L.H. Kuller

Serum cholesterol, blood pressure and mortality : implications from a cohort of 361,662 men

The risks associated with various levels of serum cholesterol were determined by analysis of 6-year mortality in 361,662 men aged 35-57. Above the 20th percentile for serum cholesterol (greater than 181 mg/dl, greater than 4.68 mmol/l), coronary heart disease (CHD) mortality increased progressively; the relative risk was large (3.8) in the men with cholesterol levels above the 85th percentile (greater than 253 mg/dl, greater than 6.54 mmol/l). When men below the 20th cholesterol percentile were used as the baseline risk group, half of all CHD deaths were associated with raised serum cholesterol concentrations; half of these excess deaths were in men with cholesterol levels above the 85th percentile. For both CHD and total mortality, serum cholesterol was similar to diastolic blood pressure in the shape of the risk curve and in the size of the high-risk group. This new evidence supports the policy of a moderate fat intake for the general population and intensive treatment for those at high risk. There is a striking analogy between serum cholesterol and blood pressure in the epidemiological basis for identifying a large segment of the population (10-15%) for intensive treatment.

The Pittsburgh Insulin-dependent Diabetes Mellitus (IDDM) Morbidity and Mortality Study: Mortality Results

A follow-up study of 1966 patients with insulin-dependent diabetes mellitus (IDDM) who were diagnosed at Childrens Hospital of Pittsburgh (CHP) between 1950 and 1981 has been completed. The mean age of the population at follow-up was 21.2 yr with a mean duration of IDDM of 12.9 yr. Nine percent of the patients were deceased, a sevenfold excess in mortality compared with the U.S. population. The relative increase in mortality was greater for females than males and greater for blacks than whites. Before age 20, the primary excess in mortality was at onset of IDDM, or within 6 mo after onset, and was due to acute diabetic complications. After age 20, the annual mortality risk was approximately 2%, which was more than 20 times greater than for the U. S. population. Renal disease was responsible for the majority of these deaths. There was a reduced risk of dying for diabetic patients who were diagnosed between 1966 and 1971 compared with patients diagnosed during earlier years.

The epidemiology of quantitative ultrasound : A review of the relationships with bone mass, osteoporosis and fracture risk

Quantitative ultrasound (QUS) is a simple, inexpensive and non-invasive measure of bone which has been used in research settings for the prediction of osteoporosis. This review summarizes the current status of the epidemiology of QUS analysis, including its relationship with bone mineral density (BMD), risk of osteoporotic fracture and risk factors for osteoporosis. Although only moderately correlated with BMD, QUS appears to be as strong a predictor of osteoporotic fracture as BMD and may predict fracture independent of BMD. Risk factors for low QUS, including age, menopause, body composition and physical inactivity, seem to parallel those of low BMD. More longitudinal research is needed to confirm the clinical utility of QUS and more experimental and population-based studies are needed to determine whether the etiology of low QUS values is different from that of low bone mass.

The association of physical activity with obesity, fat distribution and glucose intolerance in Pima Indians

SummaryThe relationships between physical activity, obesity, fat distribution and glucose tolerance were examined in the Pima Indians who have the highest documented incidence of non-insulin-dependent diabetes. Fasting and 2-h post-load plasma glucose concentrations, body mass index, and waist-to-thigh circumference ratios were determined in 1054 subjects aged 15–59 years. Current (during the most recent calendar year) and historical (over a lifetime) leisure and occupational physical activity were determined by questionnaire. Current physical activity was inversely correlated with fasting and 2-h plasma glucose concentrations, body mass index and waist-to-thigh ratios for most sex-age groups even when diabetic subjects were excluded. Controlled for age, obesity and fat distribution, activity remained significantly associated with 2-h plasma glucose concentrations in males. In subjects aged 37–59 years, individuals with diabetes compared to those without reported significantly less leisure physical activity during the teenage years (median hours per week of activity, 9.1 vs 13.2 for men; 1.0 vs 2.2 for women). Controlled for body mass index, sex, age and waist-to-thigh ratio, subjects who reported low levels of historical leisure physical activity had a higher rate of diabetes than those who were more active. In conclusion, current physical activity was inversely related to glucose intolerance, obesity and central distribution of fat, particularly in males. Subjects with diabetes were currently less active and reported less historical physical activity than non-diabetic subjects. These findings suggest that activity may protect against the development of non-insulin-dependent diabetes both directly and through an influence on obesity and fat distribution.

