Howard D. Sesso

Body-mass index and mortality among 1.46 million white adults.

BACKGROUND A high body-mass index (BMI, the weight in kilograms divided by the square of the height in meters) is associated with increased mortality from cardiovascular disease and certain cancers, but the precise relationship between BMI and all-cause mortality remains uncertain. METHODS We used Cox regression to estimate hazard ratios and 95% confidence intervals for an association between BMI and all-cause mortality, adjusting for age, study, physical activity, alcohol consumption, education, and marital status in pooled data from 19 prospective studies encompassing 1.46 million white adults, 19 to 84 years of age (median, 58). RESULTS The median baseline BMI was 26.2. During a median follow-up period of 10 years (range, 5 to 28), 160,087 deaths were identified. Among healthy participants who never smoked, there was a J-shaped relationship between BMI and all-cause mortality. With a BMI of 22.5 to 24.9 as the reference category, hazard ratios among women were 1.47 (95 percent confidence interval [CI], 1.33 to 1.62) for a BMI of 15.0 to 18.4; 1.14 (95% CI, 1.07 to 1.22) for a BMI of 18.5 to 19.9; 1.00 (95% CI, 0.96 to 1.04) for a BMI of 20.0 to 22.4; 1.13 (95% CI, 1.09 to 1.17) for a BMI of 25.0 to 29.9; 1.44 (95% CI, 1.38 to 1.50) for a BMI of 30.0 to 34.9; 1.88 (95% CI, 1.77 to 2.00) for a BMI of 35.0 to 39.9; and 2.51 (95% CI, 2.30 to 2.73) for a BMI of 40.0 to 49.9. In general, the hazard ratios for the men were similar. Hazard ratios for a BMI below 20.0 were attenuated with longer-term follow-up. CONCLUSIONS In white adults, overweight and obesity (and possibly underweight) are associated with increased all-cause mortality. All-cause mortality is generally lowest with a BMI of 20.0 to 24.9.

Physical Activity and Coronary Heart Disease in Men The Harvard Alumni Health Study

BackgroundThe quantity and intensity of physical activity required for the primary prevention of coronary heart disease (CHD) remain unclear. Therefore, we examined the association of the quantity and intensity of physical activity with CHD risk and the impact of other coronary risk factors. Methods and ResultsWe followed 12 516 middle-aged and older men (mean age 57.7 years, range 39 to 88 years) from 1977 through 1993. Physical activity was assessed at baseline in kilojoules per week (4.2 kJ=1 kcal) from blocks walked, flights climbed, and participation in sports or recreational activities. During follow-up, 2135 cases of incident CHD, including myocardial infarction, angina pectoris, revascularization, and coronary death, occurred. Compared with men expending <2100 kJ/wk, men expending 2100 to 4199, 4200 to 8399, 8400 to 12 599, and ≥12 600 kJ/wk had multivariate relative risks of 0.90, 0.81, 0.80, and 0.81, respectively (P for trend=0.003). When we considered the independent effects of specific physical activity components, only total sports or recreational activities (P for trend=0.042) and vigorous activities (P for trend=0.02) were inversely associated with the risk of CHD. These associations did not differ within subgroups of men defined by coronary risk factors. Finally, among men with multiple coronary risk factors, those expending ≥4200 kJ/wk had reduced CHD risk compared with men expending <4200 kJ/wk. ConclusionsTotal physical activity and vigorous activities showed the strongest reductions in CHD risk. Moderate and light activities, which may be less precisely measured, showed nonsignificant inverse associations. The association between physical activity and a reduced risk of CHD also extends to men with multiple coronary risk factors.

Systematic Review: Vitamin D and Calcium Supplementation in Prevention of Cardiovascular Events

