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Background: Dietary fiber is part of a healthy diet and may exert a protective effect in the cardiovascular system. The effect of fiber intake on blood pressure (BP) has not yet been established., Methods: We performed a meta-analysis of randomized placebo-controlled trials to estimate the effect of fiber supplementation on BP overall and in population subgroups. Original articles published between January 1, 1966, and January 1, 2003, were retrieved for 24 trials that fulfilled criteria for meta-analysis. Data were abstracted on fiber dose, fiber type, BP changes, study design features, and study population characteristics. A random-effects model was used for meta-analysis., Results: Fiber supplementation (average dose, 11.5 g/d) changed systolic BP by -1.13 mm Hg (95% confidence interval: -2.49 to 0.23) and diastolic BP by -1.26 mm Hg (-2.04 to -0.48). Reductions in BP tended to be larger in older (>40 years) and in hypertensive populations than in younger and in normotensive ones., Conclusion: Increasing the intake of fiber in Western populations, where intake is far below recommended levels, may contribute to the prevention of hypertension.

Vitamin K-dependent proteins, including matrix Gla-protein, have been shown to inhibit vascular calcification. Activation of these proteins via carboxylation depends on the availability of vitamin K. We examined whether dietary intake of phylloquinone (vitamin K-1) and menaquinone (vitamin K-2) were related to aortic calcification and coronary heart disease (CHD) in the population-based Rotterdam Study. The analysis included 4807 subjects with dietary data and no history of myocardial infarction at baseline (1990-1993) who were followed until January 1, 2000. The risk of incident CHD, all-cause mortality, and aortic atherosclerosis was studied in tertiles of energy-adjusted vitamin K intake after adjustment for age, gender, BMI, smoking, diabetes, education, and dietary factors. The relative risk (RR) of CHD mortality was reduced in the mid and upper tertiles of dietary menaquinone compared to the lower tertile [RR = 0.73 (95% CI: 0.45, 1.17) and 0.43 (0.24, 0.77), respectively]. Intake of menaquinone was also inversely related to all-cause mortality [RR = 0.91 (0.75, 1.09) and 0.74 (0.59, 0.92), respectively] and severe aortic calcification [odds ratio of 0.71 (0.50, 1.00) and 0.48 (0.32, 0.71), respectively]. Phylloquinone intake was not related to any of the outcomes. These findings suggest that an adequate intake of menaquinone could be important for CHD prevention.

Background: Major depression is known to be related to higher cardiovascular mortality. However, epidemiological data regarding dispositional optimism in relation to mortality are scanty., Objective: To test whether subjects who are optimistic live longer than those who are pessimistic., Design: Our analysis formed part of a prospective population-based cohort study in the Netherlands (Arnhem Elderly Study)., Setting: General community., Participants: Elderly subjects aged 65 to 85 years (999 men and women) completed the 30-item validated Dutch Scale of Subjective Well-being for Older Persons, with 5 subscales: health, self-respect, morale, optimism, and contacts. A total of 941 subjects (466 men and 475 women) had complete dispositional optimism data, and these subjects were divided into quartiles., Main Outcome Measure: Number of deaths during the follow-up period., Results: During the follow-up period of 9.1 years (1991-2001), there were 397 deaths. Compared with subjects with a high level of pessimism, those reporting a high level of optimism had an age- and sex-adjusted hazard ratio of 0.55 (95% confidence interval, 0.42-0.74; upper vs lower quartile) for all-cause mortality. For cardiovascular mortality, the hazard ratio was 0.23 (95% confidence interval, 0.10-0.55) when adjusted for age, sex, chronic disease, education, smoking, alcohol consumption, history of cardiovascular disease or hypertension, body mass index, and total cholesterol level. Protective trend relationships were observed between the level of optimism and all-cause and cardiovascular mortality (P<.001 and P = .001 for trend, respectively). Interaction with sex (P = .04) supported a stronger protective effect of optimism in men than women for all-cause mortality but not for cardiovascular mortality., Conclusions: Our results provide support for a graded and independent protective relationship between dispositional optimism and all-cause mortality in old age. Prevention of cardiovascular mortality accounted for much of the effect.

