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Abstract-Although heat shock proteins (Hsp's) are present in the sera of healthy individuals and at elevated levels in subjects with early cardiovascular disease, their physiologic role in and value for predicting the development and/or progression of atherosclerosis have not been evaluated. Serum was obtained from 218 subjects with established hypertension (diastolic pressure Ͼ95 mm Hg) before their enrollment in the European Lacidipine Study on Atherosclerosis. Hsp60 and Hsp70, and anti-human Hsp60, anti-human Hsp70, and anti-mycobacterial Hsp65 antibody levels were measured by enzyme immunoassay. As an indicator of the presence/progression of atherosclerosis, the means of the maximum intima-media (I-M) thicknesses in the far walls of common carotid arteries and bifurcations (CBM max ) were determined by ultrasonography at the time of enrollment and 4 years afterward. Increases in I-M thicknesses at follow-up were less prevalent in subjects having high serum Hsp70 levels (75th percentile) at the time of enrollment (odds ratio, 0.42; 95% confidence interval [CI], 0.22 to 0.8, Pϭ0.008). Although a similar trend was observed for serum Hsp60 levels, this was not statistically significant (odds ratio, 0.6; 95% CI, 0.32 to 1.11, Pϭ0.10).There was no relation between anti-Hsp antibody levels and changes in I-M thicknesses. The relation between Hsp70 levels and changes in I-M thickness was independent of age, atenolol or lacidipine treatment, smoking habits, and blood lipid levels. These findings indicate that circulating Hsp70 levels predict the development of atherosclerosis in subjects with established hypertension, and an intriguing possibility is that Hsp70 protects against or modifies the progression of atherosclerosis in this subject group.

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Background: Lifestyle modifications have been recommended as the initial treatment strategy for lowering high blood pressure (BP). However, evidence for the efficacy of exercise and weight loss in the management of high BP remains controversial. Methods:One hundred thirty-three sedentary, overweight men and women with unmedicated high normal BP or stage 1 to 2 hypertension were randomly assigned to aerobic exercise only; a behavioral weight management program, including exercise; or a waiting list control group. Before and following treatment, systolic and diastolic BPs were measured in the clinic, during daily life, and during exercise and mental stress testing. Hemodynamic measures and metabolic functioning also were assessed.Results: Although participants in both active treatment groups exhibited significant reductions in BP relative to controls, those in the weight management group generally had larger reductions. Weight management was associated with a 7-mm Hg systolic and a 5-mm Hg diastolic clinic BP reduction, compared with a 4-mm Hg systolic and diastolic BP reduction associated with aerobic exercise; the BP for controls did not change. Participants in both treatment groups also displayed reduced peripheral resistance and increased cardiac output compared with controls, with the greatest reductions in peripheral resistance in those in the weight management group. Weight management participants also exhibited significantly lower fasting and postprandial glucose and insulin levels than participants in the other groups.Conclusions: Although exercise alone was effective in reducing BP, the addition of a behavioral weight loss program enhanced this effect. Aerobic exercise combined with weight loss is recommended for the management of elevated BP in sedentary, overweight individuals. Med. 2000;160:1947-1958 H YPERTENSION IS a major health problem in this country, affecting more than 43 million people in the United States. Arch Intern1 Hypertension is among the most common reasons for outpatient visits.2 Despite this, blood pressure (BP) control is often inadequate. 3Although BP can be lowered pharmacologically in hypertensive individuals, 4,5 antihypertensive medications are not effective for everyone, may be costly, and may induce adverse effects 6-9 that impair quality of life and reduce adherence. Moreover, abnormalities associated with hypertension, such as insulin resistance and lipemia, may persist or may even be exacerbated by some antihypertensive medications.10-13 As a result, nonpharmacological approaches to the treatment of hypertension have received growing attention.The 1997 report 5 of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure recommends that lifestyle modifications be the initial treatment strategy for lowering high BP. Despite these recommendations, however, empirical data supporting the efficacy of exercise and weight loss in the management of hypertension are relatively limited. Numerous observational studies [14][15][16] have de...

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Though aspirin is a well-established antiplatelet agent, the mechanisms of aspirin resistance remain poorly understood. Metabolomics allows for measurement of hundreds of small molecules in biological samples enabling detailed mapping of pathways involved in drug response. We defined the metabolic signature of aspirin exposure in subjects from the Heredity and Phenotype Intervention (HAPI) Heart Study. Many metabolites, including known aspirin catabolites, changed upon exposure to aspirin and pathway enrichment analysis identified purine metabolism as significantly affected by drug exposure. Further, purines were associated with aspirin response and poor responders had higher post-aspirin adenosine and inosine than good responders (N=76;p<4×10-3 both). Using our established “pharmacometabolomics-informs-pharmacogenomics” approach we identified genetic variants in adenosine kinase (ADK) associated with aspirin response. Combining metabolomics and genomics allowed for more comprehensive interrogation of mechanisms of variation in aspirin response - an important step toward personalized treatment approaches for cardiovascular disease.

Changes in depressive symptoms were not associated with changes in HbA1c or fasting glucose levels over a 1-year period in either patients with Type 1 or Type 2 diabetes.