Blood cholesterol : a public health perspective

Changes in total cholesterol levels (TC) were studied using data from three epidemiological studies: about 30,000 men and women aged 37-43 were examined between 1974 and 1980 (CB Project), about 80,000 men aged 33-37 between 1981 and 1986 (RIFOH Project) and 42,000 men and women aged 20-59 from 1987 to 1992 (Monitoring Project on CVD Risk Factors). In men a decline in TC of 6.5% was observed between 1974 and 1992. However, the largest decrease took place between 1981 and 1986 in men in a limited age range (33-37 years), and there were indications that this decrease was not generalizable to other age groups. From 1987 to 1992, a decrease of 7% in HDL cholesterol levels (HDL-C) was observed in men, leading to an increase in the non-HDL-C/HDL-C ratio. In women, no changes in TC and HDL-C were observed.Analyses of data from 36,000 men and women aged 20-59 years showed that between ages 30 and 50 about 19-38% of the gender difference in TC was explained by differences in body mass index (BMI) and cigarette smoking between men and women. After age 50, the higher TC in women compared to men was largely due to the effect of the menopause. The TC increase associated with menopause was 0.45 mmol/l in non-smokers and 0.28 mmol/l in smokers. The difference between a low-risk and a high-risk lifestyle was 0.58 mmol/I for TC and 0.38 mmol/l for HDL-C in men, and 0.40 mmol/l for TC and 0.45 mmol/l for HDL-C in women.Twelve year follow-up of 50,000 men and women aged 30-54 (CB Project) showed that the adjusted relative risk for coronary heart disease (CHD) mortality for the highest compared to the lowest cholesterol quintile was 3.0 (95% CI 1.8-5.1) in men and 3.8 (95% Cl 1.1-13.1) in women. It was estimated that a TC reduction of 0.6 mmol/l was associated with a 20% lower CHD mortality. Low TC was not associated with non-cardiovascular mortality. All-cause mortality was positively related to total cholesterol, with a 60% and 46% higher risk in the highest compared to the lowest TC quintile for men and women respectively.Twenty-five year follow-up of the Seven Countries Study, in which over 12,000 men aged 40-59 at baseline participated, showed that relative risks for CHD mortality were similar in different cultures, but the absolute risks were strikingly different. At a cholesterol level of about 5.4 mmol/l agestandardized CHD mortality rates varied from 4% to 5% in Japan and Mediterranean Southern Europe to 15% in Northern Europe after adjustment for age, smoking and blood pressure. It was concluded that other factors, such as diet, typical for low-risk countries, modify the effect of TC on CHD mortality. In the Seven Countries Study, in non-smokers no association of TC with cancer mortality was observed, while non-cardiovascular/non-cancer mortality was elevated only at TC below 4.15 mmol/l. In smokers, cancer mortality and non-cardiovascular/non-cancer mortality were inversely associated with TC. All- cause mortality showed a J-shaped association with TC in non-smokers (lowest all-cause mortality for TC between 4.15 and 5.15 mmol/l), while all-cause mortality was unrelated to TC in smokers. Absolute mortality rates were higher in smokers than in non-smokers for all endpoints.Lowering the average TC level in the population is concluded to contribute to a reduction in the burden of CHD. Low cholesterol levels are not considered an important public health concern in the Netherlands. Changes in the lipid profile should preferably be achieved by lifestyle interventions such as a diet low in saturated fat and rich in fruits and vegetables, no cigarette smoking, a desirable body mass index (less than 25 kg/m 2) and a physically active lifestyle. Such a lifestyle will not only have a favorable impact on coronary heart disease, but is also compatible with recommendations on the prevention of other chronic diseases such as diabetes and cancer

Colours of fruit and vegetables and 10-year incidence of CHD

The colours of the edible part of fruit and vegetables indicate the presence of specific micronutrients and phytochemicals. The extent to which fruit and vegetable colour groups contribute to CHD protection is unknown. We therefore examined the associations between fruit and vegetables of different colours and their subgroups and 10-year CHD incidence. We used data from a prospective population-based cohort including 20 069 men and women aged 20–65 years who were enrolled between 1993 and 1997. Participants were free of CVD at baseline and completed a validated 178-item FFQ. Hazard ratios (HR) for the association between green, orange/yellow, red/purple, white fruit and vegetables and their subgroups with CHD were calculated using multivariable Cox proportional hazards models. During 10 years of follow-up, 245 incident cases of CHD were documented. For each 25 g/d increase in the intake of the sum of all four colours of fruit and vegetables, a borderline significant association with incident CHD was found (HR 0·98; 95 % CI 0·97, 1·01). No clear associations were found for the colour groups separately. However, each 25 g/d increase in the intake of deep orange fruit and vegetables was inversely associated with CHD (HR 0·74; 95 % CI 0·55, 1·00). Carrots, their largest contributor (60 %), were associated with a 32 % lower risk of CHD (HR 0·68; 95 % CI 0·48, 0·98). In conclusion, though no clear associations were found for the four colour groups with CHD, a higher intake of deep orange fruit and vegetables and especially carrots may protect against CH

Linoleic acid intake, plasma cholesterol and 10-year incidence of CHD in 20.000 middle-aged men and women in the Netherlands

