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Biomedical subjects

W Kannel

Publications and source records attributed to W Kannel.

12 recordsLinked to original sources

Angiotensin receptor blockers: evidence for preserving target organs.

Hypertension is a major problem throughout the developed world. Although current antihypertensive treatment regimens reduce morbidity and mortality, patients are often noncompliant, and medications may not completely normalize blood pressure. As a result, current therapy frequently does not prevent or reverse the cardiovascular remodeling that often occurs when blood pressure is chronically elevated. Blockade of the renin-angiotensin system (RAS) is effective in controlling hypertension and treating congestive heart failure. Both angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) inhibit the activity of the RAS, but these two classes of antihypertensive medications have different mechanisms of action and different pharmacologic profiles. Angiotensin-converting enzyme inhibitors block a single pathway in the production of angiotensin II (Ang II). In addition, angiotensin I is not the only substrate for ACE. The ACE inhibitors also block the degradation of bradykinin that may have potential benefits in cardiovascular disease. Bradykinin is, however, the presumed cause of cough associated with ACE inhibitor therapy. Data from clinical trials on ACE inhibitors serve to support the involvement of the RAS in the development of cardiovascular disease. Angiotensin receptor blockers act distally in the RAS to block the Ang II type 1 (AT1) receptor selectively. Thus, ARBs are more specific agents and avoid many side effects. Experimental and clinical trials have documented the efficacy of ARBs in preserving target-organ function and reversing cardiovascular remodeling. In some instances, maximal benefit may be obtained with Ang II blockade using both ARBs and ACE inhibitors. This review describes clinical trials that document the efficacy of ARBs in protecting the myocardium, blood vessels, and renal vasculature.

Angiotensin Receptor Antagonists↗

Grip strength and the risk of developing radiographic hand osteoarthritis: results from the Framingham Study.

OBJECTIVE: In knees, quadriceps strength may protect against osteoarthritis (OA). Muscle activity is a major determinant of forces at the hand joints, and grip is a common task during which high muscle forces are sustained, especially at the proximal hand joints (metacarpophalangeal [MCP] joints and thumb base). This longitudinal study of radiographic hand OA examined the association between incident OA at different hand joints and maximal grip strength. METHODS: Four hand joint groups were studied: distal interphalangeal (DIP), proximal interphalangeal (PIP), MCP, and the base of the thumb (carpometacarpal and scaphotrapezial combined). Subjects were members of the Framingham OA Study who had a baseline radiograph in 1967-1969 and a followup radiograph in 1992-1993 (mean followup 24 years) and had no prevalent radiographic OA in any hand joint at baseline. Incident disease was defined as development of OA defined as a modified Kellgren/Lawrence grade of > or =2. Grip strength was measured in kilograms by dynamometer in 1958-1961 and again in 1960-1963, and the 2 measures were averaged and divided into sex-specific tertiles. Joint-based analysis was performed by adjusting for age, physical activity, and occupational category using the lowest grip strength tertile as the referent. RESULTS: Baseline and followup radiographs were obtained from 746 subjects. Of these, 453 subjects with no prevalent OA at baseline were eligible for analysis. In men, higher maximal grip strength was associated with an increased risk of OA in the PIP (highest tertile odds ratio [OR] 2.8 compared with lowest tertile, 95% confidence interval [95% CI] 1.2-6.7), MCP (highest tertile OR 2.9, 95% CI 1.1-7.4), and thumb base joints (highest tertile OR 2.8, 95% CI 1.1-7.4). In women, there was increased risk of OA in the MCP joints (highest tertile OR 2.7, 95% CI 1.1-6.4). CONCLUSION: Men with high maximal grip strength are at increased risk for the development of OA in the PIP, MCP, and thumb base joints, and women, in the MCP joints. No association was found between maximal grip strength and incident OA in the DIP joints of men or women.

Female↗

Benefits and adverse effects of weight loss. Observations from the Framingham Study.

OBJECTIVE: To identify the benefits and adverse effects of weight loss. DESIGN: Longitudinal, epidemiologic study in a defined population. PARTICIPANTS: Men and women (n = 2500) who were between 35 and 54 years old at baseline, followed for 20 years in Framingham, Massachusetts. MEASUREMENTS: Height, weight, lipid levels, blood pressure, smoking status, diet, physical activity, prevalent and incident cardiovascular disease, diabetes, other diseases, and mortality rate were assessed. RESULTS: Compared with those whose body mass index (BMI) or weight changed least, men and women who lost weight during a 10-year period were older, heavier, and had higher blood pressures and cholesterol levels initially but had the smallest gains in blood pressure and cholesterol levels. However, rates of cigarette smoking were higher, and rates of smoking cessation were lower. During 20 years of further follow-up, death rates were highest in those whose BMI decreased and in those with the highest BMI at study entry. Relative risks for death from cardiovascular disease, coronary heart disease, and all causes were significantly greater by 33% to 61% in men whose BMI decreased after adjusting for age and risk factors for cardiovascular disease. In women, weight loss and weight gain were associated with higher relative risks for cardiovascular disease and coronary heart disease, but only the 38% increase in total mortality rate among women who lost weight was statistically significant after adjusting for age. CONCLUSIONS: Weight loss was associated with improvements in blood pressure and cholesterol levels but also with continued cigarette smoking, prevalent and incident cardiovascular disease, diabetes mellitus, other diseases, and higher death rates. Leanness and maintenance of stable weight were beneficial to risk factors, and to the prevention of morbidity, and death.

Adult↗

High-normal blood pressure progression to hypertension in the Framingham Heart Study.