BACKGROUND Vitamin D and calcium may affect the cardiovascular system independently and interactively. PURPOSE To assess whether vitamin D and calcium supplements reduce the risk for cardiovascular events in adults. DATA SOURCES Studies published in English from 1966 to July 2009 in MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials. STUDY SELECTION Two investigators independently selected 17 prospective studies and randomized trials that examined vitamin D supplementation, calcium supplementation, or both and subsequent cardiovascular events. DATA EXTRACTION Three investigators extracted and checked data about study designs, participants, exposures or interventions, outcomes, and data quality. DATA SYNTHESIS Five prospective studies of patients receiving dialysis and 1 study involving a general population showed consistent reductions in cardiovascular disease (CVD) mortality among adults who received vitamin D supplements. Four prospective studies of initially healthy persons found no differences in incidence of CVD between calcium supplement recipients and nonrecipients. Results of secondary analyses in 8 randomized trials showed a slight but statistically nonsignificant reduction in CVD risk (pooled relative risk, 0.90 [95% CI, 0.77 to 1.05]) with vitamin D supplementation at moderate to high doses (approximately 1000 IU/d) but not with calcium supplementation (pooled relative risk, 1.14 [CI, 0.92 to 1.41]), or a combination of vitamin D and calcium supplementation (pooled relative risk, 1.04 [CI, 0.92 to 1.18]) compared with placebo. LIMITATIONS Only articles published in English that reported cardiovascular event outcomes were included. The small number of studies, the lack of trials designed specifically to assess primary effects on cardiovascular outcomes, and important between-study heterogeneity preclude definitive conclusions. CONCLUSION Evidence from limited data suggests that vitamin D supplements at moderate to high doses may reduce CVD risk, whereas calcium supplements seem to have minimal cardiovascular effects. Further research is needed to elucidate the role of these supplements in CVD prevention. PRIMARY FUNDING SOURCE The American Heart Association and the National Heart, Lung, and Blood Institute.

Circulating 25-Hydroxy-Vitamin D and Risk of Cardiovascular Disease A Meta-Analysis of Prospective Studies

Background—Vitamin D status has been linked to the risk of cardiovascular disease (CVD). However, the optimal 25-hydroxy-vitamin D (25[OH]-vitamin D) levels for potential cardiovascular health benefits remain unclear. Methods and Results—We searched MEDLINE and EMBASE from 1966 through February 2012 for prospective studies that assessed the association of 25(OH)-vitamin D concentrations with CVD risk. A total of 24 articles met our inclusion criteria, from which 19 independent studies with 6123 CVD cases in 65 994 participants were included for a meta-analysis. In a comparison of the lowest with the highest 25(OH)-vitamin D categories, the pooled relative risk was 1.52 (95% confidence interval, 1.30–1.77) for total CVD, 1.42 (95% confidence interval, 1.19–1.71) for CVD mortality, 1.38 (95% confidence interval, 1.21–1.57) for coronary heart disease, and 1.64 (95% confidence interval, 1.27–2.10) for stroke. These associations remained strong and significant when analyses were limited to studies that excluded participants with baseline CVD and were better controlled for season and confounding. We used a fractional polynomial spline regression analysis to assess the linearity of dose–response association between continuous 25(OH)-vitamin D and CVD risk. The CVD risk increased monotonically across decreasing 25(OH)-vitamin D below ≈60 nmol/L, with a relative risk of 1.03 (95% confidence interval, 1.00–1.06) per 25-nmol/L decrement in 25(OH)-vitamin D. Conclusions—This meta-analysis demonstrated a generally linear, inverse association between circulating 25(OH)-vitamin D ranging from 20 to 60 nmol/L and risk of CVD. Further research is needed to clarify the association of 25(OH)-vitamin D higher than 60 nmol/L with CVD risk and assess causality of the observed associations.

Systolic and Diastolic Blood Pressure, Pulse Pressure, and Mean Arterial Pressure as Predictors of Cardiovascular Disease Risk in Men

We compared systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure (PP), and mean arterial pressure (MAP) in predicting the risk of cardiovascular disease (CVD), stratifying results at age 60 years, when DBP decreases while SBP continues to increase. We prospectively followed 11 150 male physicians with no history of CVD or antihypertensive treatment through the 2-year questionnaire, after which follow-up began. Reported blood pressure was averaged from both the baseline and 2-year questionnaires. During a median follow-up of 10.8 years, there were 905 cases of incident CVD. For men aged <60 years (n=8743), those in the highest versus lowest quartiles of average SBP (≥130 versus <116 mm Hg), DBP (≥81 versus <73 mm Hg), and MAP (≥97 versus <88 mm Hg) had relative risks (RRs) of CVD of 2.16, 2.23, and 2.52, respectively. Models with average MAP and PP did not add information compared with models with MAP alone (P >0.05). For men aged ≥60 years (n=2407), those in the highest versus lowest quartiles of average SBP (≥135 versus <120 mm Hg), PP (≥55 versus <44 mm Hg), and MAP (≥99 versus <91 mm Hg) had RRs of CVD of 1.69, 1.83, and 1.43, respectively. The addition of other blood pressure measures did not add information compared with average SBP or PP alone (all P >0.05). These data suggest that average SBP, DBP, and MAP strongly predict CVD among younger men, whereas either average SBP or PP predicts CVD among older men. More research should distinguish whether MAP, highly correlated with SBP and DBP, better predicts CVD.