Background: Data on the impact of the many dietary and lifestyle factors on the prevalence of hypertension in Western societies are lacking. This study quantified the contributions of body weight, physical inactivity and dietary factors to the prevalence of hypertension in Finland, Italy, the Netherlands, United Kingdom (UK) and USA., Methods: Distributions of blood pressure (BP) and risk factors in Western populations were obtained from nationwide surveys. The effect of risk factors on BP was assessed by meta-regression analysis of randomized trials, published between 1966 and March 2001. Population attributable risk percentages (PAR%) for hypertension (i.e. systolic BP > or =140 mmHg) were computed for all risk factors in the five countries., Results: Being overweight made the largest contribution to hypertension, with PAR% between 11% (Italy) and 25% (USA). PAR% were 5-13% for physical inactivity, 9-17% for high sodium intake, 4-17% for low potassium intake and 4-8% for low magnesium intake. The impact of alcohol was small (2-3%) in all populations. PAR% varied among populations for inadequate intake of calcium (2-8%), magnesium (4-8%), coffee (0-9%) and fish fatty acids (3-16%)., Conclusions: Diet and lifestyle have a substantial impact on hypertension in Western societies, with being overweight, physical inactivity, high sodium intake and low potassium intake being the main contributors. The relative significance of different risk factors varies among populations, which is important for preventative strategies.

The habitual level of PAI-1 is influenced by many factors, of which obesity and insulin resistance are the most important. It is possible to reduce plasma PAI-1 by changes in life style, e.g. weight reduction and physical activity. Data on potential interactions between environmental and metabolic variables on one hand, and the 4G/5G-polymorphism on the other hand, are still scarce. It becomes more and more clear that PAI-1 may possibly not be a major (causal) factor in cardiovascular disease, but its role in inflammation deserves further attention. In the presence of the 4G-allele not only the PAI-1 response was more pronounced, but also the response of other acute-phase reactants, which implies that the increases of these reactants are secondary to the increase in PAI-1. A myocardial infarction also provokes an acute phase response. It can thus be hypothesized that the 4G-allele might exacerbate tissue injury during the acute phase after a myocardial infarction, and thereby negatively affect the prognosis.

Background and Purpose: Plasminogen activator inhibitor type 1 (PAI-1) is the main inhibitor of fibrinolysis, and high levels may increase the risk of cardiovascular disease. The 4G/5G polymorphism affects PAI-1 gene transcription with lower levels of plasma PAI-1 in the presence of the 5G allele. We investigated whether plasma PAI-1 and 4G/5G genotype would predict the occurrence of cardiovascular events at old age., Methods: Relative risks for cardiovascular events and all-cause mortality were obtained in strata of PAI-1 activity and 4G/5G genotype in a population-based study of 637 Dutch elderly with 7.8 years of follow-up., Results: The 4G/4G genotype was associated with a decreased risk of stroke (relative risk [RR]=0.4; 95% CI, 0.2 to 0.9), transient ischemic attack (RR=0.3; 95% CI, 0.1 to 0.8), and cardiovascular mortality (RR=0.5; 95% CI, 0.3 to 1.0) after adjustment for age, sex, and time of blood sampling. 4G carriers had an increased risk of myocardial infarction, but this was not statistically significant. Subjects with high plasma PAI-1 activity were at increased risk of stroke (RR=3.3 in highest versus lowest tertile; 95% CI, 1.5 to 7.1), cardiovascular mortality (RR=2.3; 95% CI, 1.2 to 4.4), and all-cause mortality (RR=1.5; 95% CI, 1.1 to 2.1)., Conclusions: Our results provide support for a protective effect of the 4G allele against stroke, which is notable given the direct relationship between stroke and PAI-1 activity. We hypothesize that a local increase in tissue PAI-1 associated with the 4G allele may stabilize plaques, thereby reducing the risk of cerebrovascular disease.

Increased body weight is a strong risk factor for hypertension. A meta-analysis of randomized controlled trials was performed to estimate the effect of weight reduction on blood pressure overall and in population subgroups. Twenty-five randomized, controlled trials (comprising 34 strata) published between 1966 and 2002 with a total of 4874 participants were included. A random-effects model was used to account for heterogeneity among trials. A net weight reduction of -5.1 kg (95% confidence interval [CI], -6.03 to -4.25) by means of energy restriction, increased physical activity, or both reduced systolic blood pressure by -4.44 mm Hg (95% CI, -5.93 to -2.95) and diastolic blood pressure by -3.57 mm Hg (95% CI, -4.88 to -2.25). Blood pressure reductions were -1.05 mm Hg (95% CI, -1.43 to -0.66) systolic and -0.92 mm Hg (95% CI, -1.28 to -0.55) diastolic when expressed per kilogram of weight loss. As expected, significantly larger blood pressure reductions were observed in populations with an average weight loss >5 kg than in populations with less weight loss, both for systolic (-6.63 mm Hg [95% CI, -8.43 to -4.82] vs -2.70 mm Hg [95% CI, -4.59 to -0.81]) and diastolic (-5.12 mm Hg [95% CI, -6.48 to -3.75] vs -2.01 mm Hg [95% CI, -3.47 to -0.54]) blood pressure. The effect on diastolic blood pressure was significantly larger in populations taking antihypertensive drugs than in untreated populations (-5.31 mm Hg [95% CI, -6.64 to -3.99] vs -2.91 mm Hg [95% CI, -3.66 to -2.16]). This meta-analysis clearly shows that weight loss is important for the prevention and treatment of hypertension.

