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Data from epidemiologic studies document the role of clinically manifest diabetes mellitus as a powerful risk determinant for an array of atherosclerotic cardiovascular outcomes including coronary heart disease (CHD), stroke, and peripheral arterial disease, particularly in the elderly. Although dyslipidemias and hypertension are quite prevalent in persons with diabetes mellitus and contribute heavily to the underlying atherosclerotic process, other factors involving alternative pathogenetic mechanisms are necessary to explain for the dramatic acceleration of atherogenesis observed in this condition. Myocardial ischemia may be silent and myocardial infarction (MI) may be either painless or atypical in presentation which further complicates both the diagnostic and therapeutic management of CHD in older diabetic patients. MI, in this context, is confounded by dual prognostic disadvantages of higher risk for MI- related complications attributable to both advanced age and diabetes mellitus. Because available evidence has yet to demonstrate that control of hyperglycemia, either by oral agents or by insulin, effectively forestalls either the development or complications of atherosclerosis, preventive management in older patients with diabetes requires critical attention to correcting coexisting cardiovascular risk factors.

Body habitus changes among adult males from the normative aging study: relations to aging, smoking history and alcohol intake. Obes Res. 1995;3:435–446. The Normative Aging Study (NAS) recruited 2280 Boston area healthy males aged 21 to 80 in 1961 through 1970. Clinical exams have continued at 3‐ to 5‐year intervals. Obesity was not an exclusion criterion. Stability in weight and body habitus among 867 adult participants in the NAS was evaluated at 5‐and 15‐year follow‐ups. At study entry, age was linearly related to central adiposity [abdominal circumference (AC) and ratio of AC/Hip Breadth (HB)] throughout the entire age range (30 to 78 years) and linearly and quadratically related to weight (WT) and Body Mass Index (BMI) (kg/m2) with maximal values at age 50. Over 15 years, changes in adiposity were strongly related to age; the greatest increases were among those initially 30 to 44 years of age with decrements in several adiposity measures (BMI, AC) only among the oldest subjects (60+ at entry); significant quadratic effects of age for BMI (p<. 001), WT (p<. 02) and AC (p<. 01). There were major secular differences; men born later were heavier and fatter at the same ages as men born earlier. Men who gained (>1 BMI) were younger while men who lost (>1 BMI) had greater initial central adiposity than others. Smoking cessation was independently associated with increments in both central and peripheral adiposity. Moderate alcohol intake was associated with lower gains in AC/HB ratios at 15 years compared with little or high consumption. In general, aging was associated with trends towards central adiposity which tended to plateau or decrease at the oldest ages.

Various epidemiologic studies have linked an increase in serum uric acid level to an increased risk of coronary heart disease. The reasons for this finding are unclear. The authors examined the influence of a number of cardiovascular disease risk factors on serum uric acid level in 886 middle-aged and older men participating in the Normative Aging Study. The men were examined between 1987 and 1991. In a multivariate regression model predicting serum uric acid level, uric acid was positively associated with body mass index (weight (kg)/height (m)2 beta = 0.041 mg/dl per kg/m2, p = 0.003), abdomen: hip circumference ratio (beta = 1.88 mg/dl per cm/cm, p = 0.048), log alcohol intake (beta = 0.150 mg/dl per g/week, p = 0.0001), and log postcarbohydrate insulin level (beta = 0.157 mg/dl per log(microIU/ml), p = 0.005). Serum uric acid level was negatively associated with age (beta = -0.012 mg/dl per year of age, p = 0.017) and log physical activity (beta = -0.152 mg/dl per kcal/week, p = 0.0001). The data suggest that serum uric acid may be involved in the obesity-insulin resistance syndrome, which in turn may explain the relation of serum uric acid to coronary atherosclerosis.

Our objective was to identify biologic determinants of propranolol serum levels in 1308 patients after myocardial infarction (MI). Patients had had their MI within the previous month. A steady-state propranolol dosage of 40 mg every 8 hours produced a mean trough concentration of 42 ng/ml with extremely great (fiftyfold) interindividual variability. Univariate and multivariate analyses suggested that this variability was the result of many biologic factors. Serum levels were higher in women, in older patients, and in patients receiving concomitant therapy with other antiarrhythmic drugs. Serum levels were also higher in patients with elevated serum creatinine and lactate dehydrogenase levels. Serum levels were lower in black patients than in white patients. Also, serum levels in smokers were lower than those in nonsmokers, but only markedly so in the outpatient setting (6 months after the MI). The influence of sex and race on drug disposition has not previously been reported for β-blocking drugs. Although a genetic deficiency in the oxidative metabolism of propranolol has been indicated, the frequency distribution of serum propranolol levels did not demonstrate a bimodal distribution for genetically distinct populations.

