Publications by authors named "Jorge R Kizer"

204 Publications

Cumulative burden of clinically significant aortic stenosis in community-dwelling older adults.

Heart 2021 Jun 2. Epub 2021 Jun 2.

Cardiology Section, San Francisco VA Health Care System, San Francisco, California, USA

Objectives: Current estimates of aortic stenosis (AS) frequency have mostly relied on cross-sectional echocardiographic or longitudinal administrative data, making understanding of AS burden incomplete. We performed case adjudications to evaluate the frequency of AS and assess differences by age, sex and race in an older cohort with long-term follow-up.

Methods: We developed case-capture methods using study echocardiograms, procedure and diagnosis codes, heart failure events and deaths for targeted review of medical records in the Cardiovascular Health Study to identify moderate or severe AS and related procedures or hospitalisations. The primary outcome was clinically significant AS (severe AS or procedure). Assessment of incident AS burden was based on subdistribution survival methods, while associations with age, sex and race relied on cause-specific survival methods.

Results: The cohort comprised 5795 participants (age 73±6, 42.2% male, 14.3% Black). Cumulative frequency of clinically significant AS at maximal 25-year follow-up was 3.69% (probable/definite) to 4.67% (possible/probable/definite), while the corresponding 20-year cumulative incidence was 2.88% to 3.71%. Of incident cases, about 85% had a hospitalisation for severe AS, but roughly half did not undergo valve intervention. The adjusted incidence of clinically significant AS was higher in men (HR 1.62 [95% CI 1.21 to 2.17]) and increased with age (HR 1.08 [95% CI 1.04 to 1.11]), but was lower in Blacks (HR 0.43 [95% CI 0.23 to 0.81]).

Conclusions: In this community-based study, we identified a higher burden of clinically significant AS than reported previously, with differences by age, sex and race. These findings have important implications for public health resource planning, although the lower burden in Blacks merits further study.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/heartjnl-2021-319025DOI Listing
June 2021

Residual SYNTAX II Score and long-term outcomes post-ST-elevation myocardial infarction in an urban US cohort: the Montefiore STEMI Registry.

Coron Artery Dis 2021 May 26. Epub 2021 May 26.

Department of Medicine, Division of Cardiology Department of Medicine, Division of Geriatrics, Montefiore Medical Center Albert Einstein College of Medicine, Bronx, New York Department of Medicine, Cardiology Section, San Francisco Veterans Affairs Health Care System, and Department of Medicine, University of California San Francisco, San Francisco, California Division of Cardiology, Department of Medicine, MedStar Washington Hospital Center and Georgetown University, Washington DC Sorin Medical, P.C., Brooklyn Division of Cardiovascular Medicine, Department of Medicine, University at Buffalo, Buffalo, New York Department of Anesthesiology, Anesthesiology Institute, Cleveland Clinic, Cleveland, Ohio Department of Medicine, Division of Cardiology, New York Presbyterian Hospital, New York Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California, USA.

Background: Higher residual anatomic disease was associated with increased mortality in a recent randomized controlled trial of revascularization after ST-elevation myocardial infarction (STEMI). Less is known about the impact of residual disease post-STEMI in race-ethnic minorities.

Methods: Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery (SYNTAX)- II (SS-II) score is an established scoring method for anatomic disease and prevalent co-morbidities to describe patient complexity. We evaluated residual (r) SS-II in 165 patients from a single center urban US registry (n = 1208) presenting for primary percutaneous coronary intervention of STEMI and treated for 3-vessel or left main and any combination of 0, 1, 2 or 3-vessel disease.

Results: The median age was 62 years (IQR 52-70), 29.1% women, 44.9% Hispanic/Latino and 19.4% non-Hispanic Black. Over median of 4.9 years (IQR 2.9-6.3), higher rSS-II was associated with increased death [hazard ratio 2.46 per SD increment in log rSS-II (~1.five-fold increment on the original scale) 95% CI 1.51, 3.99], death or all-cause readmission (hazard ratio 1.37 per SD increment in log rSS-II 95% CI, 1.11-1.70) and death or cardiovascular disease readmission (hazard rati 1.46 per SD increment in log rSS-II 95% CI, 1.14-1.88). rSS-II was higher in older women with more co-morbidities, but not different by race-ethnicity.

Conclusions: In summary, higher rSS-II was associated with long-term outcomes post-STEMI in a prospective urban, minority cohort, suggesting a potential role for risk stratification with this measure in a non-trial setting.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MCA.0000000000001074DOI Listing
May 2021

Sleep apnea, coronary artery calcium density and cardiovascular events: results from the Multi-Ethnic Study of Atherosclerosis (MESA).

J Clin Sleep Med 2021 May 14. Epub 2021 May 14.

Icahn School of Medicine at Mount Sinai, New York, NY.

Study Objectives: Evaluate the association between obstructive sleep apnea (OSA), coronary artery calcium (CAC) density, and cardiovascular events in the Multi-Ethnic Study of Atherosclerosis (MESA).

Methods: We analyzed 1041 participants with non-zero CAC scores who had polysomnography and CAC density data from the fifth examination of MESA. OSA was defined as apnea-hypopnea index [AHI] ≥ 15 events/hour. Multivariable linear regression models were used to evaluate the independent association between OSA and CAC density. Additionally, we evaluated the impact of OSA on associations of CAC measures with incident CVD events by testing for interaction in Cox proportional hazard regression models.

Results: Our analytical sample was 45% female with a mean age of 70.6 +/- 9 years. Of this sample, 36.7% (n=383/1041) had OSA (AHI≥15). OSA was inversely and weakly associated with CAC density (β= -0.09, 95% CI -0.17 to -0.02, p=0.014) and remained significantly associated after controlling for traditional cardiovascular risk factors (β= -0.08, 95% CI -0.16 to 0, p=0.043). However, this inverse association was attenuated after controlling for BMI (β=-0.05, 95% CI -0.13 to 0.02, p=0.174). The mean follow-up period for CVD events was 13.3 +/- 2.8 years. Additionally, exploratory analysis demonstrated that CAC density was independently and inversely associated with CVD events only in the non-OSA subgroup (AHI≤15) (HR 0.509 [CI 0.323 - 0.801], p=0.0035).

Conclusions: OSA was associated with lower CAC density, but this association was attenuated by BMI. Further, increased CAC density was associated with a reduced risk of CVD events only in individuals within the non-OSA group in exploratory analysis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5664/jcsm.9356DOI Listing
May 2021

Upregulated IL-32 Expression And Reduced Gut Short Chain Fatty Acid Caproic Acid in People Living With HIV With Subclinical Atherosclerosis.

Front Immunol 2021 15;12:664371. Epub 2021 Apr 15.

University of Montreal Hospital Centre (CRCHUM)-Research Centre, Montréal, QC, Canada.