Can physical activity mitigate the effects of aging in middle-aged women?

Background Aging is associated with an increased risk of women dying from coronary heart disease as well as from all causes combined. Alterations in the major biological risk factors for early coronary heart disease and all-cause mortality are frequently seen in aging. Methods and Results The present investigation tested the hypothesis that high levels of physical activity could protect against age-associated changes in biological risk factor levels. In the Healthy Women Study, 507 women were evaluated at study entry and 3 years later. Weekly physical activity level was measured at each examination via the Paffenbarger Physical Activity Questionnaire. During the 3-year period, women increased significantly in weight, blood pressure, levels of total and low-density lipoprotein cholesterol, triglycerides, and insulin and decreased significantly in levels of total high-density lipoprotein cholesterol (HDL-C) and HDL2-C. Conclusions Consistent with the study hypothesis, women who reported higher levels of activity at baseline had less weight gain over time. Furthermore, women who increased their activity during the 3-year interval had the smallest increases in weight and tended to have the smallest decreases in total HDL-C and HDL2-C. The changes in lipids due to activity were largely independent of changes in body weight.

Insulin-dependent diabetes mellitus mortality. The risk of cigarette smoking.

The relation between cigarette smoking and mortality was examined prospectively in a population of adult insulin-dependent diabetes mellitus (IDDM) patients. In 1981, information on smoking history and other health and lifestyle factors was obtained by questionnaire from 93% of the 723 patients included in the Childrens Hospital of Pittsburgh IDDM registry who were diagnosed between 1950 and 1964. Vital status as of January 1, 1988 was ascertained for 98% of the 548 patients who participated in the baseline survey and were alive as of January 1, 1982. Fifty-four cases died during the 6-year follow-up (32 male, 22 female). Proportional hazards analysis revealed that heavy smoking was a significant independent predictor of all-cause mortality among females but not males. The excess mortality in female diabetics was explained primarily by a marked excess risk of coronary heart disease mortality in smokers. These data strongly suggest that cigarette smoking, especially among diabetic females, should be avoided in order to improve longevity.

Sagittal diameter in comparison with single slice CT as a predictor of total visceral adipose tissue volume

BACKGROUND: Abdominal obesity has an important biological and epidemiological relationship to disease. The gold standard for measurement of visceral adipose tissue (VAT) is assessment by computerized tomography (CT) or magnetic resonance imaging (MRI), but because of simplicity and ease in collection, anthropometric variables are a desirable alternative to estimate VAT.OBJECTIVE: To compare the abilities of a single slice CT scan through the L4-L5 interspace (L4-L5 VAT), sagittal diameter, and body mass index (BMI) to estimate total volume VAT. Total volume VAT (the gold standard) was measured by total abdominal CT scanning, with a mean of 42 CT slices per patient. Estimation of VAT in subjects of similar body size was emphasized.DESIGN: Retrospective study of subjects undergoing complete abdominal and pelvic CT scanning for clinical reasons.SUBJECTS: 40 subjects (20 men and 20 women) mean age 56.5 y, with a balanced selection for BMI <27 and >27.RESULTS: In univariate regression models, L4-L5 VAT explained the largest proportion of the variance in total VAT (R2=0.87 (P<0.001)), though age (R2=0.11 (P=0.04)), BMI (R2=0.37 (P<0.001)), and sagittal diameter (R2=0.50 (P<0.001)) were also statistically significantly related to total VAT. When limited to individuals with a BMI≥27 however, L4-L5 VAT explained a large proportion of the variance in total VAT (R2=0.87 (P<0.001)) whereas sagittal diameter was only of borderline significance (R2=0.20 (P=0.06)), and BMI was not associated with total VAT (R2=0.04 (P=NS)). In multiple regression analyses, L4-L5 VAT area explained a large proportion of the variance (0.84–0.90), and once in the model, BMI, sagittal diameter, and age did not additionally contribute significantly to the explained variance in total VAT.CONCLUSIONS: Abdominal sagittal diameter is poorly correlated to total VAT for men and women with a BMI≥27. Within a 2 cm range of sagittal diameter, there is nearly a three-fold variability in total VAT.

