Left ventricular hypertrophy is often found very early in the course of hypertension. It is not known whether increased left ventricular mass contributes to the pathogenesis of hypertension. The ...purpose of this study was to examine the impact of left ventricular mass and other echocardiographically assessed cardiac structural features on the incidence of hypertension.
Subjects for this investigation included participants in the Framingham Heart Study and the Framingham Offspring Study who were normotensive at the baseline examination (systolic blood pressure, < 140 mm Hg; diastolic blood pressure, < 90 mm Hg; not receiving antihypertensive medications) and free of coronary heart disease, congestive heart failure, valvular heart disease, hypertrophic cardiomyopathy, diabetes mellitus, and renal insufficiency. The study sample included 1121 men (mean age, 44.4 years) and 1559 women (mean age, 45.6 years). Four years after the baseline examination, 202 men (18.0%) and 257 women (16.5%) were hypertensive (systolic blood pressure, > or = 140 mm Hg; diastolic blood pressure, > or = 90 mm Hg; or use of antihypertensive medications). Baseline echocardiographic left ventricular mass (P = .01) and the sum of septal and posterior left ventricular wall thicknesses (P = .02) were associated with progression to hypertension. After adjusting for sex, baseline age, systolic and diastolic blood pressures, body mass index, alcohol intake, and systolic blood pressure from an examination 8 years earlier, the odds ratio for developing hypertension for a 1-SD increment in left ventricular mass index was 1.20 (95% confidence interval, 1.04 to 1.39), and the odds ratio for a 1-SD increment in left ventricular wall thickness was 1.16 (95% confidence interval, 1.02 to 1.33).
In these normotensive adults, increased left ventricular mass and wall thickness were associated with the development of hypertension. Further studies are warranted to examine the utility of echocardiography in determining the need for antihypertensive therapy and to assess the effect of earlier intervention on the course of progression to hypertension.
Obstructive sleep apnea (OSA) is a common heritable disorder displaying marked sexual dimorphism in disease prevalence and progression. Previous genetic association studies have identified a few ...genetic loci associated with OSA and related quantitative traits, but they have only focused on single ethnic groups, and a large proportion of the heritability remains unexplained. The apnea-hypopnea index (AHI) is a commonly used quantitative measure characterizing OSA severity. Because OSA differs by sex, and the pathophysiology of obstructive events differ in rapid eye movement (REM) and non-REM (NREM) sleep, we hypothesized that additional genetic association signals would be identified by analyzing the NREM/REM-specific AHI and by conducting sex-specific analyses in multiethnic samples. We performed genome-wide association tests for up to 19,733 participants of African, Asian, European, and Hispanic/Latino American ancestry in 7 studies. We identified rs12936587 on chromosome 17 as a possible quantitative trait locus for NREM AHI in men (N = 6,737; P = 1.7 × 10
) but not in women (P = 0.77). The association with NREM AHI was replicated in a physiological research study (N = 67; P = 0.047). This locus overlapping the RAI1 gene and encompassing genes PEMT1, SREBF1, and RASD1 was previously reported to be associated with coronary artery disease, lipid metabolism, and implicated in Potocki-Lupski syndrome and Smith-Magenis syndrome, which are characterized by abnormal sleep phenotypes. We also identified gene-by-sex interactions in suggestive association regions, suggesting that genetic variants for AHI appear to vary by sex, consistent with the clinical observations of strong sexual dimorphism.
Elevated low-density lipoprotein cholesterol (LDL-C) levels are a major cardiovascular disease risk factor. Genetic factors are an important determinant of LDL-C levels.
To identify single nucleotide ...polymorphisms associated with LDL-C and subclinical coronary atherosclerosis, we performed a genome-wide association study of LDL-C in 841 asymptomatic Amish individuals aged 20 to 80 years, with replication in a second sample of 663 Amish individuals. We also performed scanning for coronary artery calcification (CAC) in 1018 of these individuals.