Despite the success of antiretroviral therapy (ART), people living with HIV (PLWH) are still at higher risk for cardiovascular diseases (CVDs) that are mediated by chronic inflammation. Identification of novel inflammatory mediators with the inherent potential to be used as CVD biomarkers and also as therapeutic targets is critically needed for better risk stratification and disease management in PLWH. Here, we investigated the expression and potential role of the multi-isoform proinflammatory cytokine IL-32 in subclinical atherosclerosis in PLWH (n=49 with subclinical atherosclerosis and n=30 without) and HIV- controls (n=25 with subclinical atherosclerosis and n=24 without). While expression of all tested IL-32 isoforms (α, β, γ, D, ϵ, and θ) was significantly higher in peripheral blood from PLWH compared to HIV- controls, IL-32D and IL-32θ isoforms were further upregulated in HIV+ individuals with coronary artery atherosclerosis compared to their counterparts without. Upregulation of these two isoforms was associated with increased plasma levels of IL-18 and IL-1β and downregulation of the atheroprotective protein TRAIL, which together composed a unique atherosclerotic inflammatory signature specific for PLWH compared to HIV- controls. Logistic regression analysis demonstrated that modulation of these inflammatory variables was independent of age, smoking, and statin treatment. Furthermore, our functional data linked IL-32 to macrophage activation and production of IL-18 and downregulation of TRAIL, a mechanism previously shown to be associated with impaired cholesterol metabolism and atherosclerosis. Finally, increased expression of IL-32 isoforms in PLWH with subclinical atherosclerosis was associated with altered gut microbiome (increased pathogenic bacteria; and species) and lower abundance of the gut metabolite short-chain fatty acid (SCFA) caproic acid, measured in fecal samples from the study participants. Importantly, caproic acid diminished the production of IL-32, IL-18, and IL-1β in human PBMCs in response to bacterial LPS stimulation. In conclusion, our studies identified an HIV-specific atherosclerotic inflammatory signature including specific IL-32 isoforms, which is regulated by the SCFA caproic acid and that may lead to new potential therapies to prevent CVD in ART-treated PLWH.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fimmu.2021.664371DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8083984PMC
April 2021

HIV, HCV and risk of new-onset left ventricular dysfunction: the women's interagency HIV study.

AIDS 2021 Apr 15. Epub 2021 Apr 15.

Cardiology Section, San Francisco VA Health Care System and Department of Medicine, University of California San Francisco, San Francisco, CA 94121, USA Division of Cardiology, Department of Medicine, State University of New York Health Science Center - Brooklyn, Brooklyn, NY 11203, USA Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY 10461, USA Division of General Internal Medicine, Department of Medicine, Albert Einstein College of Medicine and Montefiore Health System, Bronx, NY 10461, USA Division of Cardiology, Department of Medicine, Albert Einstein College of Medicine and Montefiore Health System, Bronx, NY 10461, USA Section of Infectious Diseases, San Francisco VA Health Care System, and Departments of Medicine and Clinical Pharmacy, University of California San Francisco, San Francisco, CA 94121, USA Division of Cardiology, Department of Medicine, Johns Hopkins University, Baltimore, MD 21287, USA Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle WA 98109, USA Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA 94143, USA.

Background: HIV and HCV have each been linked with cardiac dysfunction. Studies of HIV have often lacked appropriate controls and primarily involved men, while data for HCV are sparse.

Methods: We performed repeat echocardiography over a median interval of 12 years in participants from the Women's Interagency HIV Study in order to evaluate the relationships of HIV and HCV with incident left ventricular (LV) dysfunction (systolic or diastolic).

Results: Of the 311 women included (age 39 ± 9), 70% were HIV and 20% HCV positive. Forty three participants (13.8%) developed LV dysfunction, of which 79.1% was diastolic. Compared to participants with neither infection, the group with HIV-HCV coinfection showed a significantly increased risk of incident LV dysfunction after adjustment for risk factors (RR = 2.96 [95% CI = 1.05-8.31]), but associations for the HCV monoinfected and HIV monoinfected groups were not statistically significant (RR = 2.54 [0.83-7.73] and RR = 1.66 [0.65-4.25], respectively). Comparison of HCV-positive and HCV-negative women showed a significantly increased risk independent of covariates (RR = 1.96 [1.02-3.77]), but this was not the case for HIV-positive vs. HIV-negative women (RR = 1.43 [0.76-2.69]). There was no evidence of HCV-by-HIV interaction. A more restrictive definition of LV diastolic dysfunction led to fewer incident cases, but a similar, though non-significant, risk estimate for HCV.

Conclusions: Among middle-aged women, HCV but not HIV infection was associated with a pronounced risk of incident LV dysfunction. Although the influence of residual confounding cannot be excluded, these findings bolster the potential benefits that could be realized by adopting recent recommendations for expanding HCV screening and treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/QAD.0000000000002920DOI Listing
April 2021

Brachial Flow-Mediated Dilation and Risk of Atrial Fibrillation in Older Adults: The Cardiovascular Health Study.

Vasc Health Risk Manag 2021 11;17:95-102. Epub 2021 Mar 11.

Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.

Background: Endothelial dysfunction is associated with common risk factors for AF and has been implicated in the pathophysiology of atrial fibrillation (AF) through a variety of mechanisms. We determined the prospective association of brachial flow-mediated dilation (FMD) with incident AF among older adults.

Methods: We included 2027 Cardiovascular Health Study participants (mean age=78.3 years, male=39%, Black=17%) who underwent brachial FMD measurement at the 1997 to 1998 clinic visit. Incident AF was ascertained by study electrocardiograms, hospital discharge diagnosis coding and Medicare claims data. Cox regression models were used to examine the association between FMD and incident AF.

Results: We identified 754 incident of AF cases (37%) over a median follow-up of 11.0 years. After adjusting for age, sex, race, height, weight, cardiovascular disease, cigarette smoking, hypertension, diabetes, kidney function, c-reactive protein, physical activity, alcohol consumption, and statins, the risk of AF did not differ according to brachial FMD response (4th vs 1st quartile hazard ratio (HR)=1.01, 95% confidence interval (CI): 0.81, 1.26; per FMD unit increment HR=1.01, 95% CI: 0.97, 1.05).

Conclusion: We found no relationship between brachial FMD and the risk of developing AF in this elderly cohort. Our findings suggest that the utility of brachial FMD as a risk marker for AF in older individuals is minimal.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/VHRM.S297720DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7961139PMC
March 2021

Associations of Serum Nonesterified Fatty Acids With Coronary Heart Disease Mortality and Nonfatal Myocardial Infarction: The CHS (Cardiovascular Health Study) Cohort.

J Am Heart Assoc 2021 Mar 8;10(6):e019135. Epub 2021 Mar 8.

Cardiovascular Nutrition Laboratory Jean Mayer USDA Human Nutrition Research Center on Aging Tufts University Boston MA.

Background Significant associations have been reported between serum total nonesterified fatty acid (NEFA) concentrations and coronary heart disease (CHD) mortality and incident nonfatal myocardial infarction (MI) in some prospective cohort studies. Little is known about whether individual or subclasses (saturated, polyunsaturated [n-6 and n-3], and fatty acids) of serum NEFAs relate to CHD mortality and nonfatal MI. Methods and Results CHS (Cardiovascular Health Study) participants (N=1681) who had no history of MI, angina, or revascularization or were free of MI at baseline (1996-1997) were included. NEFAs were quantified using gas chromatography. Cox regression analysis was used to evaluate associations of 5 subclasses and individual NEFAs with CHD composite (CHD mortality and nonfatal MI), CHD mortality, and incident nonfatal MI. During a median follow-up of 11.7 years, 266 cases of CHD death and 271 cases of nonfatal MI occurred. In the fully adjusted model, no significant associations were identified between individual NEFA and CHD composite. Exploratory analyses indicated that lauric acid (12:0) was negatively associated (hazard ratio [HR], 0.76; 95% CI, 0.59-0.98; =0.0328) and dihomo-γ-linolenic acid (20:3n-6) was positively associated with CHD mortality (HR, 1.34; 95% CI, 1.02-1.76; =0.0351). Elaidic acid (18:1n-7) was positively associated with incident nonfatal MI (HR, 1.46; 95% CI, 1.01-2.12; =0.0445). No significant associations were observed for NEFA subclass and any outcomes. Conclusions In CHS participants, 2 NEFAs, dihomo-γ-linolenic and elaidic acids, were positively associated with CHD mortality and nonfatal MI, respectively, suggesting potential susceptibility biomarkers for risks of CHD mortality and nonfatal MI.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/JAHA.120.019135DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8174223PMC
March 2021

Serum Individual Nonesterified Fatty Acids and Risk of Heart Failure in Older Adults.

Cardiology 2021;146(3):351-358. Epub 2021 Feb 25.

New York Academy of Medicine, New York, New York, USA.

