Addition of 24‐hour heart rate variability parameters to the Cardiovascular Health Study stroke risk score and prediction of incident stroke: The Cardiovascular Health Study

Background Heart rate variability (HRV) characterizes cardiac autonomic functioning. The association of HRV with stroke is uncertain. We examined whether 24‐hour HRV added predictive value to the Cardiovascular Health Study clinical stroke risk score (CHS‐SCORE), previously developed at the baseline examination. Methods and Results N=884 stroke‐free CHS participants (age 75.3±4.6), with 24‐hour Holters adequate for HRV analysis at the 1994–1995 examination, had 68 strokes over ≤8 year follow‐up (median 7.3 [interquartile range 7.1–7.6] years). The value of adding HRV to the CHS‐SCORE was assessed with stepwise Cox regression analysis. The CHS‐SCORE predicted incident stroke (HR=1.06 per unit increment, P=0.005). Two HRV parameters, decreased coefficient of variance of NN intervals (CV%, P=0.031) and decreased power law slope (SLOPE, P=0.033) also entered the model, but these did not significantly improve the c‐statistic (P=0.47). In a secondary analysis, dichotomization of CV% (LOWCV% ≤12.8%) was found to maximally stratify higher‐risk participants after adjustment for CHS‐SCORE. Similarly, dichotomizing SLOPE (LOWSLOPE <−1.4) maximally stratified higher‐risk participants. When these HRV categories were combined (eg, HIGHCV% with HIGHSLOPE), the c‐statistic for the model with the CHS‐SCORE and combined HRV categories was 0.68, significantly higher than 0.61 for the CHS‐SCORE alone (P=0.02). Conclusions In this sample of older adults, 2 HRV parameters, CV% and power law slope, emerged as significantly associated with incident stroke when added to a validated clinical risk score. After each parameter was dichotomized based on its optimal cut point in this sample, their composite significantly improved prediction of incident stroke during ≤8‐year follow‐up. These findings will require validation in separate, larger cohorts. Keywords: autonomic nervous system, clinical stroke risk model, heart rate variability, prediction, predictors, risk prediction, risk stratification, strok

Adipokines and the Right Ventricle: The MESA-RV Study.

ObjectiveObesity is associated with changes in both right (RV) and left (LV) ventricular morphology, but the biological basis of this finding is not well established. We examined whether adipokine levels were associated with RV morphology and function in a population-based multiethnic sample free of clinical cardiovascular disease.MethodsWe examined relationships of leptin, resistin, TNF-α, and adiponectin with RV morphology and function (from cardiac MRI) in participants (n = 1,267) free of clinical cardiovascular disease from the Multi-Ethnic Study of Atherosclerosis (MESA)-RV study. Multivariable regressions (linear, quantile [25th and 75th] and generalized additive models [GAM]) were used to examine the independent association of each adipokine with RV mass, RV end-diastolic volume (RVEDV), RV end-systolic volume (RVESV), RV stroke volume (RVSV) and RV ejection fraction (RVEF).ResultsHigher leptin levels were associated with significantly lower levels of RV mass, RVEDV, RVESV and stroke volume, but not RVEF, after adjustment for age, gender, race, height and weight. These associations were somewhat attenuated but still significant after adjustment for traditional risk factors and covariates, and were completely attenuated when correcting for the respective LV measures. There were no significant interactions of age, gender, or race/ethnicity on the relationship between the four adipokines and RV structure or function.ConclusionsLeptin levels are associated with favorable RV morphology in a multi-ethnic population free of cardiovascular disease, however these associations may be explained by a yet to be understood bi-ventricular process as this association was no longer present after adjustment for LV values. These findings complement the associations previously shown between adipokines and LV structure and function in both healthy and diseased patients. The mechanisms linking adipokines to healthy cardiovascular function require further investigation

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

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 &gt;30 kg/m2. 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 &gt;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

Bone mineral density and risk of heart failure in older adults: The Cardiovascular Health Study

Background Despite increasing evidence of a common link between bone and heart health, the relationship between bone mineral density ( BMD ) and heart failure ( HF ) risk remains insufficiently studied. Methods and Results We investigated whether BMD measured by dual‐energy x‐ray absorptiometry was associated with incident HF in an older cohort. Cox models were stratified by sex and interactions of BMD with race assessed. BMD was examined at the total hip and femoral neck separately, both continuously and by World Health Organization categories. Of 1250 participants, 442 (55% women) developed HF during the median follow‐up of 10.5 years. In both black and nonblack women, neither total hip nor femoral neck BMD was significantly associated with HF ; there was no significant interaction by race. In black and nonblack men, total hip, but not femoral neck, BMD was significantly associated with HF , with evidence of an interaction by race. In nonblack men, lower total hip BMD was associated with higher HF risk (hazard ratio, 1.13 [95% CI, 1.01–1.26] per 0.1 g/cm 2 decrement), whereas in black men, lower total hip BMD was associated with lower HF risk (hazard ratio, 0.74 [95% CI, 0.59–0.94]). There were no black men with total hip osteoporosis. Among nonblack men, total hip osteoporosis was associated with higher HF risk (hazard ratio, 2.83 [95% CI, 1.39–5.74]) compared with normal BMD . Conclusions Among older adults, lower total hip BMD was associated with higher HF risk in nonblack men but lower risk in black men, with no evidence of an association in women. Further research is needed to replicate these findings and to study potential underlying pathways. </jats:sec

