Tricia Li

Abdominal Obesity and the Risk of All-Cause, Cardiovascular, and Cancer Mortality Sixteen Years of Follow-Up in US Women

Background— Accumulating evidence indicates that abdominal adiposity is positively related to cardiovascular disease (CVD) risk and some other diseases independently of overall adiposity. However, the association of premature death resulting from these diseases with abdominal adiposity has not been widely studied, and findings are inconsistent. Methods and Results— In a prospective cohort study of 44 636 women in the Nurses’ Health Study, associations of abdominal adiposity with all-cause and cause-specific mortality were examined. During 16 years of follow-up, 3507 deaths were identified, including 751 cardiovascular deaths and 1748 cancer deaths. After adjustment for body mass index and potential confounders, the relative risks across the lowest to the highest waist circumference quintiles were 1.00, 1.11, 1.17, 1.31, and 1.79 (95% confidence interval [CI], 1.47 to 1.98) for all-cause mortality; 1.00, 1.04, 1.04, 1.28, and 1.99 (95% CI, 1.44 to 2.73) for CVD mortality; and 1.00, 1.18, 1.20, 1.34, and 1.63 (95% CI, 1.32 to 2.01) for cancer mortality (all P<0.001 for trend). Among normal-weight women (body mass index, 18.5 to <25 kg/m2), abdominal obesity was significantly associated with elevated CVD mortality: Relative risk associated with waist circumference ≥88 cm was 3.02 (95% CI, 1.31 to 6.99) and for waist-to-hip ratio >0.88 was 3.45 (95% CI, 2.02 to 6.92). After adjustment for waist circumference, hip circumference was significantly and inversely associated with CVD mortality. Conclusions— Anthropometric measures of abdominal adiposity were strongly and positively associated with all-cause, CVD, and cancer mortality independently of body mass index. Elevated waist circumference was associated with significantly increased CVD mortality even among normal-weight women.

Obesity as Compared With Physical Activity in Predicting Risk of Coronary Heart Disease in Women

Background— The comparative importance of physical inactivity and obesity as predictors of coronary heart disease (CHD) risk remains unsettled. Methods and Results— We followed 88 393 women, 34 to 59 years of age, in the Nurses’ Health Study from 1980 to 2000. These participants did not have cardiovascular disease and cancer at baseline. We documented 2358 incident major CHD events (including nonfatal myocardial infarction and fatal CHD) during 20 years of follow-up, including 889 cases of fatal CHD and 1469 cases of nonfatal myocardial infarction. In a multivariate model adjusting for cardiovascular risk factors, overweight and obesity were significantly associated with increased risk of CHD, whereas increasing levels of physical activity were associated with a graded reduction in CHD risk (P<0.001). In joint analyses of body mass index (BMI) and physical activity in women who had a healthy weight (BMI, 18.5 to 24.9 kg/m2) and were physically active (exercise ≥3.5 h/wk) as the reference group, the relative risks of CHD were 3.44 (95% confidence interval [CI], 2.81 to 4.21) for women who were obese (BMI ≥30 kg/m2) and sedentary (exercise <1 h/wk), 2.48 (95% CI, 1.84 to 3.34) for women who were active but obese, and 1.48 (95% CI, 1.24 to 1.77) for women who had a healthy weight but were sedentary. In combined analyses of waist-hip ratio and physical activity, both waist-hip ratio and physical activity were significant predictors of CHD, and the highest risk was among women in the lowest category of physical activity and the highest tertile of waist-hip ratio (relative risk=3.03; 95% CI, 1.96 to 4.18). Even a modest weight gain (4 to 10 kg) during adulthood was associated with 27% (95% CI, 12% to 45%) increased risk of CHD compared with women with a stable weight after adjusting for physical activity and other cardiovascular risk factors. Conclusions— Obesity and physical inactivity independently contribute to the development of CHD in women. These data underscore the importance of both maintaining a healthy weight and regular physical activity in preventing CHD.

Combined impact of lifestyle factors on mortality: prospective cohort study in US women

Objective To evaluate the impact of combinations of lifestyle factors on mortality in middle aged women. Design Prospective cohort study. Setting Nurses’ health study, United States. Participants 77 782 women aged 34 to 59 years and free from cardiovascular disease and cancer in 1980. Main outcome measure Relative risk of mortality during 24 years of follow-up in relation to five lifestyle factors (cigarette smoking, being overweight, taking little moderate to vigorous physical activity, no light to moderate alcohol intake, and low diet quality score). Results 8882 deaths were documented, including 1790 from cardiovascular disease and 4527 from cancer. Each lifestyle factor independently and significantly predicted mortality. Relative risks for five compared with zero lifestyle risk factors were 3.26 (95% confidence interval 2.45 to 4.34) for cancer mortality, 8.17 (4.96 to 13.47) for cardiovascular mortality, and 4.31 (3.51 to 5.31) for all cause mortality. A total of 28% (25% to 31%) of deaths during follow-up could be attributed to smoking and 55% (47% to 62%) to the combination of smoking, being overweight, lack of physical activity, and a low diet quality. Additionally considering alcohol intake did not substantially change this estimate. Conclusions These results indicate that adherence to lifestyle guidelines is associated with markedly lower mortality in middle aged women. Both efforts to eradicate cigarette smoking and those to stimulate regular physical activity and a healthy diet should be intensified.