Background: Heart failure (HF) is highly prevalent among older adults and is associated with high costs. Although serum total nonesterified fatty acids (NEFAs) have been positively associated with HF risk, the contribution of each individual NEFA to HF risk has not been examined.

Objective: The aim of this study was to examine the association of individual fasting NEFAs with HF risk in older adults.

Methods: In this prospective cohort study of older adults, we measured 35 individual NEFAs in 2,140 participants of the Cardiovascular Health Study using gas chromatography. HF was ascertained using review of medical records by an endpoint committee.

Results: The mean age was 77.7 ± 4.4 years, and 38.8% were male. During a median follow-up of 9.7 (maximum 19.0) years, 655 new cases of HF occurred. In a multivariable Cox regression model controlling for demographic and anthropometric variables, field center, education, serum albumin, glomerular filtration rate, physical activity, alcohol consumption, smoking, hormone replacement therapy, unintentional weight loss, and all other measured NEFAs, we observed inverse associations (HR [95% CI] per standard deviation) of nonesterified pentadecanoic (15:0) (0.73 [0.57-0.94]), γ-linolenic acid (GLA) (0.87 [0.75-1.00]), and docosahexaenoic acid (DHA) (0.73 [0.61-0.88]) acids with HF, and positive associations of nonesterified stearic (18:0) (1.30 [1.04-1.63]) and nervonic (24:1n-9) (1.17 [1.06-1.29]) acids with HF.

Conclusion: Our data are consistent with a higher risk of HF with nonesterified stearic and nervonic acids and a lower risk with nonesterified 15:0, GLA, and DHA in older adults. If confirmed in other studies, specific NEFAs may provide new targets for HF prevention.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000513917DOI Listing
February 2021

Nonesterified Fatty Acids and Kidney Function Decline in Older Adults: Findings From the Cardiovascular Health Study.

Am J Kidney Dis 2021 Feb 4. Epub 2021 Feb 4.

Division of General Medicine, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA.

Rationale & Objective: Circulating nonesterified fatty acids (NEFAs) make up a small portion of circulating lipids but are a metabolically important energy source. Excessive circulating NEFAs may contribute to lipotoxicity in many tissues, including the kidneys. We investigated the relationship between total circulating NEFA concentration and kidney outcomes in older, community-dwelling adults.

Study Design: Prospective cohort study.

Setting & Participants: 4,698 participants≥65 years of age in the Cardiovascular Health Study who underwent total fasting serum NEFA concentration measurements in 1992-1993.

Exposure: Fasting serum NEFA concentration at one time point.

Outcome: Three primary outcomes: estimated glomerular filtration rate (eGFR) decline of≥30%, the composite of eGFR decline≥30% or kidney failure with replacement therapy, and change in eGFR. These outcomes were assessed over 4- and 13-year periods.

Analytical Approach: Logistic regression for the dichotomous outcomes and mixed effects models for the continuous outcome, with sequential adjustment for baseline covariates. Inverse probability of attrition weighting was implemented to account for informative attrition during the follow-up periods.

Results: Serum NEFA concentrations were not independently associated with kidney outcomes. In unadjusted and partially adjusted analyses, the highest quartile of serum NEFA concentration (compared with lowest) was associated with a higher risk of≥30% eGFR decline at 4 years and faster rate of decline of eGFR. No associations were evident after adjustment for comorbidities, lipid levels, insulin sensitivity, medications, and vital signs: the odds ratio for the eGFR decline outcome was 1.33 (95% CI, 0.83-2.13), and the difference in eGFR slope in the highest versus lowest quartile of serum NEFA concentration was-0.15 (95% CI, -0.36 to 0.06) mL/min/1.73m per year.

Limitations: Single NEFA measurements, no measurements of post-glucose load NEFA concentrations or individual NEFA species, no measurement of baseline urine albumin.

Conclusions: A single fasting serum NEFA concentration was not independently associated with long-term adverse kidney outcomes in a cohort of older community-living adults.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1053/j.ajkd.2020.11.030DOI Listing
February 2021

Individual non-esterified fatty acids and incident atrial fibrillation late in life.

Heart 2021 Jan 22. Epub 2021 Jan 22.

Medical Service, San Francisco VA Medical Center, San Francisco, California, USA.

Objective: Obesity and dysmetabolism are major risk factors for atrial fibrillation (AF). Expansion of fat depots is associated with increased circulating total non-esterified fatty acids (NEFAs), elevated levels of which are associated with incident AF. We undertook comprehensive serum measurement of individual NEFA to identify specific associations with new-onset AF late in life.

Methods: The present study focused on participants with available serum and free of AF selected from the Cardiovascular Health Study, a community-based longitudinal investigation of older US adults. Thirty-five individual NEFAs were measured by gas chromatography. Cox regression was used to evaluate the association of individual NEFAs with incident AF.

Results: The study sample included 1872 participants (age 77.7±4.4). During median follow-up of 11.3 years, 715 cases of incident AF occurred. After concurrent adjustment of all NEFAs and full adjustment for potential confounders, higher serum concentration of nervonic acid (24:1 n-9), a long-chain monounsaturated fatty acid, was associated with higher risk of AF (HR per SD: 1.18, 95% CI 1.08 to 1.29; p<0.001). Conversely, higher serum concentration of gamma-linolenic acid (GLA) (18:3 n-6), a polyunsaturated n-6 fatty acid, was associated with lower risk of AF (HR per SD: 0.81, 95% CI 0.71 to 0.94; p=0.004). None of the remaining NEFAs was significantly associated with AF.

Conclusions: Among older adults, serum levels of non-esterified nervonic acid were positively associated, while serum levels of non-esterified GLA were inversely associated, with incident AF. If confirmed, these results could offer new strategies for AF prevention and early intervention in this segment of the population at highest risk.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/heartjnl-2020-317929DOI Listing
January 2021

Outcomes of ST-elevation myocardial infarction by age and sex in a low-income urban community: The Montefiore STEMI Registry.

Clin Cardiol 2020 Oct 28;43(10):1100-1109. Epub 2020 Jul 28.

Cardiology Section, San Francisco Veterans Affairs Health Care System, and Department of Medicine, University of California San Francisco, San Francisco, California, USA.

Objectives: To compare outcomes by age and sex in race/ethnic minorities presenting with ST-elevation myocardial infarction (STEMI), as studies are limited.

Methods: We studied sociodemographics, management, and outcomes in 1208 STEMI patients evaluated for primary percutaneous coronary intervention between 2008 and 2014 at Montefiore Health System (Bronx, NY). A majority of patients self-identified as nonwhite, and nearly two-thirds were young (<45 years) or middle-aged (45-64 years).

Results: Risk factors varied significantly across age groups; with more women and non-Hispanic whites, hypertension, diabetes, dyslipidemia, prior cardiovascular disease, non-sinus rhythm, and collagen vascular disease in the older age group (≥65 years); and higher body mass index, smoking, cocaine use, human immunodeficiency virus (HIV) infection and family history of heart disease in the young. Younger women had lower summary socioeconomic scores than younger men. Middle-aged women had more obesity and dysmetabolism, while men had more heavy alcohol use. There was greater disease severity with increasing age; with higher cardiac biomarkers, 3-vessel disease, cardiogenic shock, and coronary artery bypass grafting. Older patients had higher rates of death and death or readmission over 4.3 (interquartile range 2.4, 6.0) years of follow-up. Middle-aged women had higher rates of death or any readmission than men, but these differences were not significant after adjustment.

Conclusions: These findings indicate a high burden of risk factors in younger adults with STEMI from an inner-city community. Programs to target sociobehavioral factors in disadvantaged settings, including substance abuse, obesity, and risk of HIV, are necessary to more effectively address health disparities in STEMI and its adverse consequences.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/clc.23412DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7533997PMC
October 2020

Association of liver enzymes with incident diabetes in US Hispanic/Latino adults.

