Flavonoid intake and the risk of cardiovascular disease in women

BACKGROUND: Despite emerging evidence of the role of flavonoids in cardiovascular disease (CVD) prevention, the association remains unclear. OBJECTIVE: We examined whether flavonoids and selected flavonols and flavones or their food sources are associated with CVD risk. DESIGN: Women (n = 38 445) free of CVD and cancer participated in a prospective study with a mean follow-up of 6.9 y. On the basis of a food-frequency questionnaire, total flavonoids and selected flavonols and flavones were categorized into quintiles, and food sources were categorized into 4 groups. Relative risks were computed for important vascular events (519 events; excluding revascularizations) and CVD (729 events), including myocardial infarction, stroke, revascularization, and CVD death. RESULTS: The mean flavonoid intake was 24.6 +/- 18.5 mg/d, primarily as quercetin (70.2%). For both CVD and important vascular events, no significant linear trend was observed across quintiles of flavonoid intake (P = 0.63 and 0.80, respectively). No individual flavonol or flavone was associated with CVD. Broccoli and apple consumption were associated with nonsignificant reductions in CVD risk: 25-30% and 13-22%, respectively. A small proportion of women (n = 1185) consuming > or =4 cups (946 mL) tea/d had a reduction in the risk of important vascular events but with a nonsignificant linear trend (P = 0.07). CONCLUSIONS: Flavonoid intake was not strongly associated with a reduced risk of CVD. The nonsignificant inverse associations for broccoli, apples, and tea with CVD were not mediated by flavonoids and warrant further study.     

Associations of dietary protein with disease and mortality in a prospective study of postmenopausal women

Some weight loss diets promote protein intake; however, the association of protein with disease is unclear. In 1986, 29,017 postmenopausal Iowa women without cancer, coronary heart disease (CHD), or diabetes were followed prospectively for 15 years for cancer incidence and mortality from CHD, cancer, and all causes. Mailed questionnaires assessed dietary, lifestyle, and medical information. Nutrient density models estimated risk ratios from a simulated substitution of total and type of dietary protein for carbohydrate and of vegetable for animal protein. The authors identified 4,843 new cancers, 739 CHD deaths, 1,676 cancer deaths, and 3,978 total deaths. Among women in the highest intake quintile, CHD mortality decreased by 30% from an isoenergetic substitution of vegetable protein for carbohydrate (95% confidence interval (CI): 0.49, 0.99) and of vegetable for animal protein (95% CI: 0.51, 0.98), following multivariable adjustment. Although no association was observed with any outcome when animal protein was substituted for carbohydrate, CHD mortality was associated with red meats (risk ratio = 1.44, 95% CI: 1.06, 1.94) and dairy products (risk ratio = 1.41, 95% CI: 1.07, 1.86) when substituted for servings per 1,000 kcal (4.2 MJ) of carbohydrate foods. Long-term adherence to high-protein diets, without discrimination toward protein source, may have potentially adverse health consequences.     

Dietary flavonoid intake and risk of cardiovascular disease in postmenopausal women.

Flavonoids, a group of phenolic compounds found in fruits and vegetables, are known to have antioxidant properties. They prevent low density lipoprotein oxidation in vitro and thus may play a role in the prevention of coronary heart disease (CHD). In 1986, in a prospective study of 34,492 postmenopausal women in Iowa, the authors examined the association of flavonoid intake with CHD and stroke mortality. Over 10 years of follow-up, 438 deaths from CHD and 131 deaths from stroke were documented. Total flavonoid intake was associated with a decreased risk of CHD death after adjusting for age and energy intake (p for trend = 0.04). This association was attenuated after multivariate adjustment. However, decreased risk was seen in each category of intake compared with the lowest. Relative risks and 95% confidence intervals of CHD death from lowest to highest intake category were 1.0, 0.67 (95% confidence interval (CI) 0.49-0.92), 0.56 (95% CI 0.39-0.79), 0.86 (95% CI 0.63-1.18), and 0.62 (95% CI 0.44-0.87).There was no association between total flavonoid intake and stroke mortality (p for trend = 0.83). Of the foods that contributed the most to flavonoid intake in this cohort, only broccoli was strongly associated with reduced risk of CHD death. The data of this study suggest that flavonoid intake may reduce risk of death from CHD in postmenopausal women.     

Non-participation and mortality in a prospective study of cardiovascular disease.