From the initial genome-wide association study, a cluster of single nucleotide polymorphisms in the region of the apolipoprotein B-100 gene (APOB) was strongly associated with LDL-C levels (P < 10(-68)). Additional genotyping revealed the presence of R3500Q, the mutation responsible for familial defective apolipoprotein B-100, which was also strongly associated with LDL-C in the replication sample (P < 10(-36)). The R3500Q carrier frequency, previously reported to be 0.1% to 0.4% in white European individuals, was 12% in the combined sample of 1504 Amish participants, consistent with a founder effect. The mutation was also strongly associated with CAC in both samples (P < 10(-6) in both) and accounted for 26% and 7% of the variation in LDL-C levels and CAC, respectively. Compared with noncarriers, R3500Q carriers on average had LDL-C levels 58 mg/dL higher, a 4.41-fold higher odds (95% confidence interval, 2.69-7.21) of having detectable CAC, and a 9.28-fold higher odds (2.93-29.35) of having extensive CAC (CAC score ≥400).
The R3500Q mutation in APOB is a major determinant of LDL-C levels and CAC in the Amish.
BACKGROUND:Gait speed predicts functional decline, disability, and death and is considered a biomarker of biological aging. Changes in gait speed in persons aging with HIV may provide an important ...method of gauging health and longevity in an under assessed population. The objective of this study was to evaluate and quantify the rate of gait speed decline in HIV-infected (HIV) men compared with HIV-uninfected (HIV) men.
METHODS:The study was nested in the Multicenter AIDS Cohort Study. The primary outcome was usual gait speed in meters per second measured between 2007 and 2013. Differences in the rate of gait speed decline and the incidence of clinically slow gait (<1.0 m/s) were assessed using multivariate linear regression models and Cox proportional hazards models, respectively.
RESULTS:A total of 2025 men (973 HIV and 1052 HIV) aged 40 years and older contributed 21,187 person-visits (9955 HIV and 11,232 HIV) to the analysis. Average gait speeds at the age 50 years were 1.24 and 1.19 m/s in HIV and HIV men, respectively (P < 0.001). In fully adjusted models, gait speed decline averaged 0.009 m/s per year after age 50 years (P < 0.001); this decline was 0.025 m/s per year greater in HIV men (P < 0.001). Moreover, HIV men had a 57% greater risk of developing clinically slow gait (adjusted hazard ratio = 1.57, 95% confidence interval1.27 to 1.91).
CONCLUSIONS:These findings indicate a faster rate of functional decline in HIV-infected men, suggesting greater risks of disability and death with advancing age.
The goal of this study was to examine the cross-sectional associations of cardiovascular risk factors with left ventricular (LV) geometry and systolic function measured by cardiac magnetic resonance ...imaging (MRI) in the Multiethnic Study of Atherosclerosis (MESA).
Cardiovascular risk factors including hypertension, smoking, and obesity are known to be associated with increased LV mass, but less is known about the association of risk factors with LV systolic function, particularly in populations without clinical cardiovascular disease.
Participants were from 4 racial/ethnic groups and were free of clinical cardiovascular disease. Blood pressure, health habits, body mass index, lipid levels, and glucose abnormalities were assessed and MRI exams performed at baseline (n = 4,869). Multivariable linear regression was used to model the association of risk factors with LV mass, end-diastolic volume, stroke volume, ejection fraction, and cardiac output.
The mean age was 62 years, and 52% of the participants were women. After adjustment for sociodemographic variables and height, higher systolic blood pressure and body mass index were associated with larger LV mass and volumes. Current smoking and diabetes were associated with greater LV mass (+7.7 g, 95% confidence interval CI +5.5 to +9.9 and +3.5 g, 95% CI +1.2 to +5.8, respectively), and with lower stroke volume (-1.9 ml, 95% CI -3.3 to -0.5 and -4.5 ml, 95% CI -6.0 to -3.0, respectively) and lower ejection fraction (-1.6%, 95% CI -2.1 to -1.0 and -0.8%, 95% CI -1.5 to -0.2, respectively).
In this cohort free of clinical cardiovascular disease, modifiable risk factors were associated with subclinical alterations in LV size and systolic function as detected by cardiac MRI.
Abstract
Funding Acknowledgements
Type of funding sources: None.