Diabet Med 2021 Jan 12:e14522. Epub 2021 Jan 12.

Albert Einstein College of Medicine, Bronx, NY, USA.

Introduction: Non-alcoholic fatty liver disease (NAFLD) has been associated with increased risk of incident diabetes. But such evidence is lacking in the Hispanic/Latino population, which has high prevalence of obesity and NAFLD.

Methods: We conducted a prospective cohort study of 6,928 adults of Hispanic/Latino background who had no diabetes, did not report excessive alcohol use, and no hepatitis B and C infection at baseline (2008-2011). We estimated risk ratios (RR) for incident diabetes, identified from visit 2 examination by glucose measurements or antidiabetic medication use, with baseline liver enzymes (alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyl transpeptidase (GGT)).

Results: A total of 738 adults developed diabetes during 6 years of follow-up. After adjusting for participant characteristics at baseline, versus the lowest quartile, highest quartiles of ALT and GGT were associated with risks for incident diabetes (RR for ALT: 1.51 [95% CI 1.03-2.22], p-trend = 0.006; RR for GGT: 2.39 [1.60-3.55], p-trend = 0.001). Higher GGT levels predicted increased risk of incident diabetes even among those with ALT or AST below the median levels. The associations of ALT and GGT with incident diabetes were similar among most Hispanic background but were not seen among Dominicans (p for interaction <0.05). The association of AST with incident diabetes was found only among light-to-moderate alcohol drinkers (RR = 1.50 [1.20-1.86]) but not abstainers (RR = 0.91 [0.69-1.20], p for interaction = 0.006).

Conclusion: Higher ALT and GGT levels are associated with increased risk of developing diabetes among Latinos. Liver enzyme tests might aid in diabetes prevention by identifying high-risk individuals.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/dme.14522DOI Listing
January 2021

Non-esterified fatty acids and telomere length in older adults: The Cardiovascular Health Study.

Metabol Open 2020 Dec 7;8:100058. Epub 2020 Sep 7.

Division of General Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.

Background: Telomeres shorten as organisms age, placing limits on cell proliferation and serving as a marker of biological aging. Non-esterified fatty acids (NEFAs) are a key mediator of age-related metabolic abnormalities. We aimed to determine if NEFAs are associated with telomere length in community-living older adults.

Material And Methods: We cross-sectionally studied 1648 participants of the Cardiovascular Health Study (CHS) who underwent concomitant telomere length measurement from a sample of 4715 participants who underwent measurement of circulating total fasting NEFAs in stored specimens from their 1992-3 clinic visit. We used linear regression and inverse probability weighting to model telomere length as a function of NEFAs with adjustment for age, gender, race, clinic, BMI, marital status, smoking status, alcohol intake, diabetes status, years of education, hypertension status, prevalent cardiovascular disease, C-reactive protein, total adiponectin, albumin, fetuin-A, fasting insulin, eGFR, total cholesterol, HDL-cholesterol, triglycerides, and general health status.

Results: Higher NEFAs were significantly associated with shorter telomere length, after adjusting for age, gender, race, and clinic site (β = -0.034; SE = 0.015;  = 0.02). Estimates remained similar in fully adjusted models where each SD of NEFA increment was associated with 0.042 kilobase (kb) pairs shorter telomere length (standard error = 0.016;  = 0.007); for comparison the coefficient for a single year of age in the same model was -0.017. These results were similar in strata of sex, and waist circumference although they tended to be strongest among participants in the youngest tertile of age (β = -0.079; SE = 0.029; P = 0.01).

Conclusions: In this population-based cohort of community-living elders, we observed a significant inverse association between NEFAs and telomere length. If confirmed, NEFAs may represent a promising target for interventions to slow biological aging.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.metop.2020.100058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7502331PMC
December 2020

Non-Esterified Fatty Acids and Risks of Frailty, Disability, and Mobility Limitation in Older Adults: The Cardiovascular Health Study.

J Am Geriatr Soc 2020 12 22;68(12):2890-2897. Epub 2020 Sep 22.

Division of General Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA.

Background/objectives: Non-esterified fatty acids (NEFAs) play central roles in the relationship between adiposity and glucose metabolism, and they have been implicated in the pathogenesis of cardiovascular disease, but few studies have assessed their effects on complex geriatric syndromes like frailty that cross multiple organ systems. We sought to determine the relationships between NEFAs and incident frailty, disability, and mobility limitation in a population-based cohort of older persons.

Methods: We analyzed 4,710 Cardiovascular Health Study (CHS) participants who underwent measurement of circulating total fasting NEFAs in 1992-1993 and were assessed for frailty in 1996-1997 and for disability and mobility limitation annually. We used ordinal logistic regression to model incident frailty, linear regression to model components of frailty, and Cox regression to model disability and mobility limitation in relation to baseline NEFAs. To ensure proportional hazards, we truncated follow-up at 9 years for disability and 6.5 years for mobility limitation.

Results: A total of 42 participants became frail and 510 became pre-frail over a 4-year period, and we documented 1,720 cases of disability and 1,225 cases of mobility limitation during follow-up. NEFAs were positively associated in a dose-dependent manner with higher risks of incident frailty, disability, and mobility limitation. The adjusted odds ratios for frailty were 1.37 (95% confidence interval [CI] = 1.01-1.86; P = .04) across extreme tertiles and 1.17 (95% CI = 1.03-1.33; P = .01) per standard deviation increment. The corresponding hazard ratios for incident disability were 1.14 (95% CI = 1.01-1.30; P = .04) and 1.11 (95% CI = 1.06-1.17; P < .0001); those for incident mobility limitation were 1.23 (95% CI = 1.06-1.43; P = .006) and 1.15 (95% CI = 1.08-1.22; P < .0001). Results were largely consistent among both men and women. Among individual components of frailty, NEFAs were significantly associated with self-reported exhaustion (β = .07; standard error = .03; P = .02).

Conclusion: Circulating NEFAs are significantly associated with frailty, disability, and mobility limitation among older adults. These results highlight the broad spectrum of adverse health issues associated with NEFA in older adults.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jgs.16793DOI Listing
December 2020

Association of human immunodeficiency virus and hepatitis C virus infection with long-term outcomes post-ST segment elevation myocardial infarction in a disadvantaged urban community.

Atherosclerosis 2020 10 27;311:60-66. Epub 2020 Aug 27.

University of California San Francisco and San Francisco Veterans Affairs Health Care System, 4150 Clement Street, San Francisco, CA, 94121, USA.

Background: HIV and HCV have been linked to an increased risk of cardiovascular disease (CVD). Their impact on long-term outcomes following ST-segment myocardial infarction (STEMI) has not been previously studied.

Methods: We leveraged data from a STEMI registry (n = 1208) at an inner-city health system to assess the influence of HIV and HCV on post-STEMI outcomes. Cox regression was used to compare HIV-monoinfected (n = 22), HCV-monoinfected (n = 26) and HIV-HCV-coinfected patients (n = 8) with the neither-infected group (n = 1152) with regard to death, death or any readmission, and death or CVD readmission.

Results: The cohort was majority black or Hispanic. Median follow-up was 4.3 years. Compared to the neither-infected group, the HIV-monoinfected group showed near-significantly higher risks of death or any readmission (HR = 1.62, 95% CI = 0.96, 2.74) and death or CVD readmission (HR = 1.82, 95% CI = 0.98, 3.39) after full adjustment. On similar comparison, the HCV-monoinfected group exhibited significantly higher risks of death (HR = 2.09, 95% CI = 1.05, 4.15) and death or any readmission (HR = 1.68, 95% CI = 1.07, 2.65), whereas the HIV-HCV-coinfected group showed higher risk of death (HR = 6.51, 95% CI = 2.28, 18.61).