This study sought to determine if individuals with high-normal blood pressure (diastolic blood pressure of 85-89 mm Hg) progress to hypertension more frequently than those with normal blood pressure (diastolic blood pressure less than 85 mm Hg), thus advancing to a higher cardiovascular risk category. Individuals from the Framingham Heart Study were placed in normal and high-normal blood pressure categories and followed for 26 years for the development of hypertension. With hypertension defined as a diastolic blood pressure of 95 mm Hg or greater or the initiation of antihypertensive therapy, 23.6% of men and 36.2% of women with normal blood pressure developed hypertension compared with 54.2% of men and 60.6% of women with high-normal blood pressure. The relative risk for the development of hypertension associated with high-normal blood pressure was 2.25 for men (95% confidence interval [CI], 1.8-2.8; p less than 0.0001) and 1.89 for women (95% CI, 1.5-2.3; p less than 0.0001). The age-adjusted relative risks estimated by the proportional hazards model were 3.36 for men and 3.37 for women (p less than 0.001). Among those risk factors examined, baseline systolic and diastolic blood pressure, Metropolitan relative weight, and change in weight over time were significant predictors of future hypertension in men and women whose initial blood pressure was normal. For men with high-normal blood pressure, systolic blood pressure and change in weight were identified as risk factors for future hypertension. These results indicate that the probability of individuals with blood pressure in the high-normal range developing hypertension is twofold to threefold higher than in those with normal blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The prevalence of chondrocalcinosis in the elderly and its association with knee osteoarthritis: the Framingham Study.

Chondrocalcinosis and osteoarthritis (OA) both increase in prevalence with age, yet previous studies assessing their association have often been too small to adjust for age and have had biased selection of subjects. We assessed the prevalence of chondrocalcinosis and its link with OA in the Framingham Knee Osteoarthritis Study, a large population based study of the elderly. After controlling for age, we found a modestly increased rate of radiographic OA in those with chondrocalcinosis (relative risk = 1.52 (95% CI 1.22, 1.90). There was a similar link between chondrocalcinosis and severe radiographic OA (relative risk = 1.52). Chondrocalcinosis was positively associated with both symptomatic and asymptomatic radiographic OA. The proportion of radiographic OA potentially attributable to chondrocalcinosis was only 4.4%. Our results confirm that chondrocalcinosis is significantly associated with OA after controlling for age, but they also suggest that chondrocalcinosis and OA increase independently with age.

Aged↗

Body mass index and mortality among nonsmoking older persons. The Framingham Heart Study.

The relationship of weight at age 65 years and subsequent mortality was examined in a population of 1723 nonsmokers who were followed up from one to 23 years (mean, 9.5 years) during the Framingham Heart Study. In sex-specific proportional hazards analyses, risks of mortality were increased for men and women at the high and low extremes of body mass index, even when accounting for potential effects of excess weight on serum cholesterol level, blood glucose level, and systolic blood pressure. For those at the lower extreme of body mass index, the relative risk of death was almost twice as high in the years immediately after age 65 years as in later follow-up, suggesting that the increased early death rate was due to disease that was already present. At the upper extreme, risk of death was twofold over the entire follow-up period for persons with body mass indexes at or above the 70th percentile at both 55 and 65 years of age. We conclude that, even when accounting for cardiovascular risk factors, being overweight is a serious health problem for older people, especially for those with long-standing weight problems.

Aged↗

Hazards of obesity--the Framingham experience.

Measurements of height, weight, skinfolds and waist girth were used as indicators of general and regional obesity in the Framingham study population of 5,209 men and women. Mean values of cholesterol, blood pressure, blood glucose and uric acid increased with increasing body mass index (BMI). Weight gain was associated with increases and weight loss with decreases in these risk factors. Cigarette smoking was more prevalent in men and women with low quintile BMI. Upper quintile values of BMI, subscapular skinfolds, and waist girth were associated with increased relative risks of death from all causes, coronary heart disease (CHD) and cerebrovascular disease but relative risks for intermittent claudication were not increased. General and central obesity each made independent contributions to risk of CHD but central obesity was a better predictor in males. BMI, cholesterol, systolic blood pressure and blood glucose were significantly independent predictors of CHD. These data show that increased relative weight and central obesity are associated with elevated levels of risk factors, with increased incidence of cardiovascular disease and with increased death rates for all causes combined. Mortality rates are also increased among the leanest members of the population, especially among older men.

Adipose Tissue↗

Blood pressure experience and risk of cardiovascular disease in the elderly.

For the 1254 persons in the Framingham Heart Study who survived to age 65 without prior cardiovascular disease or prior use of antihypertensive medications, significant univariate correlates of the development of cardiovascular disease after age 65 included (1) the systolic blood pressure at age 65, (2) the average systolic blood pressure before age 65, and (3) the slope of blood pressure change up to age 65. After controlling for the systolic blood pressure at age 65, average pre-age 65 blood pressure remained significant (p less than 0.05) and the slope of the pre-age 65 blood pressure was marginally significant (p = 0.06). Even after controlling for the mean of up to three blood pressure measurements at age 65, an average systolic blood pressure of 160 mm Hg or greater before age 65 was an independently significant predictor of the post-age 65 development of cardiovascular disease (rate ratio = 1.79; 95% confidence interval = 1.04, 3.07). These data suggest that even after performing multiple measurements at a single examination, knowledge of past systolic blood pressure history, especially if it averages 160 mm Hg or greater, adds a small but statistically significant increment in predicting future cardiovascular disease in the elderly.

Adult↗