Men who did not participate in a prospective study of cardiovascular disease (The British Regional Heart Study) were younger than the participants, more likely to be unmarried, and more likely to be less skilled workers. In the first three years of follow-up, their total mortality rate was significantly higher than that of the participants; thereafter it declined to levels not significantly different from those of the participants. This excess of early deaths could not be attributed to age. There was a small but non significant excess mortality in non-participants due to neoplasms and cardiovascular disease and a somewhat greater excess from all other causes combined. The social characteristics of the non-participant population appear to contribute to their significantly higher total mortality rate, and allowance needs to be made for this in interpreting the study findings. However the death rate from cardiovascular disease was similar in participants and non-participants, suggesting that any analysis related to this particular cause of death should not be biased by non-participation.     

Dietary patterns and cardiovascular disease mortality in Japan: a prospective cohort study

BACKGROUND: Although ecological observations suggest that the Japanese diet may reduce the risk of cardiovascular disease (CVD), the impact of a Japanese dietary pattern upon mortality due to CVD is unclear. METHODS: We prospectively assessed the association between dietary patterns among the Japanese and CVD mortality. Dietary information was collected from 40 547 Japanese men and women aged 40-79 years without a history of diabetes, stroke, myocardial infarction or cancer at the baseline in 1994. RESULTS: During 7 years of follow-up, 801 participants died of CVD. Factor analysis (principal component) based on a validated food frequency questionnaire identified three dietary patterns: (i) a Japanese dietary pattern highly correlated with soybean products, fish, seaweeds, vegetables, fruits and green tea, (ii) an 'animal food' dietary pattern and (iii) a high-dairy, high-fruit-and-vegetable, low-alcohol (DFA) dietary pattern. The Japanese dietary pattern was related to high sodium intake and high prevalence of hypertension. After adjustment for potential confounders, the Japanese dietary pattern score was associated with a lower risk of CVD mortality (hazard ratio of the highest quartile vs the lowest, 0.73; 95% confidence interval: 0.59-0.90; P for trend = 0.003). The 'animal food' dietary pattern was associated with an increased risk of CVD, but the DFA dietary pattern was not. CONCLUSION: The Japanese dietary pattern was associated with a decreased risk of CVD mortality, despite its relation to sodium intake and hypertension.     

Methylenetetrahydrofolate reductase 677 C/T genotype and cardiovascular disease mortality in postmenopausal women

Methylenetetrahydrofolate reductase (MTHFR) is involved in the reduction of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate. A 677 C/T single nucleotide polymorphism localized in the MTHFR gene is associated with both thermolability and reduced activity of the enzyme and is associated with increased homocysteine levels. The authors investigated the relation between the MTHFR 677 C/T polymorphism and risk of cardiovascular disease mortality in a cohort study of 12,239 women initially aged 52--67 years with a maximum follow-up time of 18 years (1976--1995; 153,732 woman-years of follow-up). The cardiovascular disease mortality rate was highest among women with the MTHFR 677 CC wild-type genotype and lowest among MTHFR 677 TT homozygotes. In comparison with women with the 677 CC wild-type genotype, age-adjusted rate ratios were 0.7 (95% confidence interval: 0.5, 0.9) for 677 CT heterozygotes and 0.6 (95% confidence interval: 0.4, 1.0) for 677 TT homozygotes. The possibility that this relation is a chance finding must be considered, because the relation is weak and of borderline significance. However, it provides an important argument against the view that increased levels of homocysteine directly raise cardiovascular disease risk.     

Endogenous estrogen exposure and cardiovascular mortality risk in postmenopausal women

In this study, the authors investigated whether combined information on reproductive factors has additive value to the single reproductive factor age at menopause for assessing endogenous estrogen exposure and cardiovascular mortality risk in postmenopausal women. They conducted a population-based cohort study that included 9,450 postmenopausal women from Nijmegen, the Netherlands, who were aged 35--65 years at enrollment in 1975, with a median follow-up of 20.5 years. A Cox proportional hazards model and Receiver Operating Curves were used to analyze the data. Women aged 52 years or more at menopause had an 18% reduction in cardiovascular mortality (hazard ratio = 0.82, 95% confidence interval (CI): 0.69, 0.98) compared with those aged 44 years or less. Women with more than 18 years of exposure to endogenous estrogen had a statistically significant 20% reduction in cardiovascular mortality (hazard ratio = 0.80, 95 percent CI: 0.67, 0.96) compared with those who had 13 years of exposure or less. The area under the curve of the Receiver Operating Curves for the two models was identical (area under the curve = 0.67, 95 percent CI: 0.66, 0.68). This study shows that age at menopause is related to cardiovascular disease mortality and that a newly developed composite measure of endogenous estrogen exposure does not add to the predictive value of age at menopause for cardiovascular mortality.     