Conclusions: In this cohort composed mostly of race-ethnic minorities, HIV monoinfection tended to be associated with 1.6-to-1.8-fold higher risk of death or readmission for any cause or CVD over long-term follow-up compared to neither infection, whereas HCV monoinfection was associated with 1.7-to-2.1-fold higher risk of death and death or any readmission, and HIV-HCV coinfection with 6.5-fold higher risk of death. These associations require further study in larger populations, but highlight the importance of identifying and treating HIV and HCV in patients presenting with STEMI.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.atherosclerosis.2020.08.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7572633PMC
October 2020

Relation of Biomarkers of Cardiac Injury, Stress, and Fibrosis With Cardiac Mechanics in Patients ≥ 65 Years of Age.

Am J Cardiol 2020 12 16;136:156-163. Epub 2020 Sep 16.

Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois.

High sensitivity cardiac troponin T (hscTnT), soluble ST2 (sST2), N-terminal B-type natriuretic peptide (NT-proBNP), and galectin-3 are biomarkers of cardiac injury, stress, myocardial stretch, and fibrosis. Elevated levels are associated with poor outcomes. However, their association with cardiac mechanics in older persons is unknown. Associations between these biomarkers and cardiac mechanics derived from speckle tracking echocardiography, including left ventricular longitudinal strain (LVLS), early diastolic strain, and left atrial reservoir strain (LARS) were evaluated using standardized beta coefficients () in a cross sectional analysis with cardiac biomarkers in older patients without cardiovascular disease, low ejection fraction, or wall motion abnormalities. Biomarker associations with strain were attenuated by demographics and risk factors. In adjusted models, LVLS was associated with continuous measures of hscTnT (β-0.06, p = 0.020), sST2 (β -0.05, p = 0.024) and NT-proBNP (β -0.06, p = 0.007). "High" levels (i.e., greater than prognostic cutpoint) of hscTnT (>13 ng/ml), sST2 (>35 ng/ml), and NT-proBNP (>190 pg/ml) were also associated with worse LVLS. In risk factor adjusted models, LARS was associated with hscTnT (β -0.08, p = 0.003) and NT-proBNP (β-0.18, p <0.0001). High hscTnT (>13 ng/ml) and high NT-proBNP (>190 pg/ml) were also both associated with worse LARS. Gal-3 was not associated with any strain measure. In conclusion, in persons ≥ 65 years of age, without cardiovascular disease, low ejection fraction, or wall motion abnormalities, hscTnT, sST2, and NT-proBNP are associated with worse LVLS. HscTnT and NT-proBNP are associated with worse LARS. In conclusion, these subclinical increases in blood biomarkers, and their associations with subtle diastolic and systolic dysfunction, may represent pre-clinical heart failure.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.amjcard.2020.09.013DOI Listing
December 2020

Sex-Specific Associations of Cardiovascular Risk Factors and Biomarkers With Incident Heart Failure.

J Am Coll Cardiol 2020 09;76(12):1455-1465

Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands. Electronic address:

Background: Whether cardiovascular (CV) disease risk factors and biomarkers associate differentially with heart failure (HF) risk in men and women is unclear.

Objectives: The purpose of this study was to evaluate sex-specific associations of CV risk factors and biomarkers with incident HF.

Methods: The analysis was performed using data from 4 community-based cohorts with 12.5 years of follow-up. Participants (recruited between 1989 and 2002) were free of HF at baseline. Biomarker measurements included natriuretic peptides, cardiac troponins, plasminogen activator inhibitor-1, D-dimer, fibrinogen, C-reactive protein, sST2, galectin-3, cystatin-C, and urinary albumin-to-creatinine ratio.

Results: Among 22,756 participants (mean age 60 ± 13 years, 53% women), HF occurred in 2,095 participants (47% women). Age, smoking, type 2 diabetes mellitus, hypertension, body mass index, atrial fibrillation, myocardial infarction, left ventricular hypertrophy, and left bundle branch block were strongly associated with HF in both sexes (p < 0.001), and the combined clinical model had good discrimination in men (C-statistic = 0.80) and in women (C-statistic = 0.83). The majority of biomarkers were strongly and similarly associated with HF in both sexes. The clinical model improved modestly after adding natriuretic peptides in men (ΔC-statistic = 0.006; likelihood ratio chi-square = 146; p < 0.001), and after adding cardiac troponins in women (ΔC-statistic = 0.003; likelihood ratio chi-square = 73; p < 0.001).

Conclusions: CV risk factors are strongly and similarly associated with incident HF in both sexes, highlighting the similar importance of risk factor control in reducing HF risk in the community. There are subtle sex-related differences in the predictive value of individual biomarkers, but the overall improvement in HF risk estimation when included in a clinical HF risk prediction model is limited in both sexes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jacc.2020.07.044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7493711PMC
September 2020

Genetic Studies of Leptin Concentrations Implicate Leptin in the Regulation of Early Adiposity.

Diabetes 2020 12 11;69(12):2806-2818. Epub 2020 Sep 11.

Department of Biostatistics, Boston University School of Public Health, Boston, MA.

Leptin influences food intake by informing the brain about the status of body fat stores. Rare mutations associated with congenital leptin deficiency cause severe early-onset obesity that can be mitigated by administering leptin. However, the role of genetic regulation of leptin in polygenic obesity remains poorly understood. We performed an exome-based analysis in up to 57,232 individuals of diverse ancestries to identify genetic variants that influence adiposity-adjusted leptin concentrations. We identify five novel variants, including four missense variants, in , , , and , and one intergenic variant near The missense variant Val94Met (rs17151919) in was common in individuals of African ancestry only, and its association with lower leptin concentrations was specific to this ancestry ( = 2 × 10, = 3,901). Using in vitro analyses, we show that the Met94 allele decreases leptin secretion. We also show that the Met94 allele is associated with higher BMI in young African-ancestry children but not in adults, suggesting that leptin regulates early adiposity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2337/db20-0070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7679778PMC
December 2020

Nonesterified Fatty Acids and Hospitalizations Among Older Adults: The Cardiovascular Health Study.

J Gerontol A Biol Sci Med Sci 2021 Jun;76(7):1326-1332

Division of General Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts.

Background: We sought to determine associations between total serum concentrations of nonesterified fatty acids (NEFAs) and incident total and cause-specific hospitalizations in a community-living cohort of older adults.

Methods: We included 4715 participants in the Cardiovascular Health Study who had fasting total serum NEFA measured at the 1992/1993 clinic visit and were followed for a median of 12 years. We identified all inpatient admissions requiring at least an overnight hospitalization and used primary diagnostic codes to categorize cause-specific hospitalizations. We used Cox proportional hazards regression models to determine associations with time-to-first hospitalization and Poisson regression for the rate ratios (RRs) of hospitalizations and days hospitalized.

Results: We identified 21 339 hospitalizations during follow-up. In fully adjusted models, higher total NEFAs were significantly associated with higher risk of incident hospitalization (hazard ratio [HR] per SD [0.2 mEq/L] = 1.07, 95% confidence interval [CI] = 1.03-1.10, p < .001), number of hospitalizations (RR per SD = 1.04, 95% CI = 1.01-1.07, p = .01), and total number of days hospitalized (RR per SD = 1.06, 95% CI = 1.01-1.10, p = .01). Among hospitalization subtypes, higher NEFA was associated with higher likelihood of mental, neurologic, respiratory, and musculoskeletal causes of hospitalization. Among specific causes of hospitalization, higher NEFA was associated with diabetes, pneumonia, and gastrointestinal hemorrhage.

Conclusions: Higher fasting total serum NEFAs are associated with a broad array of causes of hospitalization among older adults. While some of these were expected, our results illustrate a possible utility of NEFAs as biomarkers for risk of hospitalization, and total days hospitalized, in older adults. Further research is needed to determine whether interventions based on NEFAs might be feasible.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/gerona/glaa228DOI Listing
June 2021

Characterization of cardiac mechanics and incident atrial fibrillation in participants of the Cardiovascular Health Study.