Intake of Fruit, Vegetables, and Fruit Juices and Risk of Diabetes in Women

OBJECTIVE—The purpose of this study was to examine the association between fruit, vegetable, and fruit juice intake and development of type 2 diabetes. RESEARCH DESIGN AND METHODS—A total of 71,346 female nurses aged 38–63 years who were free of cardiovascular disease, cancer, and diabetes in 1984 were followed for 18 years, and dietary information was collected using a semiquantitative food frequency questionnaire every 4 years. Diagnosis of diabetes was self-reported. RESULTS—During follow-up, 4,529 cases of diabetes were documented, and the cumulative incidence of diabetes was 7.4%. An increase of three servings/day in total fruit and vegetable consumption was not associated with development of diabetes (multivariate-adjusted hazard ratio 0.99 [95% CI 0.94–1.05]), whereas the same increase in whole fruit consumption was associated with a lower hazard of diabetes (0.82 [0.72–0.94]). An increase of 1 serving/day in green leafy vegetable consumption was associated with a modestly lower hazard of diabetes (0.91 [0.84–0.98]), whereas the same change in fruit juice intake was associated with an increased hazard of diabetes (1.18 [1.10–1.26]). CONCLUSIONS—Consumption of green leafy vegetables and fruit was associated with a lower hazard of diabetes, whereas consumption of fruit juices may be associated with an increased hazard among women.

Regular Consumption of Nuts Is Associated with a Lower Risk of Cardiovascular Disease in Women with Type 2 Diabetes

Higher nut consumption has been associated with lower risk of coronary heart disease (CHD) events in several epidemiologic studies. The study examined the association between intake of nuts and incident cardiovascular disease (CVD) in a cohort of women with type 2 diabetes. For the primary analysis, there were 6309 women with type 2 diabetes who completed a validated FFQ every 2-4 y between 1980 and 2002 and were without CVD or cancer at study entry. Major CVD events included incident myocardial infarction (MI), revascularization, and stroke. During 54,656 person-years of follow-up, there were 452 CHD events (including MI and revascularization) and 182 incident stroke cases. Frequent nut and peanut butter consumption was inversely associated with total CVD risk in age-adjusted analyses. After adjustment for conventional CVD risk factors, consumption of at least 5 servings/wk of nuts or peanut butter [serving size, 28 g (1 ounce) for nuts and 16 g (1 tablespoon) for peanut butter] was significantly associated with a lower risk of CVD (relative risk = 0.56; 95% CI: 0.36-0.89). Furthermore, when we evaluated plasma lipid and inflammatory biomarkers, we observed that increasing nut consumption was significantly associated with a more favorable plasma lipid profile, including lower LDL cholesterol, non-HDL cholesterol, total cholesterol, and apolipoprotein-B-100 concentrations. However, we did not observe significant associations for HDL cholesterol or inflammatory markers. These data suggest that frequent nut and peanut butter consumption is associated with a significantly lower CVD risk in women with type 2 diabetes.

PROSPECTIVE STUDY OF TYPE 1 AND TYPE 2 DIABETES AND RISK OF STROKE SUBTYPES: THE NURSES' HEALTH STUDY

OBJECTIVE— The aim of this study was to examine the relationship between type 1 and type 2 diabetes and risk of stroke subtypes in women. RESEARCH DESIGN AND METHODS— We followed 116,316 women aged 30–55 years in 1976 through 2002 for incidence of stroke. At baseline and through biennial follow-up, women were asked about their history and treatment of diabetes and other potential risk factors for stroke. RESULTS— During 2.87 million person-years of follow-up, 3,463 incident strokes occurred. In multivariate analyses, the incidence of total stroke was fourfold higher in women with type 1 diabetes (relative risk [RR] 4.7 [95% CI 3.3–6.6]) and twofold higher among women with type 2 diabetes (1.8 [1.7–2.0]) than for nondiabetic women. The multivariate RR of ischemic stroke was increased sixfold (6.3 [4.0–9.8]) in type 1 diabetes and twofold (2.3 [2.0–2.6]) in type 2 diabetes. Risks for large-artery infarction and lacunar stroke were similar. Type 1 diabetes was also significantly associated with the risk of hemorrhagic stroke (3.8 [1.2–11.8]), but type 2 diabetes was not (1.0 [0.7–1.4]). CONCLUSIONS— Both type 1 and type 2 diabetes are associated with substantially increased risks of total and most subtypes of stroke.