Relative Intensity of Physical Activity and Risk of Coronary Heart Disease

Background—Current recommendations prescribe at least moderate-intensity physical activity, requiring ≥3 METs (metabolic equivalents) for ≥30 minutes almost daily, generating ≈1000 kcal/wk. Defining intensity using an absolute scale in METs may be limited because it neglects variations in physical fitness: an activity requiring a particular MET value commands greater physical effort among less fit than more fit persons. It is unknown whether moderate-intensity exercise, relative to an individual’s capacity, is associated with reduced coronary heart disease (CHD) rates. Methods and Results—We followed 7337 men (mean age, 66 years) from 1988 to 1995. At baseline, men reported their actual activities and, using the Borg Scale, the perceived level of exertion when exercising (relative intensity). During follow-up, 551 men developed CHD. After multivariate adjustment, the relative risks of CHD among men who perceived their exercise exertion as “moderate,” “somewhat strong,” and “strong” or more intense were 0.86 (95% confidence interval, 0.66 to 1.13), 0.69 (0.51 to 0.94), and 0.72 (0.52 to 1.00), respectively (Ptrend=0.02), compared with “weak” or less intense. This inverse association extended to men not fulfilling current recommendations, ie, expending <1000 kcal/wk in physical activity or not engaging in activities of ≥3 METs (Ptrend=0.03 and 0.007, respectively). Conclusions—There is an inverse association between relative intensity of physical activity (an individual’s perceived level of exertion) and risk of CHD, even among men not satisfying current activity recommendations. Recommendations for “moderate”-intensity physical activity may need to consider individual fitness levels instead of globally prescribing activities of ≥3 METs.

Dietary Intake of Dairy Products, Calcium, and Vitamin D and the Risk of Hypertension in Middle-Aged and Older Women

Prospective data on the associations between intake of dairy products and its nutrient components with risk of hypertension remain limited. We therefore investigated the associations of intake of dairy products, calcium, and vitamin D with the incidence of hypertension in a prospective cohort of 28 886 US women aged ≥45 years. Intake of dairy products, calcium, and vitamin D at baseline were assessed from semiquantitative food frequency questionnaires. Incident cases of hypertension (n=8710) were identified from annual follow-up questionnaires during 10 years of follow-up. After adjusting for major hypertension risk factors, the relative risks of incident hypertension across increasing quintiles of low-fat dairy product intake were 1.00 (reference), 0.98, 0.97, 0.95, and 0.89 (P for trend: 0.001). The risk of hypertension decreased in the higher quintiles of dietary calcium (multivariate relative risk in the highest quintile: 0.87) and dietary vitamin D (multivariate relative risk in the highest quintile: 0.95), but did not change with calcium or vitamin D supplements. Adjustment for dietary calcium significantly attenuated the inverse association of low-fat dairy intake with risk of hypertension, whereas adjustment for dietary vitamin D did not change the association. The multivariate relative risks across increasing quintiles of high-fat dairy product intake, in contrast, were 1.00, 1.02, 1.01, 1.00, and 0.97 (P for trend: 0.17). Our study found that intakes of low-fat dairy products, calcium, and vitamin D were each inversely associated with risk of hypertension in middle-aged and older women, suggesting their potential roles in the primary prevention of hypertension and cardiovascular complications.

Associations of dietary flavonoids with risk of type 2 diabetes, and markers of insulin resistance and systemic inflammation in women: a prospective study and cross-sectional analysis.