JCI Insight 2020 10 2;5(19). Epub 2020 Oct 2.

Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.

Background: Left atrial (LA) and left ventricular (LV) remodeling are associated with atrial fibrillation (AF). The prospective associations of impairment in cardiac mechanical function, as assessed by speckle-tracking echocardiography, with incident AF are less clear.

Methods: In the Cardiovascular Health Study, a community-based cohort of older adults, participants free of AF with echocardiograms of adequate quality for speckle tracking were included. We evaluated the associations of indices of cardiac mechanics (LA reservoir strain, LV longitudinal strain, and LV early diastolic strain rate) with incident AF.

Results: Of 4341 participants with strain imaging, participants with lower LA reservoir strain were older, had more cardiometabolic risk factors, and had lower renal function at baseline. Over a median follow-up of 10 years, 497 (11.4%) participants developed AF. Compared with the highest quartile of LA reservoir strain, the lowest quartile of LA reservoir strain was associated with higher risk of AF after covariate adjustment, including LA volume and LV longitudinal strain (heart rate [HR], 1.80; 95% CI, 1.31-2.45; P < 0.001). The association of LA reservoir strain and AF was stronger in subgroups with higher blood pressure, NT-proBNP, and LA volumes. There were no associations of LV longitudinal strain and LV early diastolic strain rate with incident AF after adjustment for LA reservoir strain.

Conclusion: Lower LA reservoir strain was associated with incident AF, independent of LV mechanics, and with stronger associations in high-risk subgroups. These findings suggest that LA mechanical dysfunction precedes the development of AF. Therapies targeting LA mechanical dysfunction may prevent progression to AF.

Funding: This research was supported by contracts HHSN268201200036C, HHSN268200800007C, HHSN268201800001C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, and N01HC85086 and grants KL2TR001424, R01HL107577, U01HL080295, and U01HL130114 from the NIH's National Center for Advancing Translational Sciences, and National Heart, Lung, and Blood Institute (NHLBI), with additional contribution from the National Institute of Neurological Disorders and Stroke (NINDS). Additional support was provided by R01AG023629 from the National Institute on Aging (NIA). A full list of principal CHS investigators and institutions can be found at CHS-NHLBI.org.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1172/jci.insight.141656DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7566702PMC
October 2020

Underuse of Cardiovascular Medications in Individuals With Known Lower Extremity Peripheral Artery Disease: HCHS/SOL.

J Am Heart Assoc 2020 08 5;9(16):e015451. Epub 2020 Aug 5.

Department of Epidemiology and Population Health Albert Einstein College of Medicine Bronx NY.

Background Underuse of cardiovascular medications for secondary prevention among individuals with peripheral artery disease (PAD) has been reported. Little is known about PAD treatment status in the Hispanic/Latino population in the United States, who may have limited access to health care and who have worse clinical outcomes than non-Hispanic individuals. Methods and Results We studied the use of cardiovascular therapies in 1244 Hispanic/Latino individuals recruited from 4 sites in the United States, including 826 individuals who reported diagnosis of PAD by physician and 418 individuals with coronary artery disease alone, in the Hispanic Community Health Study/Study of Latinos. We compared the prevalence of using antiplatelet therapy, lipid-lowering therapy and antihypertensive therapy by PAD and coronary artery disease status. Among those with PAD, we studied factors associated with taking cardiovascular medications, including demographic and socioeconomic factors, acculturation, access to health care and comorbidities, using multivariable regression models. The overall prevalence for individuals with PAD taking antiplatelet therapy, lipid-lowering therapy and, among hypertensive individuals, antihypertensive therapy was 31%, 26% and 57%, respectively. Individuals of Mexican background had the lowest use for all classes of cardiovascular medications. Older age, number of doctor visits and existing hypertension and diabetes mellitus were significantly associated with taking cardiovascular therapies in adjusted models. Compared with those with PAD alone, individuals with PAD and concurrent coronary artery disease were 1.52 (95% CI, 1.20-1.93) and 1.74 (1.30-2.32) times more likely to use antiplatelet agents and statins according to multivariable analysis. No significant difference of antihypertensive medication use was found among PAD patients with or without coronary artery disease. Conclusions Hispanic/Latino individuals with known PAD underuse cardiovascular medications recommended in clinical guidelines. More efforts should be directed to improve treatment in this important group.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/JAHA.119.015451DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7660818PMC
August 2020

Computable Phenotype Implementation for a National, Multicenter Pragmatic Clinical Trial: Lessons Learned From ADAPTABLE.

Circ Cardiovasc Qual Outcomes 2020 06 29;13(6):e006292. Epub 2020 May 29.

Department of Population Health Sciences, Weill Cornell Medicine, New York Presbyterian-Weill Cornell Campus, New York (M.G.W.).

Background: Many large-scale cardiovascular clinical trials are plagued with escalating costs and low enrollment. Implementing a computable phenotype, which is a set of executable algorithms, to identify a group of clinical characteristics derivable from electronic health records or administrative claims records, is essential to successful recruitment in large-scale pragmatic clinical trials. This methods paper provides an overview of the development and implementation of a computable phenotype in ADAPTABLE (Aspirin Dosing: a Patient-Centric Trial Assessing Benefits and Long-Term Effectiveness)-a pragmatic, randomized, open-label clinical trial testing the optimal dose of aspirin for secondary prevention of atherosclerotic cardiovascular disease events.

Methods And Results: A multidisciplinary team developed and tested the computable phenotype to identify adults ≥18 years of age with a history of atherosclerotic cardiovascular disease without safety concerns around using aspirin and meeting trial eligibility criteria. Using the computable phenotype, investigators identified over 650 000 potentially eligible patients from the 40 participating sites from Patient-Centered Outcomes Research Network-a network of Clinical Data Research Networks, Patient-Powered Research Networks, and Health Plan Research Networks. Leveraging diverse recruitment methods, sites enrolled 15 076 participants from April 2016 to June 2019. During the process of developing and implementing the ADAPTABLE computable phenotype, several key lessons were learned. The accuracy and utility of a computable phenotype are dependent on the quality of the source data, which can be variable even with a common data model. Local validation and modification were required based on site factors, such as recruitment strategies, data quality, and local coding patterns. Sustained collaboration among a diverse team of researchers is needed during computable phenotype development and implementation.

Conclusions: The ADAPTABLE computable phenotype served as an efficient method to recruit patients in a multisite pragmatic clinical trial. This process of development and implementation will be informative for future large-scale, pragmatic clinical trials. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02697916.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/CIRCOUTCOMES.119.006292DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7321832PMC
June 2020

Practice advisory update summary: Patent foramen ovale and secondary stroke prevention: Report of the Guideline Subcommittee of the American Academy of Neurology.

Neurology 2020 05 29;94(20):876-885. Epub 2020 Apr 29.

From the Department of Neurology (S.R.M., S.E.K.), University of Pennsylvania School of Medicine, Philadelphia; Department of Neurology (G.S.G., L.R.), University of Kansas Medical Center, MO; Institute for Clinical Research and Health Policy Studies (D.M.K.), Tufts University School of Medicine, Boston, MA; Cardiology Section (J.R.K.), San Francisco Veterans Affairs Health Care System, and Departments of Medicine, and Epidemiology and Biostatistics (J.R.K.), University of California San Francisco; Division of Cardiology (S.H.), Columbia University Medical Center, New York; Department of Medicine (Cardiology) (J.D.C.), University of Colorado School of Medicine, Aurora; Department of Neurology (K.I.), New York University; and Department of Neurology (N.S.), Kaiser Permanente, Los Angeles, CA.

Objective: To update the 2016 American Academy of Neurology (AAN) practice advisory for patients with stroke and patent foramen ovale (PFO).

Methods: The guideline panel followed the AAN 2017 guideline development process to systematically review studies published through December 2017 and formulate recommendations.