Association of alcohol consumption after development of heart failure with survival among older adults in the Cardiovascular Health Study

Importance: More than 1 million older adults develop heart failure annually. The association of alcohol consumption with survival among these individuals after diagnosis is unknown. Objective: To determine whether alcohol use is associated with increased survival among older adults with incident heart failure. Design, Setting, and Participants: This prospective cohort study included 5888 community-dwelling adults aged 65 years or older who were recruited to participate in the Cardiovascular Health Study between June 12, 1989, and June 1993, from 4 US sites. Of the total participants, 393 individuals had a new diagnosis of heart failure within the first 9 years of follow-up through June 2013. The study analysis was performed between January 19, 2016, and September 22, 2016. Exposures: Alcohol consumption was divided into 4 categories: abstainers (never drinkers), former drinkers, 7 or fewer alcoholic drinks per week, and more than 7 drinks per week. Primary Outcomes and Measures: Participant survival after the diagnosis of incident heart failure. Results: Among the 393 adults diagnosed with incident heart failure, 213 (54.2%) were female, 339 (86.3%) were white, and the mean (SD) age was 78.7 (6.0) years. Alcohol consumption after diagnosis was reported in 129 (32.8%) of the participants. Across alcohol consumption categories of long-term abstainers, former drinkers, consumers of 1-7 drinks weekly and consumers of more than 7 drinks weekly, the percentage of men (32.1%, 49.0%, 58.0%, and 82.4%, respectively; P \u3c .001 for trend), white individuals (78.0%, 92.7%, 92.0%, and 94.1%, respectively, P \u3c. 001 for trend), and high-income participants (22.0%, 43.8%, 47.3%, and 64.7%, respectively; P \u3c .001 for trend) increased with increasing alcohol consumption. Across the 4 categories, participants who consumed more alcohol had more years of education (mean, 12 years [interquartile range (IQR), 8.0-10.0 years], 12 years [IQR, 11.0-14.0 years], 13 years [IQR, 12.0-15.0 years], and 13 years [IQR, 12.0-14.0 years]; P \u3c .001 for trend). Diabetes was less common across the alcohol consumption categories (32.1%, 26.0%, 22.3%, and 5.9%, respectively; P = .01 for trend). Across alcohol consumption categories, there were fewer never smokers (58.3%, 44.8%, 35.7%, and 29.4%, respectively; P \u3c .001 for trend) and more former smokers (34.5%, 38.5%, 50.0%, and 52.9%, respectively; P = .006 for trend). After controlling for other factors, consumption of 7 or fewer alcoholic drinks per week was associated with additional mean survival of 383 days (95% CI, 17-748 days; P = .04) compared with abstinence from alcohol. Although the robustness was limited by the small number of individuals who consumed more than 7 drinks per week, a significant inverted U-shaped association between alcohol consumption and survival was observed. Multivariable model estimates of mean time from heart failure diagnosis to death were 2640 days (95% CI, 1967-3313 days) for never drinkers, 3046 days (95% CI, 2372-3719 days) for consumers of 0 to 7 drinks per week, and 2806 (95% CI, 1879-3734 days) for consumers of more than 7 drinks per week (P = .02). Consumption of 10 drinks per week was associated with the longest survival, a mean of 3381 days (95% CI, 2806-3956 days) after heart failure diagnosis. Conclusions and Relevance: These findings suggest that limited alcohol consumption among older adults with incident heart failure is associated with survival benefit compared with long-term abstinence. These findings suggest that older adults who develop heart failure may not need to abstain from moderate levels of alcohol consumption

The effect of baseline physical activity on cardiovascular outcomes and new-onset diabetes in patients treated for hypertension and left ventricular hypertrophy: the LIFE study

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74584/1/j.1365-2796.2007.01808.x.pd

Genetically Elevated Fetuin-A Levels, Fasting Glucose Levels, and Risk of Type 2 Diabetes: The Cardiovascular Health Study*