The objective of the study was to assess the blood pressure response to changes in sodium and potassium intake and examine effect modification by age, gender, blood pressure, body weight and habitual sodium and potassium intake. Randomised trials of sodium reduction or potassium supplementation and blood pressure were identified through reference lists of systematic reviews and an additional MEDLINE search (January 1995-March 2001). A total of 40 sodium trials and 27 potassium trials in adults with a minimum duration of 2 weeks were selected for analysis. Data on changes in electrolyte intake and blood pressure during intervention were collected, as well as data on mean age, gender, body weight, initial electrolyte intake and initial blood pressure of the trial populations. Blood pressure effects of changes in electrolyte intake were assessed by weighted metaregression analysis, overall and in strata of trial population characteristics. Analyses were repeated with adjustment for potential confounders. Sodium reduction (median: -77 mmol/24 h) was associated with a change of -2.54 mmHg (95% CI: -3.16, -1.92) in systolic blood pressure and -1.96 mmHg (-2.41, -1.51) in diastolic blood pressure. Corresponding values for increased potassium intake (median: 44 mmol/24 h) were -2.42 mmHg (-3.75, -1.08) and -1.57 mmHg (-2.65, -0.50). Blood pressure response was larger in hypertensives than normotensives, both for sodium (systolic: -5.24 vs -1.26 mmHg, P < 0.001; diastolic: -3.69 vs -1.14 mmHg, P < 0.001) and potassium (systolic: -3.51 vs -0.97 mmHg, P=0.089; diastolic: -2.51 vs -0.34 mmHg, P=0.074). In conclusion, reduced intake of sodium and increased intake of potassium could make an important contribution to the prevention of hypertension, especially in populations with elevated blood pressure.

Hypertension, defined as a blood pressure > or = 140/90 mmHg upon repeated measurement or the use of antihypertensive medication, is present in 14% of Dutch adults. A healthy diet plays an important role in both the prevention and treatment of hypertension. Under controlled conditions, very good results have been obtained with the 'Dietary approaches to stop hypertension' (DASH) combination diet, which has recently been developed in the United States. The DASH combination diet contains large amounts of fruit, vegetables, fish and nuts, low-fat dairy products and reduced levels of total and saturated fat. This dietary pattern yielded blood pressure reductions of 11.4/5.5 mmHg in mildly hypertensive patients. Intervention studies have shown a favourable effect of salt reduction on blood pressure in hypertensive patients, even in the case of mild hypertension. Simultaneous increases in potassium and magnesium intake could have an additional beneficial effect. The use of a low-sodium, high-potassium mineral salt could make a useful contribution to the prevention and treatment of hypertension. In case of hypertension, it is further recommended to reduce the intake of liquorice to less than 50 g per day. These dietary measures, combined with weight loss and physical exercise, may prevent drug treatment in patients with mild hypertension.

Plasma total homocysteine (tHcy) levels are on average lower in women versus men, indicating an estrogenic effect. Oral estrogens (absorbed via the liver) may be hypothesized to have stronger effects on hepatic homocysteine metabolism than transdermal estrogens. We randomly assigned 30 male-to-female transsexuals (20-44 years old) to 4 months' administration of oral ethinyl estradiol (n=15) or transdermal 17beta-estradiol (n=15), both with the antiandrogen cyproterone acetate (CA). Ten other male controls were treated with CA only. At baseline and after 2 and 4 months, plasma tHcy was analyzed in conjunction with plasma folate. Oral ethinyl estradiol and transdermal 17beta-estradiol similarly reduced plasma tHcy (geometric mean 10.6 micromol/l [95% CI 8.2-13.9] to 7.5 [6.5; 8.8], and 11.3 [8.1; 16.4] to 8.4 [6.5; 11.1]; P<0.001 for both), whereas CA had no effects. No effects were found on folate levels. Thus, oral and transdermal estrogens decrease plasma tHcy to a similar degree (by geometric mean -26%), which suggests that a hepatic mechanism is unlikely to play an important role in the decline of tHcy levels.