Objective: Flavonoids, as antioxidants, may prevent the progressive impairment of pancreatic β-cell function due to oxidative stress and may thus reduce the occurrence of type 2 diabetes. The aim of the present study was to examine the association of dietary flavonol and flavone intake with type 2 diabetes, and biomarkers of insulin resistance and systemic inflammation. Methods: In 38,018 women aged ≥45 y and free of cardiovascular disease, cancer and diabetes with an average 8.8y of follow-up, we calculated relative risks (RRs) of incident type 2 diabetes (1,614 events) according to dietary intake of total or individual flavonols and flavones and flavonoid-rich foods. We also measured and examined plasma concentrations of insulin, HbA1C, CRP, and IL-6 in relation to total flavonol and flavone intake among 344 nondiabetic women. Results: During 332,905 person-years of follow-up, none of total flavonols and flavones, quercetin, kaempferol, myricetin, apigenin, and luteolin was significantly associated with risk of type 2 diabetes. Among flavonoid-rich foods, apple and tea consumption was associated with diabetes risk. Women consuming ≥1 apple/d showed a significant 28% reduced risk of type 2 diabetes compared with those who consumed no apples (the multivariate-adjusted RR = 0.72, 95% CI: 0.56, 0.92; p = 0.006 for trend). Tea consumption was also inversely associated with diabetes risk but with a borderline significant trend (≥4 cups/d vs. none: RR 0.73, 95% CI: 0.52–1.01; p for trend = 0.06). In 344 nondiabetic women, total intake of flavonols and flavones was not significantly related to plasma concentrations of fasting insulin, HbA1C, CRP, or IL-6. Conclusions: These results do not support the hypothesis that high intake of flavonols and flavones reduces the development of type 2 diabetes, although we cannot rule out a modest inverse association with intake of apples and tea.

Alcohol Consumption and the Risk of Hypertension in Women and Men

Heavy alcohol intake increases the risk of hypertension, but the relationship between light-to-moderate alcohol consumption and incident hypertension remains controversial. We prospectively followed 28 848 women from the Women’s Health Study and 13 455 men from the Physicians’ Health Study free of baseline hypertension, cardiovascular disease, and cancer. Self-reported lifestyle and clinical risk factors were collected. In women, total alcohol intake was summed from liquor, red wine, white wine, and beer; men reported total alcohol intake from a single combined question. During 10.9 and 21.8 years of follow-up, 8680 women and 6012 men developed hypertension (defined as new physician diagnosis, antihypertensive treatment, reported systolic blood pressure ≥140 mm Hg, or diastolic blood pressure ≥90 mm Hg). In women, we found a J-shaped association between alcohol intake and hypertension in age- and lifestyle-adjusted models. Adding potential intermediates (body mass index, diabetes, and high cholesterol) attenuated the benefits of alcohol in the light-to-moderate range and strengthened the adverse effects of heavy alcohol intake. Beverage-specific relative risks paralleled those for total alcohol intake. In men, alcohol intake was positively and significantly associated with the risk of hypertension and persisted after multivariate adjustment. Models stratified by baseline systolic blood pressure (<120 versus ≥120 mm Hg) or diastolic blood pressure (<75 versus ≥75 mm Hg) did not alter the relative risks in women and men. In conclusion, light-to-moderate alcohol consumption decreased hypertension risk in women and increased risk in men. The threshold above which alcohol became deleterious for hypertension risk emerged at ≥4 drinks per day in women versus a moderate level of ≥1 drink per day in men.

Physical Activity and Coronary Heart Disease Risk in Men Does the Duration of Exercise Episodes Predict Risk

BackgroundPhysical activity is associated with a decreased risk of coronary heart disease (CHD). However, it is unclear whether the duration of exercise episodes is important: Are accumulated shorter sessions as predictive of decreased risk as longer sessions if the same amount of energy is expended? Methods and ResultsIn the Harvard Alumni Health Study, we prospectively followed 7307 Harvard University alumni (mean age 66.1 years) from 1988 through 1993. At baseline, men reported their walking, stair climbing, and participation in sports or recreational activities. For each of the latter activities, they also reported the frequency and average duration per episode. During follow-up, 482 men developed CHD. In age-adjusted analysis, a longer duration of exercise episodes predicted lower CHD risk (P trend=0.04). However, after total energy expended on physical activity and potential confounders was accounted for, duration no longer had an independent effect on CHD risk (P trend=0.25); that is, longer sessions of exercise did not have a different effect on risk compared with shorter sessions, as long as the total energy expended was similar. In contrast, higher levels of total energy expenditure significantly predicted decreased CHD risk in both age-adjusted (P trend=0.009) and multivariate (P trend=0.046) analyses. ConclusionsThese data clearly indicate that physical activity is associated with decreased CHD risk. Furthermore, they lend some support to recent recommendations that allow for the accumulation of shorter sessions of physical activity, as opposed to requiring 1 longer, continuous session of exercise. This may provide some impetus for those sedentary to become more active.