Jordan Tanley, Byron C. Jaeger, Haiying Chen
et al.
Abstract INTRODUCTION Subclinical cardiovascular disorders may be differentially associated with cognitive function, decline, and impairment and point to pathways linking vascular disorders to dementia. METHODS The Multi‐Ethnic Study of Atherosclerosis (MESA) collected detailed subclinical vascular measures at baseline in 6814 participants with follow‐up clinical examinations over 20 years. Baseline subclinical vascular measures aggregated into four uncorrelated factor composites: atherosclerosis, arteriosclerosis, blood pressure, and cardiac function. Cognitive performance was measured 10 years after baseline, repeated twice over the subsequent decade, along with detailed cognitive testing and adjudication. RESULTS Higher baseline arteriosclerosis and atherosclerosis scores predicted greater cognitive decline, lower performance across multiple domains, and higher odds of mild cognitive impairment and dementia 20 years later. Associations were weaker for cardiac function and blood pressure composites. Stratified analyses confirmed generalizability across subgroups. DISCUSSION Arteriosclerosis and atherosclerosis were more consistently associated with cognitive impairment and decline than cardiac function and blood pressure in a diverse population over 20 years. Highlights Subclinical factor relationships varied by cognitive domain and race/ethnicity. These observed associations were independent of clinical risk for dementia. Arteriosclerosis most consistently associated with cognitive function and decline.
Rithvik Swamynathan, Vinithra Varadarajan, Hieu Nguyen
et al.
Background. Chronic inflammation is associated with incident cardiovascular events. We study the association between biomarkers of inflammation and subclinical vascular dysfunction measured as proximal aortic stiffness. Methods. MRI imaging was performed in the Multi-Ethnic Study of Atherosclerosis (MESA) at baseline (2000) and at the 10-year follow-up. Aortic arch pulse wave velocity (PWV) and ascending and descending aorta distensibility (AAD, DAD) were measured in 1223 asymptomatic individuals at both exams. Linear regression was used to study the association of baseline inflammation—C-reactive protein (CRP), interleukin-6 (IL6), and fibrinogen (Fib)—with baseline and 10-year changes in aortic stiffness (PWV, AAD, DAD). Results. The mean age of the participants was 59 ± 9 years, 47.8% of them were men, 32.6% were hypertensive at baseline, and 7.6% were diabetic. At baseline and follow-up, the mean AAD values were, respectively, 1.73 × 10−3 mmHg−1 and 1.57 × 10−3 mmHg−1, the mean DAD values were 2.19 × 10−3 mmHg−1 and 1.99 × 10−3 mmHg−1, and the mean PWV values were 8.10 m/s and 8.99 m/s. At baseline, the AAD (in 10−3 mmHg−1) and DAD (in 10−3 mmHg−1) were inversely associated with CRP (in mg/L) (AAD coeff: −0.047, p-value: 0.011, DAD coeff: −0.068, p-value: <0.001) and IL6 (in pg/mL) (AAD coeff: −0.098, p-value: 0.003, DAD coeff: −0.14, p-value: <0.001) in a univariable analysis but not after adjustment for demographic variables or cardiovascular risk factors. The baseline DAD was inversely associated with Fib (in mg/dL) (coeff: −0.334, p-value: 0.001). The baseline PWV (in m/s) was positively associated with IL6 (in pg/mL) in a univariable analysis (coeff: 0.054, p-value: 0.014). In a longitudinal analysis, the 10-year changes in DAD were inversely associated with CRP, even after adjustment for demographics and risk factors (DAD coeff: −0.08, p-value 0.044). Conclusions. Higher CRP levels at baseline were independently associated with a 10-year increase in aortic stiffness, measured as decreased aortic distensibility.
Corey E. Ventetuolo, Grayson L. Baird, R. Graham Barr
et al.
