The Effect of Salsalate Therapy on Endothelial Function in a Broad Range of Subjects

Background: Inflammation is fundamental to the development of atherosclerosis. We examined the effect of anti‐inflammatory doses of salicylate on endothelium‐dependent vasodilation, a biomarker of cardiovascular risk, in a broad range of subjects. Methods and Results: We performed a randomized, double‐blind, placebo‐controlled crossover trial evaluating the effects of 4 weeks of high‐dose salsalate (disalicylate) therapy on endothelium‐dependent flow‐mediated and endothelium‐independent vasodilation. Fifty‐eight subjects, including 17 with metabolic syndrome, 13 with atherosclerosis, and 28 healthy controls, were studied. Among all subjects, endothelium‐dependent flow‐mediated vasodilation decreased after salsalate compared with placebo therapy (P=0.01), whereas nitroglycerin‐mediated, endothelium‐independent vasodilation was unchanged (P=0.97). Endothelium‐dependent flow‐mediated vasodilation after salsalate therapy was impaired compared with placebo therapy in subjects with therapeutic salicylate levels (n=31, P0.2). Conclusions: Salsalate therapy, particularly when therapeutic salicylate levels are achieved, impairs endothelium‐dependent vasodilation in a broad range of subjects. These data raise concern about the possible deleterious effects of anti‐inflammatory doses of salsalate on cardiovascular risk. Clinical Trial Registration URL: www.clinicaltrials.gov. Unique Identifiers: NCT00760019 and NCT00762827

Insomnia symptoms and repressive coping in a sample of older Black and White women

BACKGROUND: This study examined whether ethnic differences in insomnia symptoms are mediated by differences in repressive coping styles. METHODS: A total of 1274 women (average age = 59.36 ± 6.53 years) participated in the study; 28% were White and 72% were Black. Older women in Brooklyn, NY were recruited using a stratified, cluster-sampling technique. Trained staff conducted face-to-face interviews lasting 1.5 hours acquiring sociodemographic data, health characteristics, and risk factors. A sleep questionnaire was administered and individual repressive coping styles were assessed. Fisher's exact test and Spearman and Pearson analyses were used to analyze the data. RESULTS: The rate of insomnia symptoms was greater among White women [74% vs. 46%; χ(2 )= 87.67, p < 0.0001]. Black women scored higher on the repressive coping scale than did White women [Black = 37.52 ± 6.99, White = 29.78 ± 7.38, F(1,1272 )= 304.75, p < 0.0001]. We observed stronger correlations between repressive coping and insomnia symptoms for Black [r(s )= -0.43, p < 0.0001] than for White women [r(s )= -0.18, p < 0.0001]. Controlling for variation in repressive coping, the magnitude of the correlation between ethnicity and insomnia symptoms was substantially reduced. Multivariate adjustment for differences in sociodemographics, health risk factors, physical health, and health beliefs and attitudes had little effect on the relationships. CONCLUSION: Relationships between ethnicity and insomnia symptoms are jointly dependent on the degree of repressive coping, suggesting that Black women may be reporting fewer insomnia symptoms because of a greater ability to route negative emotions from consciousness. It may be that Blacks cope with sleep problems within a positive self-regulatory framework, which allows them to deal more effectively with sleep-interfering psychological processes to stressful life events and to curtail dysfunctional sleep-interpreting processes

Sleep Apnea Is Associated with Subclinical Myocardial Injury in the Community. The ARIC-SHHS Study

Rationale: Obstructive sleep apnea (OSA) is associated with cardiovascular morbidity and mortality, although the underlying mechanisms are not well understood. Objectives: We aimed to determine whether more severe OSA, measured by the Respiratory Disturbance Index (RDI), is associated with subclinical myocardial injury and increased myocardial wall stress. Methods: A total of 1,645 participants (62.5 ± 5.5 yr and 54% women) free of coronary heart disease and heart failure and participating in both the Atherosclerosis Risk in the Communities and the Sleep Heart Health Studies underwent overnight polysomnography and measurement of high-sensitivity troponin T (hs-TnT) and N-terminal pro B-type natriuretic peptide (NT-proBNP). Measurements and Main Results: OSA severity was defined using conventional clinical categories: none (RDI ≤ 5), mild (RDI 5–15), moderate (RDI 15–30), and severe (RDI > 30). Hs-TnT, but not NT-proBNP, was associated with OSA after adjusting for 17 potential confounders (P = 0.02). Over a median of 12.4 (interquartile range, 11.6–13.1) years follow-up, hs-TnT was related to risk of death or incident heart failure in all OSA categories (P ≤ 0.05 in each category). Conclusions: In middle-aged to older individuals, OSA severity is independently associated with higher levels of hs-TnT, suggesting that subclinical myocardial injury may play a role in the association between OSA and risk of heart failure. OSA was not associated with NT-proBNP levels after adjusting for multiple possible confounders

Association between Glucose Metabolism and Sleep-disordered Breathing during REM Sleep

Rationale: Sleep-disordered breathing (SDB) has been associated with impaired glucose metabolism. It is possible that the association between SDB and glucose metabolism is distinct for non-REM versus REM sleep because of differences in sleep-state–dependent sympathetic activation and/or degree of hypoxemia. Objectives: To characterize the association between REM-related SDB, glucose intolerance, and insulin resistance in a community-based sample. Methods: A cross-sectional analysis that included 3,310 participants from the Sleep Heart Health Study was undertaken (53% female; mean age, 66.1 yr). Full montage home-polysomnography and fasting glucose were available on all participants. SDB severity during REM and non-REM sleep was quantified using the apnea–hypopnea index in REM (AHI(REM)) and non-REM sleep (AHI(NREM)), respectively. Fasting and 2-hour post-challenge glucose levels were assessed during a glucose tolerance test (n = 2,264). The homeostatic model assessment index for insulin resistance (HOMA-IR) was calculated (n = 1,543). Linear regression was used to assess the associations of AHI(REM) and AHI(NREM) with fasting and post-prandial glucose levels and HOMA-IR. Measurements and Main Results: AHI(REM) and AHI(NREM) were associated with fasting glycemia, post-prandial glucose levels, and HOMA-IR in models that adjusted for age, sex, race, and site. However, with additional adjustment for body mass index, waist circumference, and sleep duration, AHI(REM) was only associated with HOMA-IR (β = 0.04; 95% CI, 0.1–0.07; P = 0.01), whereas AHI(NREM) was only associated with fasting (β = 0.93; 95% CI, 0.14–1.72; P = 0.02) and post-prandial glucose levels (β = 3.0; 95% CI, 0.5–5.5; P = 0.02). Conclusions: AHI(REM) is associated with insulin resistance but not with fasting glycemia or glucose intolerance