We examined the diurnal pattern in Plasminogen Activator Inhibitor-type 1 (PAI-1) activity and Plasminogen activator (t-PA) in relation to the 4G/5G-polymorphism in the promoter of the PAI-1 gene. The analyses were performed in the Arnhem Elderly Study, a population-based study of 598 elderly. A single blood sample was drawn and the time of blood sampling was recorded (between 8 a.m. and 5.30 p.m.). Plasma PAI-1 activity was strongly associated with time of blood sampling, showing the highest values in the early morning. The diurnal pattern was clearly present in the 4G/4G (n = 184) and 4G/5G (n = 275) genotypes, but not in the 5G/5G-genotype (n = 139). T-PA antigen showed a weak diurnal variation, which did not differ across the variants of the 4G/5G-polymorphism. Our findings raise the hypothesis that 5G-homozygotic persons may be relatively protected from diurnal variation in the occurrence of coronary events.

Objective: The antihypertensive effect of fish oil was estimated from randomized trials using metaregression analysis. Modification of the blood pressure (BP) effect by age, gender, blood pressure, and body mass index was examined., Methods: A total of 90 randomized trials of fish oil and BP were identified through MEDLINE (1966-March 2001). Trials with co-interventions, patient populations, non-placebo controls, or duration of < 2 weeks were excluded. A total of 36 trials (50 strata) were included, 22 of which had a double-blind design. Original reports were retrieved for data collection on sample size, study design, duration, fish oil dose, BP changes and baseline characteristics of trial populations. Pooled BP estimates were obtained by metaregression analysis, weighted for trial sample sizes. Stratified analyses according to population characteristics were performed., Results: Intake of fish oil was high in most trials (median dose: 3.7 g/day). Fish oil reduced systolic BP by 2.1 mmHg [95% confidence interval (CI): 1.0, 3.2; P < 0.01] and diastolic BP by 1.6 mmHg (95% CI: 1.0. 2.2; P < 0.01). Restricting the analysis to double-blind trials yielded BP reductions of 1.7 mmHg (95% CI: 0.3, 3.1) and 1.5 mmHg (95% CI: 0.6, 2.3), respectively. BP effects tended to be larger in populations that were older (> 45 years) and in hypertensive populations (BP >or= 140/90 mmHg)., Conclusions: High intake of fish oil may lower BP, especially in older and hypertensive subjects. The antihypertensive effect of lower doses of fish oil (< 0.5 g/day) however, remains to be established.

Background: Dietary flavonoids may protect against cardiovascular disease, but evidence is still conflicting. Tea is the major source of flavonoids in Western populations., Objective: The association of tea and flavonoid intake with incident myocardial infarction was examined in the general Dutch population., Design: A longitudinal analysis was performed with the use of data from the Rotterdam Study-a population-based study of men and women aged >or=55 y. Diet was assessed at baseline (1990-1993) with a validated semiquantitative food-frequency questionnaire. The analysis included 4807 subjects with no history of myocardial infarction, who were followed until 31 December 1997. Data were analyzed in a Cox regression model, with adjustment for age, sex, body mass index, smoking status, pack-years of cigarette smoking, education level, and daily intakes of alcohol, coffee, polyunsaturated fat, saturated fat, fiber, vitamin E, and total energy., Results: During 5.6 y of follow-up, a total of 146 first myocardial infarctions occurred, 30 of which were fatal. The relative risk (RR) of incident myocardial infarction was lower in tea drinkers with a daily intake >375 mL (RR: 0.57; 95% CI: 0.33, 0.98) than in nontea drinkers. The inverse association with tea drinking was stronger for fatal events (0.30; 0.09, 0.94) than for nonfatal events (0.68; 0.37, 1.26). The intake of dietary flavonoids (quercetin + kaempferol + myricetin) was significantly inversely associated only with fatal myocardial infarction (0.35; 0.13, 0.98) in upper compared with lower tertiles of intake., Conclusions: An increased intake of tea and flavonoids may contribute to the primary prevention of ischemic heart disease.

The risk of hemorrhage when using coumarin anticoagulants sharply increases when the International Normalized Ratio (INR) is > or =6.0. We performed a case-control study among outpatients of an anticoagulation clinic to identify sociodemographic-, lifestyle-, and dietary factors related to overanticoagulation. Three hundred cases with an INR > or =6.0 were compared with 302 randomly selected matched controls with an INR within the target zone. Age, sex, and level of education were not associated with overanticoagulation. Body mass index was negatively related to overanticoagulation, a beneath-average level of physical activity was positively related to overanticoagulation and never-smokers were more likely to have an INR > or =6.0 compared with smokers. Habitual alcohol consumption, even heavy drinking, was not related to overanticoagulation. However, a recent decrease of alcohol intake increased the risk of an INR > or =6.0. In addition, weight loss and a vacation were risk factors for overanticoagulation. Dietary factors were not associated with overanticoaguation. If risk factors can not be avoided, increased monitoring of INR values could prevent overanticoagulation and potential bleeding complications.