This report describes the development of hypertension among 1,270 males (aged 23-80 years at the time of entry into the study) observed prospectively for 10 years who had a baseline blood pressure of less than 140/90 mmHg and who underwent baseline spirometry. Subjects were participants in the Normative Aging Study, a longitudinal study on aging initiated in 1961 at the Veterans Administration Outpatient Clinic in Boston, Massachusetts. Blood pressures were taken at five- and 10-year follow-up examinations. The age-adjusted incidence of hypertension during the follow-up period was found to be inversely related to forced vital capacity. Multiple logistic regression was employed to assess the relation of forced vital capacity to the subsequent development of hypertension after controlling for baseline levels of age, weight, cigarettes smoked per day, and systolic and diastolic blood pressures. Forced vital capacity was a statistically significant and negative predictor, indicating that lower values of forced vital capacity were associated with the subsequent development of hypertension. This was consistently found in several logistic regression analyses with a standardized odds ratio associated with forced vital capacity of approximately 0.7. Although the physiologic mechanism for this association is unknown, these findings may have importance in identifying subjects at risk and may also provide insight into disease pathogenesis.

The relation between the abdominal accumulation of body fat, total-body adiposity, and blood glucose level and the risk of non-insulin-dependent diabetes mellitus was evaluated prospectively among 1,972 male participants in the Department of Veterans Affairs Normative Aging Study cohort. The risk of non-insulin-dependent diabetes mellitus was assessed by means of the proportional hazards model; 226 cases of diabetes occurred among the 1,972 men (mean age at entry, 41.9 years; range, 22-80 years) over 35,496 person-years of observation. The relation of body mass index to diabetes risk was partly explained by body fat distribution; after adjusting for age, the ratio of abdominal circumference to hip breadth, and cigarette smoking, men in the top tertile for body mass index had a 1.3-fold greater risk of diabetes than did men in the lowest tertile (95% confidence interval 0.9-1.8). Moreover, after adjusting for age, body mass index, and cigarette smoking, men in the top tertile for the ratio of abdominal circumference to hip breadth had a 2.4-fold greater risk of diabetes than did men in the lowest tertile (95% confidence interval 1.7-3.7). When blood glucose was analyzed as a continuous outcome variable, the findings were consistent, i.e., a positive association with abdominal fat independent of total-body adiposity. These results confirm previous reports of a prospective relation between abdominal adiposity and the risk of diabetes and provide prospective evidence of a relation between blood glucose levels and both body fat distribution and obesity.

It is our central hypothesisthat periodontal diseases, which are chronic Gramnegative infections, represent a previously unrecognized risk factor for atherosclerosis and thromboembolic events. Previous studies have demonstrated an association between periodontal disease severity and risk of coronary heart disease and stroke. We hypothesize that this association may be due to an underlying inflammatory response trait, which places an individual at high risk for developing both periodontal disease and atherosclerosis. We further suggest that periodontal disease, once established, provides a biological burden of endotoxin (lipopolysaccharide) and inflammatory cytokines (especially TxA2, IL‐1β, PGE2, and TNF‐α) which serve to initiate and exacerbate atherogenesis' and thromboembolic events. A cohort study was conducted using combined data from the Normative Aging Study and the Dental Longitudinal Study sponsored by the United States Department of Veterans Affairs. Mean bone loss scores and worst probing pocket depth scores per tooth were measured on 1,147 men during 1968 to 1971. Information gathered during follow‐up examinations showed that 207 men developed coronary heart disease (CHD), 59 died of CHD, and 40 had strokes. Incidence odds ratios adjusted for established cardiovascular risk factors were 1.5, 1.9, and 2.8 for bone loss and total CHD, fatal CHD, and stroke, respectively. Levels of bone loss and cumulative incidence of total CHD and fatal CHD indicated a biologic gradient between severity of exposure and occurrence of disease. J Periodontol 1996;67:1123–1137.

Previous studies have suggested that excess body weight increases coronary disease risk by modification of the levels of other risk factors and in addition may contribute to overall risk independently. Few studies, however, have systematically characterized long-term change in risk factors with specific changes in overall weight while they have controlled for the effects of multiple potential confounders. Also, very little information is available on the differential impact of weight change on risk factor changes with advancing age. The present investigation used 15 years of longitudinal data collected on 1,396 men participating in the Veterans Administration Normative Aging Study in Boston, Massachusetts. Multiple regression analysis was used to predict change in each of eight putative coronary disease risk factors from change in weight and the interaction between weight change and age. These included blood pressure, serum cholesterol, triglycerides, fasting and two-hour postprandial blood glucose, uric acid, and forced vital capacity of the lungs. After controlling for initial levels of the risk factor, weight, age, and smoking status, change in weight remained a significant predictor of long-term change in each of the risk factors studied. In addition, the interaction between weight change and age was significant for fasting glucose, uric acid, and forced vital capacity, indicating that the effect of weight gain on uric acid and forced vital capacity was greater in younger men whereas the effect of weight gain on fasting glucose was greater in older men.