Major Recommendations: In patients being considered for PFO closure, clinicians should ensure that an appropriately thorough evaluation has been performed to rule out alternative mechanisms of stroke (level B). In patients with a higher risk alternative mechanism of stroke identified, clinicians should not routinely recommend PFO closure (level B). Clinicians should counsel patients that having a PFO is common; that it occurs in about 1 in 4 adults in the general population; that it is difficult to determine with certainty whether their PFO caused their stroke; and that PFO closure probably reduces recurrent stroke risk in select patients (level B). In patients younger than 60 years with a PFO and embolic-appearing infarct and no other mechanism of stroke identified, clinicians may recommend closure following a discussion of potential benefits (absolute recurrent stroke risk reduction of 3.4% at 5 years) and risks (periprocedural complication rate of 3.9% and increased absolute rate of non-periprocedural atrial fibrillation of 0.33% per year) (level C). In patients who opt to receive medical therapy alone without PFO closure, clinicians may recommend an antiplatelet medication such as aspirin or anticoagulation (level C).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1212/WNL.0000000000009443DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7526671PMC
May 2020

Fatty Acid Binding Protein-4 and Risk of Cardiovascular Disease: The Cardiovascular Health Study.

J Am Heart Assoc 2020 04 6;9(7):e014070. Epub 2020 Apr 6.

Division of General Medicine Beth Israel Deaconess Medical Center Boston MA.

Background FABP-4 (fatty acid binding protein-4) is a lipid chaperone in adipocytes and has been associated with prognosis in selected clinical populations. We investigated the associations between circulating FABP-4, risk of incident cardiovascular disease (CVD), and risk of CVD mortality among older adults with and without established CVD. Methods and Results In the Cardiovascular Health Study, we measured FABP4 levels in stored specimens from the 1992-993 visit and followed participants for incident CVD if they were free of prevalent CVD at baseline and for CVD mortality through June 2015. We used Cox regression to estimate hazard ratios for incident CVD and CVD mortality per doubling in serum FABP-4 adjusted for age, sex, race, field center, waist circumference, blood pressure, lipids, fasting glucose, and C-reactive protein. Among 4026 participants free of CVD and 681 with prevalent CVD, we documented 1878 cases of incident CVD and 331 CVD deaths, respectively. In adjusted analyses, FABP-4 was modestly associated with risk of incident CVD (mean, 34.24; SD, 18.90; HR, 1.10 per doubling in FABP-4, 95% CI, 1.00-1.21). In contrast, FABP-4 was more clearly associated with risk of CVD mortality among participants without (HR hazard ratio 1.24, 95% CI, 1.10-1.40) or with prevalent CVD (HR hazard ratio 1.57, 95% CI, 1.24-1.98). These associations were not significantly modified by sex, age, and waist circumference. Conclusions Serum FABP-4 is modestly associated with risk of incident CVD even after adjustment for standard risk factors, but more strongly associated with CVD mortality among older adults with and without established CVD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/JAHA.119.014070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7428637PMC
April 2020

Soluble CD14 and Risk of Heart Failure and Its Subtypes in Older Adults.

J Card Fail 2020 May 9;26(5):410-419. Epub 2020 Mar 9.

Cardiology Section, San Francisco Veterans Affairs Health Care System, and Department of Medicine, University of California San Francisco, San Francisco, California; Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California. Electronic address:

Background: CD14 is a membrane glycoprotein primarily expressed by myeloid cells that plays a key role in inflammation. Soluble CD14 (sCD14) levels carry a poor prognosis in chronic heart failure (HF), but whether elevations in sCD14 precede HF is unknown. We tested the hypothesis that sCD14 is associated with HF incidence and its subtypes independent of major inflammatory biomarkers among older adults.

Methods And Results: We included participants in the Cardiovascular Health Study without preexisting HF and available baseline sCD14. We evaluated the associations of sCD14, high-sensitivity C-reactive protein (hsCRP), interleukin (IL)-6, and white blood cell count (WBC) with incident HF and subtypes using Cox regression. Among 5217 participants, 1878 had incident HF over 13.6 years (609 classifiable as HF with preserved ejection fraction [HFpEF] and 419 as HF with reduced ejection fraction [HFrEF]). After adjusting for clinical and laboratory covariates, sCD14 was significantly associated with incident HF (hazard ratio [HR]: 1.56 per doubling, 95% confidence interval [CI]: 1.29-1.89), an association that was numerically stronger than for hsCRP (HR per doubling: 1.10, 95% CI: 1.06-1.15), IL-6 (HR: 1.18, 95% CI: 1.10-1.25), and WBC (HR: 1.24, 95% CI: 1.09-1.42), and that remained significant after adjustment for the other markers of inflammation. This association for sCD14 was observed with HFpEF (HR: 1.50, 95% CI: 1.07-2.10) but not HFrEF (HR: 0.99, 95% CI: 0.67-1.49).

Conclusions: Plasma sCD14 was associated with incident HF independently and numerically more strongly than other major inflammatory markers. This association was only observed with HFpEF in the subset with classifiable HF subtypes. Pending replication, these findings have potentially important therapeutic implications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cardfail.2020.03.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7245550PMC
May 2020

Metabolomic Profiling of Left Ventricular Diastolic Dysfunction in Women With or at Risk for HIV Infection: The Women's Interagency HIV Study.

J Am Heart Assoc 2020 02 17;9(4):e013522. Epub 2020 Feb 17.

Department of Epidemiology & Population Health Albert Einstein College of Medicine Bronx NY.

Background People living with HIV have an increased risk of left ventricular diastolic dysfunction (LVDD) and heart failure. HIV-associated LVDD may reflect both cardiomyocyte and systemic metabolic derangements, but the underlying pathways remain unclear. Methods and Results To explore such pathways, we conducted a pilot study in the Bronx and Brooklyn sites of the WIHS (Women's Interagency HIV Study) who participated in concurrent, but separate, metabolomics and echocardiographic ancillary studies. Liquid chromatography tandem mass spectrometry-based metabolomic profiling was performed on plasma samples from 125 HIV-infected (43 with LVDD) and 35 HIV-uninfected women (9 with LVDD). Partial least squares discriminant analysis identified polar metabolites and lipids in the glycerophospholipid-metabolism and fatty-acid-oxidation pathways associated with LVDD. After multivariable adjustment, LVDD was significantly associated with higher concentrations of diacylglycerol 30:0 (odds ratio [OR], 1.60, 95% CI [1.01-2.55]); triacylglycerols 46:0 (OR 1.60 [1.04-2.48]), 48:0 (OR 1.63 [1.04-2.54]), 48:1 (OR 1.62 [1.01-2.60]), and 50:0 (OR 1.61 [1.02-2.53]); acylcarnitine C7 (OR 1.88 [1.21-2.92]), C9 (OR 1.99 [1.27-3.13]), and C16 (OR 1.80 [1.13-2.87]); as well as lower concentrations of phosphocholine (OR 0.59 [0.38-0.91]). There was no evidence of effect modification of these relationships by HIV status. Conclusions In this pilot study, women with or at risk of HIV with LVDD showed alterations in plasma metabolites in the glycerophospholipid-metabolism and fatty-acid-oxidation pathways. Although these findings require replication, they suggest that improved understanding of metabolic perturbations and their potential modification could offer new approaches to prevent cardiac dysfunction in this high-risk group.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/JAHA.119.013522DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7070185PMC
February 2020

Sleep-disordered breathing and left ventricular scar on cardiac magnetic resonance: results of the Multi-Ethnic Study of Atherosclerosis.

J Clin Sleep Med 2020 06;16(6):855-862

Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, Massachusetts.

Study Objectives: The objectives of this study were to evaluate the independent association between sleep-disordered breathing (SDB) using overnight polysomnography and left ventricular (LV) scar using cardiac magnetic resonance (CMR) with late-gadolinium enhancement in a community-based cohort of the Multi-Ethnic Study of Atherosclerosis.