Recent studies have shown that a low bone mineral density (BMD) is associated with a higher risk of mortality. Most studies have investigated this relationship in women only and presented their risk estimates per standard deviation change in BMD. However, when using this approach, a BMD threshold might be missed when relative risks are presented in the traditional manner. Therefore, in this study our aim was to model the relation between BMD and all-cause mortality. In the Rotterdam Study, follow-up was complete for 5819 men and women aged > or =55 years for whom BMD data were available. During an average follow-up of 5.4 years, 399 men and 317 women died. We calculated BMD Z scores using measurements performed at the femoral neck. Cox proportional hazards regression was used to fit the model. An average BMD, reflected by a Z score = 0, was used as the reference. For women, no significant relationship between BMD and overall mortality was observed. For men, however, a cubic model best fitted the relationship under study, also after adjusting for age and body mass index (BMI). The risk of mortality increased when BMD was below average. Similar results were found when separate curves were made for diabetics and nondiabetics, smokers (ever or never), and tertiles of BMI. Excluding subjects who had suffered hip fractures, or adjusting for the number of drugs used and for lower limb disability, essentially did not change results. This suggests that low BMD is not mainly due to morbidity and impaired mobility in our cohort, which makes this a less likely explanation for the observed relation with mortality. The results of our study suggest that, in men, a nonlinear relationship between BMD and mortality exists, which is independent of comorbidity, whereas, in women, no significant relationship was observed.

Moderate alcohol consumption is associated with a reduced risk of cardiovascular disease. Data on alcohol consumption and atherosclerosis are scarce. To determine the association between alcohol consumption and risk of peripheral arterial disease, the authors carried out a cross-sectional study (1990-1993) in the population-based Rotterdam Study among men and women aged 55 years or over. Data on alcohol consumption and peripheral arterial disease, as measured by the ankle/brachial blood pressure index, were available for 3,975 participants without symptomatic cardiovascular disease. Male drinkers consumed beer, wine, and liquor, while female drinkers consumed predominantly wine and fortified wine types. An inverse relation between moderate alcohol consumption and peripheral arterial disease was found in women but not in men. Because of residual confounding by smoking, analyses were repeated in nonsmokers. In nonsmoking men, odds ratios were 0.86 (95% confidence interval (CI): 0.46, 1.63) for daily alcohol consumption up to and including 10 g, 0.75 (95% CI: 0.37, 1.55) for 11-20 g, and 0.68 (95% CI: 0.35, 1.34) for more than 20 g, compared with nondrinking. In nonsmoking women, corresponding odds ratios were 0.65 (95% CI: 0.48, 0.87), 0.66 (95% CI: 0.42, 1.05), and 0.41 (95% CI: 0.21, 0.77), respectively. In conclusion, an inverse association between alcohol consumption and peripheral arterial disease was found in nonsmoking men and women.

High circulating levels of carotenoids have been thought to exhibit a protective function in the development of atherosclerosis. We investigated whether aortic atherosclerosis was associated with lower levels of the major serum carotenoids in alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein, lycopene, and zeaxanthin-in a subsample of the elderly population of the Rotterdam Study. Aortic atherosclerosis was assessed by presence of calcified plaques of the abdominal aorta. The case-control analysis comprised 108 subjects with aortic atherosclerosis and controls. In an age- and sex-adjusted logistic regression model, serum lycopene was inversely associated with the risk of atherosclerosis. The odds ratio for the highest compared to the lowest quartile of serum lycopene was 0.55 (95% CI 0.25-1.22; p(trend)=0.13). Multivariate adjustment did not appreciably alter these results. Stratification by smoking status indicated that the inverse association between lycopene and aortic calcification was most evident in current and former smokers (OR=0.35; 95% CI 0.13-0.94; p(trend)=0.04). No association with atherosclerosis was observed for quartiles of serum concentrations of alpha-carotene, beta-carotene, lutein, and zeaxanthin. In conclusion, this study provides evidence for a modest inverse association between levels of serum lycopene and presence of atherosclerosis, the association being most pronounced in current and former smokers. Our findings suggest that lycopene may play a protective role in the development of atherosclerosis.