Usual dietary isoflavone intake is associated with cardiovascular disease risk factors in postmenopausal women

Intervention data suggest a cardioprotective role for supplemental isoflavones; however, few studies have examined the cardiovascular disease (CVD) benefit of usual dietary isoflavone intake. This cross-sectional study examined the association between usual dietary isoflavone intake and CVD risk factors, including lipids and lipoproteins, body mass index (BMI) and fat distribution, blood pressure, glucose and insulin. Subjects were postmenopausal women (n = 208) aged 45-74 y, who attended screening and baseline visits for a randomized, double-blind, placebo-controlled trial examining the effects of isoflavone use. At screening, total cholesterol, triglycerides, HDL cholesterol and LDL cholesterol were measured, and demographic, behavioral and menopausal characteristics were assessed. One month later, dietary intake over the past year was assessed with a standardized questionnaire. Anthropometric measurements and blood pressure were obtained, and a 75-g oral glucose tolerance test was administered. Isoflavone consumption did not vary by age, exercise, smoking, education or years postmenopausal. Women with high genistein intake had a significantly lower BMI (P-trend = 0.05), waist circumference (P-trend = 0.05) and fasting insulin (P-trend = 0.07) than those with no daily genistein consumption. In adjusted analyses, genistein, daidzein and total isoflavone intake were each positively associated with HDL cholesterol (P = 0.05) and inversely associated with postchallenge insulin (P = 0.05). These data suggest a protective role for dietary soy intake against CVD in postmenopausal women.     

Physical activity and mortality: a prospective study among women

OBJECTIVES: This study examined the association between recreational physical activity and mortality in middle-aged and older women and the possibility that physical activity serves as an important marker of health. METHODS: Analyses were conducted among participants in the Nurses' Health Study. Levels of physical activity were assessed by questionnaire in 1980 and updated every 2 to 4 years. RESULTS: Levels of physical activity were inversely associated with mortality risk; however, each activity level above the reference level had approximately the same level of risk reduction (20%-30%). The inverse association was stronger for cardiovascular deaths than for cancer deaths and was strongest for respiratory deaths. Women who died of noncardiovascular, noncancer causes were more likely to have reported that poor health limited their physical activity than were women who died of other causes or who remained alive. CONCLUSIONS: Part of the link between physical activity and mortality risk is probably spurious and difficult to remove analytically; however, on the basis of epidemiologic evidence, much of the health benefit of activity is real.     

农村男性人群体质指数与心血管疾病死亡关系的前瞻性随访研究

目的 探究农村男性人群体质指数和心血管疾病死亡风险的关系。方法 以唐河、凤凰县农村地区纳入“影响成年人死亡相关危险因素的前瞻性研究”项目的22 282名≥40岁的男性人群为研究对象,应用Cox比例风险回归模型计算基线不同BMI分组的人群在随访期间的心血管疾病（CVD）死亡的风险（HR）值。结果 研究对象人群随访年限为（19.1±8.7）年,随访期间共死亡10 828人,死亡比例为48.6%,有4 504例死亡归因于心血管疾病。其中1 279例死于缺血性心脏病（IHD）,1 201例死于缺血性卒中（IS）,1 317例死于出血性卒中（HS）,707例死于其他心血管疾病。用Cox比例风险回归模型（调整地区、年龄、民族、文化程度、职业、吸烟、饮酒、血压等因素）进行多因素分析显示,以BMI<18 kg/m²为参照,当20 kg/m²≤BMI<22 kg/m²时患CVD的死亡风险最低,HR=0.95（95% CI：0.83~1.09）,但从统计学分析,各组BMI的死亡风险差异均无统计学意义（P>0.05）;当20 kg/m²≤BMI<22 kg/m²时人群患IHD的死亡风险最低,HR=0.64（95% CI：0.52~0.80）（P<0.05）,当BMI≥24 kg/m²时人群IHD死亡风险与BMI<18 kg/m²人群的风险之间差异无统计学意义（P>0.05）;IS死亡风险与人群BMI变化无显著性差异（P>0.05）;当18 kg/m²≤BMI<24 kg/m²时人群患HS的死亡风险高于BMI<18 kg/m²组人群（P<0.05）,其中26 kg/m²≤BMI<28 kg/m²时人群患HS死亡风险最高,HR=1.88（95% CI：1.18~2.99）。结论 偏瘦或正常体重人群的CVD、IHD的死亡风险最低,超重人群的HS死亡风险较高,保持合理体重可降低心血管疾病患者的死亡风险。     