Separating the Mechanism-Based and Off-Target Actions of Cholesteryl Ester Transfer Protein Inhibitors With CETP Gene Polymorphisms

Background— Cholesteryl ester transfer protein (CETP) inhibitors raise high-density lipoprotein (HDL) cholesterol, but torcetrapib, the first-in-class inhibitor tested in a large outcome trial, caused an unexpected blood pressure elevation and increased cardiovascular events. Whether the hypertensive effect resulted from CETP inhibition or an off-target action of torcetrapib has been debated. We hypothesized that common single-nucleotide polymorphisms in the CETP gene could help distinguish mechanism-based from off-target actions of CETP inhibitors to inform on the validity of CETP as a therapeutic target. Methods and Results— We compared the effect of CETP single-nucleotide polymorphisms and torcetrapib treatment on lipid fractions, blood pressure, and electrolytes in up to 67 687 individuals from genetic studies and 17 911 from randomized trials. CETP single-nucleotide polymorphisms and torcetrapib treatment reduced CETP activity and had a directionally concordant effect on 8 lipid and lipoprotein traits (total, low-density lipoprotein, and HDL cholesterol; HDL2; HDL3; apolipoproteins A-I and B; and triglycerides), with the genetic effect on HDL cholesterol (0.13 mmol/L, 95% confidence interval [CI] 0.11 to 0.14 mmol/L) being consistent with that expected of a 10-mg dose of torcetrapib (0.13 mmol/L, 95% CI 0.10 to 0.15). In trials, 60 mg of torcetrapib elevated systolic and diastolic blood pressure by 4.47 mm Hg (95% CI 4.10 to 4.84 mm Hg) and 2.08 mm Hg (95% CI 1.84 to 2.31 mm Hg), respectively. However, the effect of CETP single-nucleotide polymorphisms on systolic blood pressure (0.16 mm Hg, 95% CI −0.28 to 0.60 mm Hg) and diastolic blood pressure (−0.04 mm Hg, 95% CI −0.36 to 0.28 mm Hg) was null and significantly different from that expected of 10 mg of torcetrapib. Conclusions— Discordance in the effects of CETP single-nucleotide polymorphisms and torcetrapib treatment on blood pressure despite the concordant effects on lipids indicates the hypertensive action of torcetrapib is unlikely to be due to CETP inhibition or shared by chemically dissimilar CETP inhibitors. Genetic studies could find a place in drug-development programs as a new source of randomized evidence for drug-target validation in humans.

Smoking and risk of skin cancer: a prospective analysis and a meta-analysis

BACKGROUND The association between smoking and the risk of skin cancer has not been well established. METHODS In two large cohorts in the USA, we prospectively examined the risks of melanoma, basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) among participants grouped according to smoking variables. RESULTS Among men, compared with never smokers, ever smokers had a significantly lower risk of melanoma [relative risk (RR) = 0.72; 95% confidence interval (CI): 0.58-0.86]; those who smoked for ≥30 years had an RR of 0.65 (95% CI: 0.48-0.89) (P(trend) = 0.003); those who smoked ≥15 cigarettes per day had an RR of 0.32 (95% CI: 0.13-0.78) (P(trend) = 0.006) and those who smoked for > 45 pack years had an RR of 0.66 (95% CI: 0.45-0.97) (P(trend) = 0.03). Ever smokers also had a slightly lower risk of BCC (RR = 0.94; 95% CI: 0.90-0.98). There was no significant association for SCC (RR = 0.99; 95% CI: 0.89-1.12). In women, no significant association was found for melanoma (RR = 0.96; 95% CI: 0.83-1.10). Compared with never smokers, ever smokers had a slightly higher risk of BCC (RR = 1.06; 95% CI: 1.03-1.08) and a higher risk of SCC (RR = 1.19; 95% CI: 1.08-1.31). A significant inverse association between smoking and melanoma was limited to the head and neck (RR = 0.65; 95% CI: 0.42-0.89). CONCLUSIONS Smoking was inversely associated with melanoma risk, especially on the head and neck. Further studies are warranted to investigate the underlying mechanism(s).

Obesity, waist circumference, weight change and the risk of psoriasis in US women

Objective  To evaluate the associations between body mass index (BMI), weight change, waist circumference, hip circumference and risk of incident psoriasis.

Coffee Consumption and Risk of Cardiovascular Diseases and All-Cause Mortality Among Men With Type 2 Diabetes

OBJECTIVE Coffee consumption has been linked to detrimental acute metabolic and hemodynamic effects. We investigated coffee consumption in relation to risk of CVDs and mortality in diabetic men. RESEARCH DESIGN AND METHODS We conducted a prospective cohort study including 3,497 diabetic men without CVD at baseline. RESULTS After adjustment for age, smoking, and other cardiovascular risk factors, relative risks (RRs) were 0.88 (95% CI 0.50–1.57) for CVDs (P for trend = 0.29) and 0.80 (0.41–1.54) for all-cause mortality (P for trend = 0.45) for the consumption of ≥4 cups/day of caffeinated coffee compared with those for non–coffee drinkers. Stratification by smoking and duration of diabetes yielded similar results. RRs for caffeine intake for the highest compared with the lowest quintile were 1.02 (0.70–1.47; P for trend = 0.96) for CVDs and 0.96 (0.64–1.44; P for trend = 0.69) for mortality. CONCLUSIONS These data indicate that regular coffee consumption is not associated with increased risk for CVDs or mortality in diabetic men.