Background: Epidemiological studies have indicated a protective role of dietary flavonoids in cardiovascular disease, but evidence is still conflicting. Tea is the major dietary source for flavonoids in Western populations. We studied the association of tea intake with aortic atherosclerosis in a general population., Methods: The present analysis formed part of the Rotterdam Study, a prospective study of men and women 55 years and older. Dietary intakes were assessed at baseline by a trained dietician who used a semiquantitative food frequency questionnaire. Calcified plaques in the abdominal aorta were radiographically detected after 2 to 3 years of follow-up. Aortic atherosclerosis was classified as "mild," "moderate," or "severe," according to the length of the calcified area (<1 cm, 1-5 cm, and >5 cm, respectively). The association of tea intake with severity of aortic atherosclerosis was studied in 3454 subjects who were free of cardiovascular disease at baseline. Data were analyzed by logistic regression, adjusting for age, sex, body mass index (calculated as weight in kilograms divided by the square of height in meters), smoking, education, and intake of alcohol, coffee, vitamin antioxidants, total fat, and total energy., Results: Multivariable analyses showed a significant, inverse association of tea intake with severe aortic atherosclerosis. Odds ratios decreased from 0.54 (95% confidence interval [CI], 0.32-0.92) for drinking 125 to 250 mL (1-2 cups) of tea to 0.31 (CI, 0.16-0.59) for drinking more than 500 mL/d (4 cups per day). The associations were stronger in women than in men. The association of tea intake with mild and moderate atherosclerosis was not statistically significant., Conclusion: This study indicates a protective effect of tea drinking against ischemic heart disease.

The relationship of high salt intake to elevated blood pressure levels has been demonstrated in most populations by cross-sectional, longitudinal, physiological, and clinical intervention studies. Variation within the angiotensinogen gene has been implicated in the genetic control of blood pressure levels and has been suggested to contribute to increased salt sensitivity. A total of 86 hypertensive men and women who had never been treated and who had participated in a 6-month randomized, placebo-controlled, clinical trial of low-sodium mineral salt (19% reduction in urinary sodium versus 12% increase in placebo group) were genotyped at the angiotensinogen M235T locus to test the hypothesis that the 235T allele is associated with a significant blood pressure response to a sodium reduction intervention whereas the 235M allele is not. After adjustment for gender and baseline blood pressure, persons with the TT and MT genotypes showed significant systolic blood pressure reductions on mineral salt compared with control subjects (P = .02 and P = .001, respectively) but not persons with the MM genotype (P = .10). Net adjusted diastolic blood pressure reductions also showed greater significance for persons with the TT and MT genotypes than for persons with the MM genotype (P = .08, P = .01, and P = .83, respectively). The net adjusted systolic and diastolic blood pressure reduction was -8.6/-3.9 mm Hg for persons with the TT genotype, -9.0/-5.2 mm Hg for the MT genotype, and -5.3/-1.0 mm Hg for the MM genotype. We conclude that the 235T allele of the angiotensinogen gene is associated with greater blood pressure decreases than the 235M allele after a sodium reduction intervention. The angiotensinogen gene accounts for some of the interindividual variation of the blood pressure response to sodium reduction.

Background: Epidemiologic studies have shown dietary antioxidants to be inversely correlated with ischemic heart disease., Objective: We investigated whether dietary beta-carotene, vitamin C, and vitamin E were related to the risk of myocardial infarction (MI) in an elderly population., Design: The study sample consisted of 4802 participants of the Rotterdam Study aged 55-95 y who were free of MI at baseline and for whom dietary data assessed by a semiquantitative food frequency questionnaire were available. During a 4-y follow-up period, 124 subjects had an MI. The association between energy-adjusted beta-carotene, vitamin C, and vitamin E intakes and risk of MI was examined by multivariate logistic regression., Results: Risk of MI for the highest compared with the lowest tertile of beta-carotene intake was 0.55 (95% CI: 0.34, 0.83; P for trend = 0.013), adjusted for age, sex, body mass index, pack-years, income, education, alcohol intake, energy-adjusted intakes of vitamin C and E, and use of antioxidative vitamin supplements. When beta-carotene intakes from supplements were considered, the inverse relation with risk of MI was slightly more pronounced. Stratification by smoking status indicated that the association was most evident in current and former smokers. No association with risk of MI was observed for dietary vitamin C and vitamin E., Conclusion: The results of this observational study in the elderly population of the Rotterdam Study support the hypothesis that high dietary beta-carotene intakes may protect against cardiovascular disease. We did not observe an association between vitamin C or vitamin E and MI.

Objective: The study was conducted to assess the relative validity of a 170-item semiquantitative food frequency questionnaire (SFFQ) adapted for use in the elderly., Design and Subjects: The study was carried out in a sample of 80 men and women aged 55-75 y participating in a community based prospective cohort study in Rotterdam, The Netherlands. The two-step dietary assessment comprised a simple self-administered questionnaire (20 min) followed by a structured interview with trained dietitians (20 min) based on the completed questionnaire. Multiple food records (FR) collected over a one year period served as reference method. 24 h urine urea was used as indirect marker for protein intake., Results: Compared with FR, the SFFQ generally overestimated nutrient intake as reflected by difference in means and the ratio of SFFQ to FR. Energy adjustment reduced the observed overestimation. Pearson's correlation coefficients varied from close to 0.5 to about 0.9 for crude data, and after adjustment for age, sex, total energy intake, and for within-person variability in daily intake for 0.4-0.8. Cross-classification into quintiles resulted in correct classification into the same or adjacent quintile of 75.8% for crude and 76.8% for energy-adjusted data. Validation of protein intake estimated by SFFQ with protein excretion from 24h urine urea indicated overestimation of protein intake by SFFQ. Spearman correlation coefficient between protein intake estimated from urea excretion and SFFQ was 0.67., Conclusions: Adaptation of a SFFQ for use in the elderly resulted in a valid and time-efficient dietary assessment instrument. Its ability to adequately rank study subjects according to their dietary intake support its application in epidemiological studies in the elderly.