A total of 305 selected patients with chest pain syndromes were studied with both the two-step test and selective coronary cinearteriography. All patients were suspected clinically of having coronary artery disease. Subjects with positive responses were subdivided according to degree of ischemic R-ST depression, and those with negative responses according to immediate postexercise heart rate. Results of this study suggest that the diagnostic accuracy of a moderate stress test (such as the two-step) is greatly enhanced when postexercise heart rate, degree of R-ST depression, and presence of preexercise electrocardiographic abnormalities are considered. Retention of the two-step test as a screening procedure appears justified.

Background Increased concentrations of particles in air have been related to changes in inflammatory markers that in turn are hypothesized in mediating the particle effects on cardiovascular disease. The present work examined this association in an elderly cohort in the Greater Boston area and addresses the relative role of particles from different sources. Methods The study included 710 subjects, active members of the VA Normative Aging Study cohort with measurements of blood markers. Concentrations of particle number (PN), black carbon (BC), fine particulate matter (PM2.5), and sulphates were measured at a central site near the examination site. Results Positive associations were found between traffic-related particles (PN and BC) and inflammatory markers, but only suggestive associations were found with exposures to PM2.5 and sulphates. The particle effect on the inflammatory markers was greater among subjects older than 78 years and among obese. A suggestion for a greater effect of particles on inflammatory markers among GSTM1-null subjects and non-users of statin drugs was also seen. Conclusions The findings of the study support the hypothesis that particles can induce cardiovascular disease through inflammatory pathways, suggestive of a greater toxicity of traffic-related particles.

Supported by 5 T32 ES07069-22, 2 T32 ES07069-21, NIEHS ES00002, and EPAR827353 Recently, reduced heart rate variability (HRV), a marker of poor cardiac autonomic function, has been associated with air pollution, especially fine particulate matter (PM2.5). This study examined the relationship between alterations in HRV and ambient pollutants in 314 white male participants (mean age 72) from the Normative Aging Study in greater Boston, Massachusetts. Time domain (standard deviation of normal-to-normal (NN) intervals (SDNN), the square root of the mean of the squared differences between adjacent NN intervals (r-MSSD), triangular index), frequency domain (total power, power in high (HF) and low frequency (LF), LF/HF ratio) measures of HRV and other potential confounders (age, fasting blood glucose (FBG), smoking status (never/former/current), use of beta-blocker and angiotensin-converting enzyme inhibitor, room temperature) were collected from November 14, 2000 through April 16, 2002. 1-, 4- and 24-hour moving averages of air pollution (PM2.5, particle number, black carbon, NO2, SO2, CO, ozone) and weather data (temperature, relative humidity, barometric pressure) matched on the time of measuring electrocardiogram for each subjects were also obtained from the Massachusetts Department of Environmental Protection local monitoring site and from the Harvard School of Public Health monitoring site. For the r-MSSD, 11 subjects were excluded due to abnormal values. Log10 transformed HRV were used as response variables. After controlling for potential confounders, we found 16.23 (95 CI, 0.58 to 29.42 ) and 23.54 (8.13 to 36.37 ) decreases in the r-MSSD for interquartile increases in the 4-hour mean (15.9 ppb) and the 24-hour mean (16.6 ppb) ozone levels, respectively. Increments in 24-hour mean ozone levels were marginally associated with SDNN (-11.26 , 95 CI, -22.22 to 1.25 ), HF (-25.04 , -46.67 to 5.36 ), and LF (-22.38 , -40.90 to 1.95 ). Elevated particle numbers (18425/cm3 IQR) were marginally associated with SDNN (-12.21 , 95 CI -24.29 to 1.79 ), total power (-21.48 , -40.37 to 3.40 ) and HF (-29.26 , -51.99 to 4.22 ). In addition, we assessed the modifying effect of FBG on the association between ozone and HRV and found a significant and positive modifying effect of FBG. This means ozone may affect HRV most in those with normal FBG, but less in those with impaired FBG and least in diabetics. No association of HRV with PM2.5 was found. This study suggests that exposures to ozone are associated with decreased HRV.