A prospective study of high blood pressure and cardiovascular disease in women

The relation of self-reported high blood pressure to the subsequent development of coronary heart disease and stroke was examined in a cohort of 119,963 women, aged 30-55 years, who were initially free from cardiovascular disease. Participants in the Nurses' Health Study reported high blood pressure and other cardiovascular risk factors on baseline questionnaires mailed in 1976. During six years of follow-up, there were 308 incident cases of coronary heart disease (66 fatal and 242 nonfatal myocardial infarctions) and 175 strokes (50 fatal and 125 nonfatal). Fatal as well as nonfatal coronary heart disease and stroke were all significantly more frequent among the women who had reported high blood pressure. After adjusting simultaneously for age and other risk factors, the relative risks were 3.5 (95% confidence interval (Cl) 2.8-4.5) for total coronary heart disease and 2.6 (95% Cl 1.8-3.5) for total stroke. This association was evident at all levels of relative weight. The results emphasize the importance of high blood pressure as an independent predictor of coronary heart disease and stroke in middle-aged women and suggest that the increased risk occurs in both lean and obese women.     

Alcohol intake and cardiovascular disease and mortality: the role of pre-existing disease

OBJECTIVES: Pre-existing conditions have been postulated as possible causes of the J-shaped relationship between alcohol intake and cardiovascular disease. Two research questions have been addressed in this paper. First, whether never drinkers and former drinkers differ from moderate drinkers in terms of health, and if so, which health problems contribute to this difference. Second, whether the U-shaped relationship between current alcohol intake and cardiovascular disease or all-cause mortality could in part be explained by difference in pre-existing disease burden. DESIGN, SETTING AND PARTICIPANTS: A prospective case-cohort, the Lifestyle and Health Study, consisting of 16,210 men and women aged between 45 and 70 years. Alcohol intake and risk factors were assessed at baseline with a self-administered questionnaire. Medical information was obtained from general practitioners. Cardiovascular events and mortality were followed for a period of 5 years (1996-2001). MAIN RESULTS: Never drinkers and former drinkers were less healthy than moderate drinkers. They rated their health more often as poor, and often had more diseases, such as cardiovascular disease, diabetes, and also alcohol-related diseases. The difference in disease burden did not change the observed relationship between alcohol intake and cardiovascular events, and only partially changed the U-shaped relationship between alcohol intake and all-cause mortality. CONCLUSIONS: The found difference in health between never drinkers and former drinkers compared with moderate drinkers appeared to be only a partial explanation of the observed relationships between alcohol intake and cardiovascular disease, and between alcohol intake and all-cause mortality.     

Dietary folate intake, alcohol, and risk of breast cancer in a prospective study of postmenopausal women.

Low B-vitamin intake may increase risk of breast cancer through decreased DNA repair capacity. Alcohol intake increases risk for breast cancer, with evidence from prospective studies of an interaction between alcohol and folate. We explored dietary intake of folate and other B vitamins with risk of breast cancer in a cohort study of 34,387 postmenopausal women. To measure diet, we mailed a food frequency questionnaire; we estimated nutrient intakes and categorized them into four levels: <10th, 11th-30th, 31st-50th, and >50th percentiles. Through 12 years of follow-up, we identified 1,586 cases of breast cancer in the cohort at risk. We estimated relative risks (RRs) and 95% confidence intervals (CIs) through Cox regression models adjusted for age, energy, and other risk factors. Women in the lowest 10th percentile of folate intake from diet alone were at modestly increased risk of breast cancer relative to those above the 50th percentile: RR = 1.21 (95% CI = 0.91--1.61). We examined the joint association of folate intake and alcohol use on risk of breast cancer, with the reference group defined as women with high folate (>50th percentile) and no alcohol use. The RRs of breast cancer associated with low dietary folate intake were 1.08 (95% CI = 0.78--1.49) among nondrinkers, 1.33 (95% CI = 0.86--2.05) among drinkers of < or = 4 gm per day, and 1.59 (95% CI = 1.05--2.41) among drinkers of > 4 gm per day. These results suggest that the risks of postmenopausal breast cancer may be increased among women with low intakes of folate if they consume alcohol-containing beverages.     