We examined the association of urinary sodium and potassium excretion with blood pressure (BP) in the Rotterdam Study, a population-based study among 7983 men and women aged 55 and over. The present analysis included 1006 subjects with complete BP and urinary data who did not use antihypertensive drugs and did not report themselves to be hypertensive. Electrolyte excretions were assessed in a timed nocturnal urine sample and standardized to 24-h values. The association of electrolyte excretions with BP was studied in a multiple linear regression model with adjustment for age, sex, and body mass index. When sodium and potassium were entered simultaneously into the multivariate model, a 100 mmol increase in potassium was associated with a 9.4 decrease in systolic (P = 0.01) and a 4.9 mm Hg decrease in diastolic BP (P = 0.01). Sodium was directly related to BP, with a 2.2 mm Hg increase in systolic (P = 0.06) and a 0.8 mm Hg increase in diastolic BP (P = 0.14) per 100 mmol. Our findings suggest that an increased intake of potassium and a decrease intake of salt may lower BP at old age.

In 1980, a randomized trial was conducted among 476 Dutch newborn infants to study the effect of a low or normal sodium diet on blood pressure during the first 6 months of life. At the end of the trial, systolic blood pressure in the low sodium group (n = 231) was 2.1 mm Hg lower than in the control group (n = 245). To investigate whether contrasting levels of sodium intake in infancy are associated with blood pressure differences in adolescence, we measured blood pressure in 167 children from the original cohort (35%) after 15 years of follow-up. We assessed the differences in systolic and diastolic blood pressure levels between the diet groups using a multivariate regression model with adjustment for potential confounders. The adjusted systolic blood pressure at follow-up was 3.6 mm Hg lower (95% confidence interval, -6.6 to -0.5) and the diastolic pressure was 2.2 mm Hg lower (95% confidence interval, -4.5 to 0.2) in children who had been assigned to the low sodium group (n = 71) compared with the control group (n = 96). These findings suggest that sodium intake in infancy may be important in relation to blood pressure later in life.

Objective: To examine the relation between dietary electrolyte intake and blood pressure in older people., Methods: The study included 3239 participants of the Rotterdam Study (41% of the total cohort) who were aged over 55 years and had not been prescribed antihypertensive drugs. Their dietary intake was assessed by a semiquantitative food frequency questionnaire. The association of energy-adjusted intakes of potassium, magnesium and calcium with blood pressure was studied in a linear regression model with adjustment for age, sex, body mass index and alcohol intake., Results: An increase in potassium intake of 1 g/day was associated with a 0.9 mmHg lower systolic and a 0.8 mmHg lower diastolic blood pressure. An increase in magnesium intake of 100 mg was associated with a 1.2 mmHg lower systolic and a 1.1 mmHg lower diastolic blood pressure. Calcium intake was not independently related to blood pressure, except for a subgroup of 1360 hypertensive subjects in which a significant inverse association with diastolic blood pressure was observed., Conclusions: Our findings support the view that an increase in the intake of foods rich in potassium and magnesium could lower blood pressure at older age.

We examined the effect of long-term moderate sodium restriction on the HDL/total cholesterol ratio within a randomised trial of the effect of mineral salt on blood pressure (BP). Eighty nine untreated hypertensive men and women aged 55-75 years were included in the analysis. During 24 weeks, 46 subjects used a low sodium, high potassium, high magnesium salt and 43 controls used common salt. Serum cholesterol levels were measured at baseline and at the end of the trial. After 24 weeks, 24 h urinary sodium was decreased by 41 mmol (95% Cl 23-60 mmol, P < 0.0001) in the mineral salt group compared with the controls. Serum total cholesterol was decreased in both groups, but 0.45 mmol/l (95% Cl 0.12-0.78, P = 0.01) more in the controls than in the mineral salt group after adjustment for age, sex and changes in body weight, serum total protein and potassium excretion. Serum HDL-cholesterol was decreased by 0.07 mmol/l in the controls and increased by 0.06 mmol/l in the mineral salt group, yielding a difference of 0.14 mmol/l (95% Cl 0.05-0.22 mmol/l, P = 0.003). The change in HDL/total cholesterol ratio was more favourable in the mineral salt group than in the controls (0.014 and 0.004 units, respectively, P = 0.014). We conclude that long-term moderate sodium restriction does not adversely affect the serum HDL/total cholesterol ratio and is a safe dietary measure for lowering BP.