Methods: Our analytical sample includes 934 participants from the fifth examination of the Multiethnic Study of Atherosclerosis who underwent both polysomnography and CMR. SDB was categorized as follows: no-SDB (apnea-hypopnea index [AHI] < 5 events/h), mild SDB (5 events/h ≤ AHI < 15 events/h), and moderate-severe SDB (AHI ≥ 15 events/h). LV scar was considered present if there was presence of scar on CMR (late-gadolinium enhancement > 0%). Logistic regression with multivariable adjustment for confounders (age, sex, race/ethnicity, body mass index, and cardiometabolic risk factors) was used to examine the independent association of SDB with LV scar. Confounders were identified using directed acyclic graphs.

Results: The mean age of our sample was 67.0 ± 8.5 years (SD), with 49% (n = 461) females and a prevalence of SDB (AHI ≥ 5 events/h) of 63% (n = 590). LV scar was more prevalent in individuals with SDB (9.5%) versus those without SDB (3.8%; P < .01), and 88% of all LV scars were clinically unrecognized. After multivariable adjustment, both mild SDB and moderate-severe SDB were independently associated with LV scar (odds ratio, 2.53; 95% confidence interval, 1.13-5.64 and odds ratio, 2.31; 95% confidence interval, 1.01-5.24, respectively).

Conclusions: In a community-based cohort, SDB (including mild) is independently associated with a more than 2-fold increase in the odds of LV scar presence measured using CMR with late-gadolinium enhancement. Most LV scars were clinically unrecognized. The impact of SDB treatment on subclinical myocardial infarction needs to be investigated in future studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5664/jcsm.8340DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7849673PMC
June 2020

Hyperglycaemia, adverse outcomes and impact of intravenous insulin therapy in patients presenting with acute ST-elevation myocardial infarction in a socioeconomically disadvantaged urban setting: The Montefiore STEMI Registry.

Endocrinol Diabetes Metab 2020 Jan 14;3(1):e00089. Epub 2019 Aug 14.

San Francisco Veterans Affairs Health Care System and University of California San Francisco San Francisco CA USA.

Background: Hyperglycaemia occurs frequently in ST-elevation myocardial infarction (STEMI) and is associated with poor outcomes, for which continuous insulin infusion therapy (CIIT) may be beneficial. Information is limited regarding hyperglycaemia in acute STEMI affecting urban minority populations, or how CIIT fares in such real-world settings.

Methods And Results: We assembled an acute STEMI registry at an inner-city health system, focusing on patients with initial blood glucose ≥180 mg/dL to determine the impact of CIIT vs usual care. Clinical and outcomes data were added through linkage to electronic records. Inverse-probability-of-treatment weighting using propensity scores (PS) was used to compare CIIT vs no CIIT. The 1067 patients included were mostly Hispanic or African American; 356 had blood glucose ≥180 mg/dL. Such pronounced hyperglycaemia was related to female sex, minority race-ethnicity and lower socioeconomic score, and associated with increased death and death or CVD readmission. CIIT was preferentially used in patients with marked hyperglycaemia and was associated with in-hospital hypoglycaemia (21% vs 11%,  = .019) and, after PS weighting, with increased in-hospital (RR 3.23, 95% CI 0.94, 11.06) and 1-year (RR 2.26, 95% CI 1.02, 4.98) mortality. No significant differences were observed for death at 30 days or throughout follow-up, or death and readmission at any time point.

Conclusions: Pronounced hyperglycaemia was common and associated with adverse prognosis in this urban population. CIIT met with selective use and was associated with hypoglycaemia, together with increased mortality at specific time points. Given the burden of metabolic disease, particularly among race-ethnic minorities, assessing the benefits of CIIT is a prerogative that requires evaluation in large-scale randomized trials.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/edm2.89DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6947698PMC
January 2020

Association of acculturation with cardiac structure and function among Hispanics/Latinos: a cross-sectional analysis of the echocardiographic study of Latinos.

BMJ Open 2019 11 28;9(11):e028729. Epub 2019 Nov 28.

Department of Medicine/Cardiology, Yeshiva University Albert Einstein College of Medicine, Bronx, New York, USA.

Objective: Hispanics/Latinos, the largest immigrant population in the USA, undergo the process of acculturation and have a large burden of heart failure risk. Few studies have examined the association of acculturation on cardiac structure and function.

Design: Cross-sectional.

Setting: The Echocardiographic Study of Latinos.

Participants: 1818 Hispanic adult participants with baseline echocardiographic assessment and acculturation measured by the Short Acculturation Scale, nativity, age at immigration, length of US residence, generational status and language.

Primary And Secondary Outcome Measures: Echocardiographic assessment of left atrial volume index (LAVI), left ventricular mass index (LVMI), early diastolic transmitral inflow and mitral annular velocities.

Results: The study population was predominantly Spanish-speaking and foreign-born with mean residence in the US of 22.7 years, mean age of 56.4 years; 50% had hypertension, 28% had diabetes and 44% had a body mass index >30 kg/m. Multivariable analyses demonstrated higher LAVI with increasing years of US residence. Foreign-born and first-generation participants had higher E/e' but lower LAVI and e' velocities compared with the second generation. Higher acculturation and income >$20K were associated with higher LVMI, LAVI and E/e' but lower e' velocities. Preferential Spanish-speakers with an income <$20K had a higher E/e'.

Conclusions: Acculturation was associated with abnormal cardiac structure and function, with some effect modification by socioeconomic status.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bmjopen-2018-028729DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6924788PMC
November 2019

Sex- and Poverty-Specific Patterns in Cardiovascular Disease Mortality Associated With Human Immunodeficiency Virus, New York City, 2007-2017.

Clin Infect Dis 2020 07;71(3):491-498

Bureau of Human Immunodeficiency Virus Prevention and Control, New York City Department of Health and Mental Hygiene, New York, USA.

Background: Human immunodeficiency virus (HIV) may affect the risk of death due to cardiovascular disease (CVD) differently in men versus women.

Methods: We examined CVD mortality rates between 2007 and 2017 among all New York City residents living with HIV and aged 13+ by sex, using data from city HIV surveillance and vital statistics and the National Death Index. Residents without HIV were enumerated using modified US intercensal estimates. We determined associations of HIV status with CVD mortality by sex and neighborhood poverty, defined as the percent of residents living below the federal poverty level, after accounting for age, race/ethnicity, and year.

Results: There were 3234 CVD deaths reported among 147 915 New Yorkers living with HIV, with the proportion of deaths due to CVD increasing from 11% in 2007 to 22% in 2017. The age-standardized CVD mortality rate was 2.7/1000 person-years among both men and women with HIV. The relative rate of CVD mortality associated with HIV status was significantly higher among women (adjusted rate ratio [aRR] 1.7, 95% confidence interval [CI] 1.6-1.8) than men (aRR 1.2, 95% CI 1.1-1.3) overall, and within strata defined by neighborhood poverty. Sex differences in CVD mortality rates were the greatest when comparing individuals living with HIV and having detectable HIV RNA and CD4+ T-cell counts <500 cells/uL with individuals living without HIV.

Conclusions: Among people with HIV, 1 in 5 deaths is now associated with CVD. HIV providers should recognize the CVD risk among women with HIV, and reinforce preventive measures (eg, smoking cessation, blood pressure control, lipid management) and viremic control among people living with HIV regardless of neighborhood poverty to reduce CVD mortality.Human immunodeficiency virus (HIV) increases cardiovascular disease mortality risks to a greater degree among women than men, even after accounting for neighborhood poverty. HIV providers should emphasize cardiovascular disease prevention (eg, smoking cessation, hypertension control, lipid management) and viremic control.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/cid/ciz852DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7384322PMC
July 2020