BACKGROUND
Although endogenous sex hormones influence both left atrial (LA) and left ventricular (LV) structure in peri-menopausal ...women, no study has ever evaluated the interaction between sex hormones levels and the left atrioventricular coupling.
PURPOSE
This study aimed to assess the prognostic value of a left atrioventricular coupling index (LACI) in pre- and post-menopausal women without history of CVD at baseline.
METHODS
In all women participating in the Multi-Ethnic Study of Atherosclerosis (MESA) with baseline cardiovascular magnetic resonance (CMR) study, LACI was measured as the ratio of the LA end-diastolic volume divided by the LV end-diastolic volume. Cox proportional hazard models were used to assess the association between LACI and the outcomes of atrial fibrillation (AF), heart failure (HF), coronary heart disease (CHD) death, and hard CVD defined by myocardial infarction, resuscitated cardiac arrest, stroke, or CHD death. In multivariable analyses, the associations between LACI and the time-to-event were evaluated, adjusting for demographics, traditional cardiovascular risk factors, menopausal status and sex hormone levels.
RESULTS
Among the 2,087 women (61.2 ± 10.1 years), 485 cardiovascular events were observed during mean follow-up period of 13.2 ± 3.3 years. Greater LACI was independently associated with AF (HR 1.70; 95% CI 1.51-1.90), HF (HR 1.62; 95% CI 1.33-1.97), CHD death (HR 1.36; 95% CI 1.10-1.68), and hard CVD (1.30; 95% CI 1.13-1.51, all p < 0.001). Adjusted models with LACI showed significant improvement in model discrimination and reclassification compared to currently used standard models to predict the incidences of AF (C-statistic: 0.82 vs. 0.79; NRI = 0.325; IDI = 0.036), HF (C-statistic: 0.84 vs. 0.81; NRI = 0.571; IDI = 0.023), CHD death (C-statistic: 0.87 vs. 0.85; NRI = 0.506; IDI = 0.012), and hard CVD (C-statistic: 0.78 vs. 0.76; NRI = 0.229; IDI = 0.012). The prognostic value of LACI was homogeneous in both pre- and post-menopausal women with a better discrimination and reclassification compared to individual LA or LV parameters.
CONCLUSIONS
In a multi-ethnic population of pre- and post-menopausal women, LACI is an independent predictor of HF, AF, CHD death and hard CVD. In both pre- and post-menopausal women, LACI has an incremental prognostic value to predict cardiovascular events over traditional risk factors and sex hormone levels.
ClinicalTrials.gov Identifier: NCT00005487 Abstract Figure. Kaplan-Meier curves by LACI terciles Abstract Figure. Kaplan-Meier curves by LACI and Menop.
Pulmonary arterial hypertension (PAH) is a progressive disease that causes exercise limitation, heart failure, and death. We aimed to determine the safety and efficacy of aspirin and simvastatin in ...PAH.
We performed a randomized, double-blind, placebo-controlled 2×2 factorial clinical trial of aspirin and simvastatin in patients with PAH receiving background therapy at 4 centers. A total of 92 patients with PAH were to be randomized to aspirin 81 mg or matching placebo and simvastatin 40 mg or matching placebo. The primary outcome was 6-minute walk distance at 6 months. Sixty-five subjects had been randomized when the trial was terminated by the Data Safety and Monitoring Board after an interim analysis showed futility in reaching the primary end point for simvastatin. After adjustment for baseline 6-minute walk distance, there was no significant difference in the 6-minute walk distance at 6 months between aspirin (n=32) and placebo (n=33; placebo-corrected difference −0.5 m, 95% confidence interval −28.4 to 27.4 m; P=0.97) or between simvastatin (n=32) and placebo (n=33; placebo-corrected difference −27.6 m, 95% confidence interval −59.6 to 4.3 m; P=0.09). There tended to be more major bleeding episodes with aspirin than with placebo (4 events versus 1 event, respectively; P=0.17).
Neither aspirin nor simvastatin had a significant effect on the 6-minute walk distance, although patients randomized to simvastatin tended to have a lower 6-minute walk distance at 6 months. These results do not support the routine treatment of patients with PAH with these medications.
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