CHOLECYSTECTOMY AND RIGHT-SIDED COLON CANCER: AN EPIDEMIOLOGICAL STUDY

The relation between prior cholecystectomy and right-sided colon cancer was investigated in a case-control study of 150 patients with histologically confirmed adenocarcinoma of the caecum or ascending colon and of two comparison groups. One comparison group consisted of 150 patients, matched for age, sex, and race, who had histologically confirmed adenocarcinoma of the descending or sigmoid colon and the other of 123 neighbourhood controls. Compared with left-sided cancer controls, the right-sided colon cancer cases had a relative risk of 1.87 for colon cancer after cholecystectomy. The relative risk was 1.86 when they were compared with the neighbourhood controls. When compared with both control groups relative risk was 1.77, with 95% confidence limits of 0.95 and 3.3 (p = 0.07). The increased risk of right-sided colon cancer after cholecystectomy may be associated with changes in biliary metabolism occurring after removal of a gall bladder.

HLA Heterogeneity of Insulin-dependent Diabetes Mellitus at Diagnosis: The Pittsburgh IDDM Study

Although some previous studies have suggested that insulin-dependent diabetes mellitus (IDDM) is a heterogeneous condition with variant forms being associated with HLA-DR types, the evidence, thus far, is conflicting. To address this issue, we have examined the presenting characteristics of a consecutive admission series of 200 newly diagnosed cases of IDDM from the Childrens Hospital of Pittsburgh. Because HLA-DR frequencies vary by race, data are presented only for the 172 white cases with complete HLA-DR typing. HLADR3 was found more frequently among male cases and DR4 among female cases (P < 0.005). Generally, patients with DR4 presented with a severer clinical picture, being more likely to have impaired consciousness and significant dehydration. In addition, patients with DR4 were more likely to be acidotic, ketotic, and to more frequently report a recent viral infection. This latter finding was supported by a greater frequency of antibodies to Coxsackie-B viruses in the DR4 cases at presentation. These results therefore suggest that there is considerable heterogeneity in IDDM, at least in presenting characteristics, according to HLA-DR type.

Estrogen metabolites and the risk of breast cancer in older women.

Background Women who metabolize a large proportion of their estrogen via the 16&agr; hydroxylation pathway could be at a higher risk of breast cancer. The objective of this study was to test the hypothesis that serum concentrations of 2-hydroxyestrone (2-OHE1) and 16&agr;-hydroxyestrone (16&agr;-OHE1), as well as their ratio, predict the risk of breast cancer in older women. Methods We performed a case-cohort study of 272 women with confirmed incident breast cancer and 291 controls chosen randomly from the cohort. Estrogen metabolites were measured in serum collected at the baseline examination and stored at −120°C. Incident breast cancers were confirmed by medical records and pathology reports during an average follow-up of 8.7 years. Results Mean concentrations of 2-OHE1 and 16&agr;-OHE1, adjusted for age and body mass index, were 3% to 4% higher in cases compared with controls: 2-OHE1 was 176 pg/mL and 169 pg/mL and 16&agr;-OHE1 was 233 pg/mL and 226 pg/mL in cases and controls, respectively. There was, however, no difference in the ratio of 2-OHE1 to 16&agr;-OHE1. The risk of breast cancer in women with the highest quartile of this ratio compared with those in the lowest quartile was 1.17 (95% confidence interval = 0.73–1.87). Conclusion The study results do not support the hypothesis that the ratio of 2-OHE1 to 16&agr;-OHE1 predicts breast cancer risk.