Dairy intake in relation to cardiovascular disease mortality and all-cause mortality: the Hoorn Study

Purpose

Existing data from prospective cohort studies on dairy consumption and cardiovascular diseases are inconsistent. Even though the association between total dairy and cardiovascular diseases has been studied before, little is known about the effect of different types of dairy products on cardiovascular diseases (CVD). The objective of this study was to examine the relationship between (type of) dairy intake and CVD mortality and all-cause mortality in a Dutch population.

Methods

We examined the relationship between dairy intake and CVD mortality and all-cause mortality in 1956 participants of the Hoorn Study (aged 50–75 years), free of CVD at baseline. Hazard ratios with 95 % CIs were obtained for CVD mortality and all-cause mortality per standard deviation (SD) of the mean increase in dairy intake, with adjustment for age, sex, BMI, smoking, education, total energy intake, alcohol consumption, physical activity, and dietary intakes.

Results

During 12.4 years of follow-up, 403 participants died, of whom 116 had a fatal CVD event. Overall dairy intake was not associated with CVD mortality or all-cause mortality. Each SD increase in high-fat dairy intake was associated with a 32 % higher risk of CVD mortality (95 % CI; 7–61 %).

Conclusion

In this prospective cohort study, the intake of high-fat dairy products was associated with an increased risk of CVD mortality.     

Dipstick proteinuria as a predictor of all-cause and cardiovascular disease mortality in Bangladesh: A prospective cohort study

ObjectiveBaseline, persistent, incident, and remittent dipstick proteinuria have never been tested as predictors of mortality in an undeveloped country. The goal of this study was to determine which of these four types of proteinuria (if any) predict mortality.MethodsBaseline data was collected from 2000 to 2002 in Bangladesh from 11,121 adults. Vital status was ascertained over 11–12 years. Cox models were used to evaluate proteinuria in relation to all-cause and cardiovascular disease (CVD) mortality. CVD mortality was evaluated only in those with baseline proteinuria. Persistent, remittent, and incident proteinuria were determined at the 2-year exam.ResultsBaseline proteinuria of 1 + or greater was significantly associated with all-cause (hazard ratio (HR) 2.87; 95% C.I., 1.71–4.80) and CVD mortality (HR: 3.55; 95% C.I., 1.81–6.95) compared to no proteinuria, adjusted for age, gender, arsenic well water concentration, education, hypertension, BMI, smoking, and diabetes mellitus. Persistent 1 + proteinuria had a stronger risk of death, 3.49 (1.64–7.41)-fold greater, than no proteinuria. Incident 1 + proteinuria had a 1.87 (0.92–3.78)-fold greater mortality over 9–10 years. Remittent proteinuria revealed no increased mortality.ConclusionsBaseline, persistent, and incident dipstick proteinuria were predictors of all-cause mortality with persistent proteinuria having the greatest risk. In developing countries, those with 1 + dipstick proteinuria, particularly if persistent, should be targeted for definitive diagnosis and treatment. The two most common causes of proteinuria to search for are diabetes mellitus and hypertension.     

Relationships of age at menarche and menopause, and reproductive year with mortality from cardiovascular disease in Japanese postmenopausal women: the JACC study

BACKGROUND: Early menopause is associated with increased risk of coronary heart disease in Caucasian women. However, this association has not been examined in Asian women. METHODS: We conducted a 10-year cohort study of 37,965 Japanese post-menopausal women aged 40-79 years in the Japan Collaborative Cohort (JACC) Study. Causes of death were determined based on the International Classification of Disease. RESULTS: There were 487 mortality of stroke and 178 mortality of coronary heart disease. Late menarche or early menopause, or shorter duration of reproductive period was not associated with risk of mortality from coronary heart disease. However, compared with women with age at menarche < or =13 years, those with age at menarche > or =17 years tended to have increased risk of mortality from stroke: the multivariable hazard ratio was 1.32 (95% confidence interval [CI]: 0.93-1.87, p = 0.10). Compared with women with age at menopause of > or =49 years, those with age at menopause of <49 years tended to have increased risk of coronary heart disease among women aged 40-64 years; the multivariable hazard ratio was 1.85 (95% CI: 0.92-3.73, p = 0.08). CONCLUSIONS: The possible association between early menopause and coronary heart disease among middle-aged women was consistent with the result of observational studies for Caucasian women, and can be explained by a protective effect of endogenous estrogen on the development of atherosclerosis.