OBJECTIVE Fetuin-A levels are associated with higher risk of type 2 diabetes, but it is unknown if the association is causal. We investigated common (>5%) genetic variants in the fetuin-A gene (AHSG) fetuin-A levels, fasting glucose, and risk of type 2 diabetes. RESEARCH DESIGN AND METHODS Genetic variation, fetuin-A levels, and fasting glucose were assessed in 2,893 Caucasian and 542 African American community-living individuals 65 years of age or older in 1992–1993. RESULTS Common AHSG variants (rs4917 and rs2248690) were strongly associated with fetuin-A concentrations (P < 0.0001). In analyses of 259 incident cases of type 2 diabetes, the single nucleotide polymorphisms (SNPs) were not associated with diabetes risk during follow-up and similar null associations were observed when 579 prevalent cases were included. As expected, higher fetuin-A levels were associated with higher fasting glucose concentrations (1.9 mg/dL [95% CI, 1.2–2.7] higher per SD in Caucasians), but Mendelian randomization analyses using both SNPs as unbiased proxies for measured fetuin-A did not support an association between genetically predicted fetuin-A levels and fasting glucose (−0.3 mg/dL [95% CI, −1.9 to 1.3] lower per SD in Caucasians). The difference between the associations of fasting glucose with actual and genetically predicted fetuin-A level was statistically significant (P = 0.001). Results among the smaller sample of African Americans trended in similar directions but were statistically insignificant. CONCLUSIONS Common variants in the AHSG gene are strongly associated with plasma fetuin-A concentrations, but not with risk of type 2 diabetes or glucose concentrations, raising the possibility that the association between fetuin-A and type 2 diabetes may not be causal

Total and High-Molecular-Weight Adiponectin and Risk of Incident Diabetes in Older People

OBJECTIVE To delineate the associations of total adiponectin, high-molecular-weight (HMW) adiponectin, and the HMW-to-total adiponectin ratio with diabetes in older adults. RESEARCH DESIGN AND METHODS Total and HMW adiponectin were measured in a population-based study of older adults. The relations of total adiponectin, HMW adiponectin, and their ratio with incident diabetes (n = 309) were assessed in 3,802 individuals. RESULTS Total and HMW adiponectin were highly correlated (r = 0.94). Analysis using cubic splines revealed that the associations between total and HMW adiponectin and new-onset diabetes were not linear. Specifically, after adjustment for confounders, there were similar inverse relationships for total (hazard ratio per SD 0.49 [95% CI 0.39–0.63]) and HMW adiponectin (0.42 [0.32–0.56]) with diabetes up to values of 20 and 10 mg/L, respectively, above which the associations plateaued. These associations persisted after adjustment for potential mediators (blood pressure, lipids, C-reactive protein, and homeostasis model assessment of insulin resistance [HOMA-IR]). There was, however, evidence of interaction by HOMA-IR in the lower range of adiponectin, with stronger inverse associations among insulin-sensitive than insulin-resistant participants. HMW-to-total adiponectin ratio showed a linear adjusted association with outcome, but this was abolished by inclusion of mediating variables. CONCLUSIONS In this older cohort, increasing concentrations of total and HMW adiponectin were associated with comparably lower risks of diabetes, but these associations leveled off with further increases above concentrations of 20 and 10 mg/L, respectively. The more pronounced risk decreases at the lower range among participants without insulin resistance support a role for adiponectin that is independent of baseline hyperinsulinemia, but this will require further investigation

Hemoglobin A1c and Arterial and Ventricular Stiffness in Older Adults

Objective: Arterial and ventricular stiffening are characteristics of diabetes and aging which confer significant morbidity and mortality; advanced glycation endproducts (AGE) are implicated in this stiffening pathophysiology. We examined the association between HbA1c, an AGE, with arterial and ventricular stiffness measures in older individuals without diabetes. Research Design & Methods: Baseline HbA1c was measured in 830 participants free of diabetes defined by fasting glucose or medication use in the Cardiovascular Health Study, a population-based cohort study of adults aged ≥65 years. We performed cross-sectional analyses using baseline exam data including echocardiography, ankle and brachial blood pressure measurement, and carotid ultrasonography. We examined the adjusted associations between HbA1c and multiple arterial and ventricular stiffness measures by linear regression models and compared these results to the association of fasting glucose (FG) with like measures. Results: HbA1c was correlated with fasting and 2-hour postload glucose levels (r = 0.21; p<0.001 for both) and positively associated with greater body-mass index and black race. In adjusted models, HbA1c was not associated with any measure of arterial or ventricular stiffness, including pulse pressure (PP), carotid intima-media thickness, ankle-brachial index, end-arterial elastance, or left ventricular mass (LVM). FG levels were positively associated with systolic, diastolic and PP and LVM. Conclusions: In this sample of older adults without diabetes, HbA1c was not associated with arterial or ventricular stiffness measures, whereas FG levels were. The role of AGE in arterial and ventricular stiffness in older adults may be better assessed using alternate AGE markers