Abstract Rationale Recent studies have focused on the role of female sex and estradiol (E2) in pulmonary arterial hypertension (PAH), but it is not known whether sex hormones are risk factors for PAH in men. Objectives We performed a case-control study to determine whether hormone levels (E2, dehydroepiandrosterone-sulfate [DHEA-S], and testosterone) are associated with PAH in men. Methods Plasma sex hormone levels in men with idiopathic, heritable, or connective tissue disease–associated PAH were compared with those from age- and body mass index–matched men without clinical cardiovascular disease. Measurements and Main Results There were 23 cases with PAH (70% had idiopathic PAH, 65% were functional class III/IV) and 67 control subjects. Higher E2 and E2/testosterone levels were associated with the risk of PAH (odds ratio per 1 ln[E2:testosterone], 6.0; 95% confidence interval, 2.2–16.4; P = 0.001), whereas higher levels of DHEA-S were associated with a reduced risk (odds ratio per 1 ln[DHEA-S], 0.1; 95% confidence interval, 0.0–0.3; P = 0.001). E2 and DHEA-S levels were strong predictors of case status (C statistic for both, 0.82) but testosterone was not (C statistic, 0.53). Higher levels of E2 were associated with shorter 6-minute-walk distances (P = 0.03), whereas higher levels of DHEA-S were associated with lower right atrial pressure (P = 0.02) and pulmonary vascular resistance (P = 0.01) in men with PAH. Conclusions Higher levels of E2 and lower levels of DHEA-S were associated with PAH in men. Sex-based differences in sex hormone processing and signaling may contribute to unique phenotypes in pulmonary vascular disease.
Kiarri N. Kershaw, Abbi D. Lane-Cordova, Mercedes R. Carnethon
et al.
Abstract BACKGROUND Endothelial dysfunction may represent an important link between chronic stress and cardiovascular disease (CVD) risk. However, few studies have examined the impact of chronic stress on endothelial dysfunction. The purpose of this study was to examine whether chronic stress was associated with flow-mediated dilation (FMD) and 2 biomarkers of endothelial dysfunction (intercellular adhesion molecule-1 (ICAM-1) and E-selectin) in a multiethnic sample of adults (ages 45–84 years). METHODS Data come from the baseline examination of Multi-Ethnic Study of Atherosclerosis participants. Chronic stress was assessed based on self-report of the presence and severity of ongoing problems in 5 domains. FMD was obtained using high-resolution ultrasound; biomarkers were assayed in different subsets of participants. RESULTS Higher chronic stress was associated with lower absolute FMD (mm FMD) in models adjusted for demographic and socioeconomic characteristics (0.169mm in high-stress participants vs. 0.178 and 0.179mm in medium and low-stress participants; P for trend = 0.04). This association remained unchanged with further adjustment for behavioral and biological CVD risk factors. Higher stress was related to higher ICAM-1 in models adjusted for sociodemographic characteristics and biological risk factors (P for trend = 0.005), but this association attenuated with adjustment for cigarette smoking (P for trend = 0.07). Chronic stress was not associated with E-selectin. CONCLUSIONS Our findings suggest chronic stress is related to endothelial dysfunction, possibly in part through other stress-associated CVD risk factors such as cigarette smoking.
Linn Beate Strand, Mercedes Carnethon, Mary Lou Biggs
et al.
OBJECTIVE We examined the associations of symptoms of sleep-disordered breathing (SDB), which was defined as loud snoring, stopping breathing for a while during sleep, and daytime sleepiness, and insomnia with glucose metabolism and incident type 2 diabetes in older adults. RESEARCH DESIGN AND METHODS Between 1989 and 1993, the Cardiovascular Health Study recruited 5,888 participants ≥65 years of age from four U.S. communities. Participants reported SDB and insomnia symptoms yearly through 1989–1994. In 1989–1990, participants underwent an oral glucose tolerance test, from which insulin secretion and insulin sensitivity were estimated. Fasting glucose levels were measured in 1989–1990 and again in 1992–1993, 1994–1995, 1996–1997, and 1998–1999, and medication use was ascertained yearly. We determined the cross-sectional associations of sleep symptoms with fasting glucose levels, 2-h glucose levels, insulin sensitivity, and insulin secretion using generalized estimated equations and linear regression models. We determined the associations of updated and averaged sleep symptoms with incident diabetes in Cox proportional hazards models. We adjusted for sociodemographics, lifestyle factors, and medical history. RESULTS Observed apnea, snoring, and daytime sleepiness were associated with higher fasting glucose levels, higher 2-h glucose levels, lower insulin sensitivity, and higher insulin secretion. The risk of the development of type 2 diabetes was positively associated with observed apnea (hazard ratio [HR] 1.84 [95% CI 1.19–2.86]), snoring (HR 1.27 [95% CI 0.95–1.71]), and daytime sleepiness (HR 1.54 [95% CI 1.13–2.12]). In contrast, we did not find consistent associations between insomnia symptoms and glucose metabolism or incident type 2 diabetes. CONCLUSIONS Easily collected symptoms of SDB are strongly associated with insulin resistance and the incidence of type 2 diabetes in older adults. Monitoring glucose metabolism in such patients may prove useful in identifying candidates for lifestyle or pharmacological therapy. Further studies are needed to determine whether insomnia symptoms affect the risk of diabetes in younger adults.