Khaleghi, Mahyar

Background and Purpose— We investigated whether family history of stroke or coronary heart disease (CHD) is associated with presence of carotid artery stenosis (CAS). Methods— The study cohort included 864 patients (72±8 years; 68% men) with CAS and 1698 controls (61±11 years; 55% men) referred for noninvasive vascular testing. CAS was defined as ≥70% stenosis in the internal carotid artery on ultrasound or history of carotid revascularization. Controls did not have CAS or history of cerebrovascular disease or CHD. Family history of stroke and CHD was defined as having ≥1 first-degree relative who had stroke or CHD before age 65 years. Logistic regression analysis was used to evaluate whether family history of stroke or CHD was associated with presence of CAS, independent of conventional risk factors. Results— Family history of stroke and CHD was present more often in patients with CAS than in controls, with a resulting odds ratios (95% confidence interval) of 2.02 (1.61–2.53) and 2.01 (1.70–2.37), respectively. The associations remained significant after adjustment for age, sex, body mass index, smoking, diabetes mellitus, hypertension, and dyslipidemia; odds ratios: 1.41 (1.06–1.90) and 1.69 (1.35–2.10), respectively. A greater number of affected relatives with stroke or CHD was associated with higher odds of CAS; adjusted odds ratios: 1.25 (0.91–1.72) and 1.46 (1.14–1.89) versus 2.65 (1.35–5.40) and 2.13 (1.57–2.90) for patients with 1 and ≥2 affected relatives with stroke and CHD, respectively. Conclusions— Family history of stroke and of CHD were each associated with CAS, suggesting that shared genetic and environmental factors contribute to the risk of CAS.

We hypothesized that higher serum levels of N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) are associated with lower functional capacity in patients with peripheral arterial disease ([PAD] n = 481, mean age 67, 68% men). Functional capacity was quantified as distance walked on a treadmill for 5 minutes. Patients were divided into 3 groups according to the distance walked: >144 yards (group 1, n = 254); 60 to 144 yards (group 2, n = 80); <60 yards or did not walk (group 3, n = 147). The association between NT-pro-BNP levels and the ordinal 3-level walking distance was assessed using multivariable ordinal logistic regression analyses that adjusted for several possible confounding variables. Higher levels of NT-pro-BNP were associated with a lower ordinal walking category independent of possible confounders (odds ratio [OR] 1.51, 95% confidence interval [CI] 1.28-1.77; P < .001). In conclusion, higher levels of NT-pro-BNP are independently associated with lower functional capacity in patients with PAD and may be a marker of hemodynamic stress in these patients.

Context: Stress-mediated hypothalamic-pituitary-adrenal axis activation, regulated by arginine vasopressin (AVP), may have a role in the pathophysiology of metabolic syndrome (MetSyn). Objective: The objective of the study was to investigate whether plasma C-terminal provasopressin fragment (copeptin), a surrogate for circulating AVP, was associated with measures of insulin resistance and presence of MetSyn. Design, Setting, and Participants: This was a multicenter, community-based study, investigating novel biomarkers for vascular disease. Participants included 1293 African-Americans (AA) (64 ± 9 yr) and 1197 non-Hispanic whites (NHW) (59 ± 10 yr) belonging to hypertensive sibships. Main Outcome Measures: Plasma copeptin levels were measured by an immunoluminometric assay. MetSyn was defined per Adult Treatment Panel III criteria. Generalized estimating equations were used to assess whether plasma copeptin was associated with measures of insulin resistance and MetSyn. Results: The prevalence of MetSyn was 50% in AA and 49% in NHW. In each group, after adjustment for age and sex, plasma copeptin levels significantly correlated with body mass index, fasting plasma glucose and insulin, homeostasis model assessment of insulin resistance, triglycerides, and (inversely) high-density lipoprotein cholesterol (P &lt; 0.05 for each variable). In multivariable logistic regression models that adjusted for age, sex, smoking, statin use, serum creatinine, education, physical activity, and diuretic use, plasma copeptin levels in the highest quartile were associated with an increased odds ratio of having MetSyn compared with bottom quartile: odds ratio (95% confidence interval) in AA, 2.07 (1.45–2.95); in NHW, 1.74 (1.21–2.5). Conclusions: Our findings indicate a novel cross-sectional association between plasma copeptin and measures of insulin resistance and MetSyn.

Abstract Background: Higher plasma concentrations of soluble adhesion molecules have been shown to be associated with increased risk of cardiovascular events. We investigated the association of soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) with ankle-brachial index (ABI), a measure of peripheral arterial disease (PAD), in a biethnic cohort of adults without known coronary heart disease or stroke. Methods: Participants included 1102 blacks (mean age, 63 years; 74% women) and 1013 non-Hispanic whites (mean age, 58 years; 59% women) belonging to sibships ascertained on the basis of hypertension. We measured plasma concentrations of sICAM-1 and sVCAM-1 using high-sensitivity immunoassays and ABI using a standard protocol; PAD was defined as ABI &lt;0.9. We used generalized estimating equations to assess whether sICAM-1 and sVCAM-1 were associated with ABI and PAD, independently of conventional risk factors. Results: After adjustment for conventional risk factors, blacks with sICAM-1 and sVCAM-1 concentrations in the highest quartiles had lower ABIs than those in the lowest quartiles (mean ABI 1.02 vs 0.98, P = 0.007, vs 1.02 vs 0.99, P = 0.003, respectively). In multivariable logistic regression analysis, sICAM-1 and sVCAM-1 concentrations in the highest quartiles were each associated with a higher odds ratio of having PAD, compared with the lowest quartiles: odds ratio (95% CI): 5.2 (1.8–15.2) and 2.2 (1.0–4.8), respectively. In contrast, in non-Hispanic whites, sICAM-1 and sVCAM-1 concentrations were not associated with ABI or PAD. Conclusions: Higher sICAM-1 and sVCAM-1 concentrations were independently associated with lower ABI and PAD in blacks, but not in non-Hispanic whites.