Objective: To determine the prevalence of risk factors for cardiovascular disease among elderly people., Design: Prospective cohort study., Setting: A district of Rotterdam, the Netherlands., Methods: As a part of the Rotterdam Study information about smoking habits, blood pressure, Quetelet index and serum cholesterol of 7,983 responding persons (78%) (3,105 men and 4,878 women) of 55 years and older was obtained by an interview and physical examination during two visits to a research center., Results: Among men and women there were 29.7% and 16.7% smokers and 60.1% and 25.9% ex-smokers, respectively. Among men the proportion of smokers decreased from 31.0% in the age category 55-59 years to 15.9% in de category > or = 85 years, among women from 28.0% to 2.7%. Systolic blood pressure increased with age in both sexes, while diastolic blood pressure hardly changed. Hypertension (systolic blood pressure 160 mmHg and/or diastolic blood pressure > or = 95 mmHg at a single measurement and/or use of antihypertensive drugs) occurred in 23.3% of men and 28.0% of women. In men, total serum cholesterol decreased gradually with age, whereas in women there was a slight increase up to the category 70-74 years. No evident change in HDL cholesterol with increasing age was observed in men, but in women a decrease was observed until the same level was reached as in men. Thirty-five per cent of men and 49.5% of women had an elevated level of serum cholesterol (> or = 6.5 mmol/l). The prevalence of obesity (Quetelet index > 25 kg/m2) was about 50% in both men and women but was less in the categories from 75 years onwards. Approximately 80% of men and women had at least one risk factor, while in almost half of them two or more risk factors were found., Conclusion: Risk factors for cardiovascular disease are common among elderly people.

Objective: To examine the effect of a reduced sodium and increased potassium and magnesium intake on blood pressure., Design: Randomised double blind placebo controlled trial., Setting: General population of a suburb of Rotterdam., Subjects: 100 men and women between 55 and 75 years of age with untreated mild to moderate hypertension., Interventions: During 24 weeks the intervention group received a mineral salt (sodium: potassium: magnesium 8:6:1) and foods prepared with the mineral salt. Controls received common salt and foods., Main Outcome Measure: Change in blood pressure., Results: Complete follow up was achieved for 97 of the 100 randomised subjects. Systolic blood pressure (mean of measurements at weeks 8, 16, and 24) fell by 7.6 mm Hg (95% confidence interval 4.0 to 11.2) and diastolic blood pressure by 3.3 mm Hg (0.8 to 5.8) in the mineral salt group compared with the controls, with a 28% decrease in urinary sodium excretion and a 22% increase in urinary potassium excretion. Twenty five weeks after the study the difference in blood pressure between the groups was no longer detectable., Conclusion: Replacing common sodium salt by a low sodium, high potassium, high magnesium mineral salt could offer a valuable non-pharmacological approach to lowering blood pressure in older people with mild to moderate hypertension.

Objective: To assess the association between sodium and potassium intake and the rise in blood pressure in childhood., Design: Longitudinal study of a cohort of children with annual measurements during an average follow up period of seven years., Setting: Epidemiological survey of the population of a suburban town in western Netherlands., Subjects: Cohort of 233 children aged 5-17 drawn at random from participants in the population survey., Main Outcome Measures: At least six annual timed overnight urine samples were obtained. The mean 24 hour sodium and potassium excretion during the follow up period was estimated for each participant and the sodium to potassium ratio calculated. Individual slopes of blood pressure over time were calculated by linear regression analysis., Results: No significant association was observed between sodium excretion and the change in blood pressure over time. The mean systolic blood pressure slopes, however, were lower when potassium intake was higher (coefficient of linear regression -0.045 mm Hg/year/mmol; 95% confidence interval -0.069 to -0.020), and the change in systolic pressure was greater when the urinary sodium to potassium ratio was higher (0.356 mm Hg/year/unit; 95% confidence interval 0.069 to 0.642). In relation to potassium this was interpreted as a rise in blood pressure that was on average 1.0 mm Hg (95% confidence interval -1.65 to -0.35) lower in children in the upper part of the distribution of intake compared with those in the lower part. The mean yearly rise in systolic blood pressure for the group as a whole was 1.95 mm Hg. Urinary electrolyte excretion was not associated with diastolic blood pressure., Conclusion: Dietary potassium and the dietary sodium to potassium ratio are related to the rise in blood pressure in childhood and may be important in the early pathogenesis of primary hypertension.