. It remains unknown whether β-blockers will reduce mortality and recurrent MI in contemporary revascularized post-MI patients without reduced LVEF.

Design: BETAMI is a prospective, randomized, open, blinded end point multicenter study in 10,000 MI patients designed to test the superiority of oral β-blocker therapy compared to no β-blocker therapy. Patients with LVEF ≥40% following treatment with percutaneous coronary intervention or thrombolysis and/or no clinical signs of heart failure are eligible to participate. The primary end point is a composite of all-cause mortality or recurrent MI obtained from national registries over a mean follow-up period of 3 years. Safety end points include rates of nonfatal MI, all-cause mortality, ventricular arrhythmias, and hospitalizations for heart failure obtained from hospital medical records 30 days after randomization, and from national registries after 6 and 18 months. Key secondary end points include recurrent MI, heart failure, cardiovascular and all-cause mortality, and clinical outcomes linked to β-blocker therapy including drug adherence, adverse effects, cardiovascular risk factors, psychosocial factors, and health economy. Statistical analyses will be conducted according to the intention-to-treat principle. A prespecified per-protocol analysis (patients truly on β-blockers or not) will also be conducted.

Conclusions: The results from the BETAMI trial may have the potential of changing current clinical practice for treatment with β-blockers following MI in patients without reduced LVEF. EudraCT number 2018-000590-75.
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http://dx.doi.org/10.1016/j.ahj.2018.10.005DOI Listing
February 2019

Pre-test characteristics of unstable angina patients with obstructive coronary artery disease confirmed by coronary angiography.

Open Heart 2018;5(2):e000888. Epub 2018 Nov 1.

Institute of Clinical Medicine, University of Oslo, Oslo, Norway.

Objective: Patients referred for acute coronary angiography (CAG) with unstable angina (UA) have low mortality and low rate of obstructive coronary artery disease (CAD). Better pre-test selection criteria are warranted. We aimed to assess the current guidelines against other clinical variables as predictors of obstructive CAD in patients with UA referred for acute CAG.

Methods: From 2005 to 2012, all CAGs performed at the University Hospital of North Norway, the sole provider of CAG in the region, were recorded in a registry. We included 979 admissions of UA and retrospectively collected data regarding presenting clinical parameters from patient hospital records. Obstructive CAD was defined as ≥50% stenosis and considered prognostically significant if found in the left main stem, proximal LAD or all three main coronary arteries. Characteristics were analysed by logistic regression analysis. A score was developed using ORs from significant factors in a multivariable model.

Results: The overall rate of obstructive CAD was 45%, and the rate of prognostically significant CAD was 11%. The risk criteria recommended in American College of Cardiology/American Heart Association and European Society of Cardiology guidelines had an area under the curve (AUC) of 0.58. Adding clinical information increased the AUC to 0.77 (95% CI 0.74 to 0.80). Applying the derived score, we found that 56% (n=546) of patients had a score of <13, which was associated with a negative predictive value of 95% for prognostic significant CAD.

Conclusions: The current results suggest that CAG may be postponed or cancelled in more than half of patients with UA by improving pre-test selection criteria with the addition of clinical parameters to current guidelines.
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http://dx.doi.org/10.1136/openhrt-2018-000888DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6241968PMC
November 2018

Office and Ambulatory Heart Rate as Predictors of Age-Related Kidney Function Decline.

Hypertension 2018 09;72(3):594-601

From the Metabolic and Renal Research Group, UiT The Arctic University of Norway, Tromsø (B.O.E., S.S., T.G.J., U.D.M., J.V.N., J.S., M.D.S., V.T.N.S., T.M.).

The decline in glomerular filtration rate (GFR) associated with aging is one of the most important predisposing causes of kidney failure in old age. Identifying persons at risk for accelerated GFR decline is an essential first step in the development of preventive measures to preserve kidney function in the elderly. Heart rate (HR) has not yet been studied as a risk factor for GFR decline in the general population. In the RENIS-T6 (Renal Iohexol-Clearance Survey in Tromsø 6), we measured baseline ambulatory HR and GFR as iohexol clearance in a representative, middle-aged cohort of 1627 persons without self-reported diabetes mellitus, cardiovascular disease, or kidney disease. In the RENIS-FU (RENIS Follow-Up Study), we repeated the GFR measurements and calculated the rate of GFR decline in 81% of the participants after a median follow-up of 5.6 years. The unadjusted mean rate of GFR decline was 0.96 mL/min per year. In multivariable-adjusted linear mixed models, 10 bpm higher ambulatory 24-hour and daytime HRs and office HR were associated with steeper GFR decline rates of 0.20 to 0.21 mL/min per year ( P≤0.01). The odds ratio for predicting a rate of GFR decline twice that of the population mean in a fully adjusted model was 1.24 ( P=0.01) for ambulatory 24-hour HR. Office HR was also an independent predictor of a steeper rate of GFR decline. HR may be a useful biomarker to identify persons at risk of accelerated GFR decline.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.118.11594DOI Listing
September 2018