We studied the associations of a difference in linoleic acid or carbohydrate intake with plasma cholesterol levels and risk of CHD in a prospective cohort study in the Netherlands. Data on diet (FFQ) and plasma total and HDL-cholesterol were available at baseline (1993–7) of 20 069 men and women, aged 20–65 years, who were initially free of CVD. Incidence of CHD was assessed through linkage with mortality and morbidity registers. During an average of 10 years of follow-up, 280 CHD events occurred. The intake of linoleic acid ranged from 3·6 to 8·0 % of energy (en%), whereas carbohydrate intake ranged from 47·6 to 42·5 en% across quintiles of linoleic acid intake. Linoleic acid intake was inversely associated with total cholesterol and HDL-cholesterol in women but not in men. Linoleic acid intake was not associated with the ratio of total to HDL-cholesterol. No association was observed between linoleic acid intake and CHD incidence, with hazard ratios varying between 0·83 and 1·00 (all P>0·05) compared to the bottom quintile. We conclude that a 4–5 en% difference in linoleic acid or carbohydrate intake did not translate into either a different ratio of total to HDL-cholesterol or a different CHD incidenc

Spectrally Similar Incommensurable 3-Manifolds

Reid has asked whether hyperbolic manifolds with the same geodesic length spectrum must be commensurable. Building toward a negative answer to this question, we construct examples of hyperbolic 3–manifolds that share an arbitrarily large portion of the length spectrum but are not commensurable. More precisely, for every n ≫ 0, we construct a pair of incommensurable hyperbolic 3–manifolds Nn and Nµn whose volume is approximately n and whose length spectra agree up to length n. Both Nn and Nµn are built by gluing two standard submanifolds along a complicated pseudo-Anosov map, ensuring that these manifolds have a very thick collar about an essential surface. The two gluing maps differ by a hyper-elliptic involution along this surface. Our proof also involves a new commensurability criterion based on pairs of pants

Sources of dietary protein and risk of hypertension in a general Dutch population

Evidence suggests a small beneficial effect of dietary protein on blood pressure (BP), especially for plant protein. We examined the relationship between several types of dietary protein (total, plant, animal, dairy, meat and grain) and the risk of hypertension in a general population of 3588 Dutch adults, aged 26–65 years, who were free of hypertension at baseline. Measurements were done at baseline and after 5 and 10 years of follow-up. Hazard ratios (HR), with 95 % CI, for incident hypertension were obtained in tertiles of energy-adjusted protein, using time-dependent Cox regression models. Models were adjusted for age, sex, BMI, education, smoking, baseline systolic BP, dietary confounders and protein from other sources (if applicable). Mean BP was 118/76 mmHg at baseline. Protein intake was 85 (sd 22) g/d (approximately 15 % of energy) with 62 % originating from animal sources. The main sources of protein were dairy products (28 %), meat (24 %) and grain (19 %). During the follow-up, 1568 new cases of hypertension were identified (44 % of the participants). Energy-adjusted intake of total protein, plant protein and animal protein was not significantly associated with hypertension risk (all HR approximately 1·00, P>0·60). Protein from grain showed a significant inverse association with incident hypertension, with a HR of 0·85 (95 % CI 0·73, 1·00, Ptrend = 0·04) for the upper tertile ( = 18 g/d) v. the lower tertile ( <14 g/d), whereas dairy protein and meat protein were not associated with incident hypertension. In conclusion, higher intake of grain protein may contribute to the prevention of hypertension, which warrants confirmation in other population-based studies and randomised controlled trials

Tailoring the Implementation of New Biomarkers Based on Their Added Predictive Value in Subgroups of Individuals

Background\ud The value of new biomarkers or imaging tests, when added to a prediction model, is currently evaluated using reclassification measures, such as the net reclassification improvement (NRI). However, these measures only provide an estimate of improved reclassification at population level. We present a straightforward approach to characterize subgroups of reclassified individuals in order to tailor implementation of a new prediction model to individuals expected to benefit from it.\ud \ud Methods\ud In a large Dutch population cohort (n = 21,992) we classified individuals to low (<5%) and high (≥5%) fatal cardiovascular disease risk by the Framingham risk score (FRS) and reclassified them based on the systematic coronary risk evaluation (SCORE). Subsequently, we characterized the reclassified individuals and, in case of heterogeneity, applied cluster analysis to identify and characterize subgroups. These characterizations were used to select individuals expected to benefit from implementation of SCORE.\ud \ud Results\ud Reclassification after applying SCORE in all individuals resulted in an NRI of 5.00% (95% CI [-0.53%; 11.50%]) within the events, 0.06% (95% CI [-0.08%; 0.22%]) within the nonevents, and a total NRI of 0.051 (95% CI [-0.004; 0.116]). Among the correctly downward reclassified individuals cluster analysis identified three subgroups. Using the characterizations of the typically correctly reclassified individuals, implementing SCORE only in individuals expected to benefit (n = 2,707,12.3%) improved the NRI to 5.32% (95% CI [-0.13%; 12.06%]) within the events, 0.24% (95% CI [0.10%; 0.36%]) within the nonevents, and a total NRI of 0.055 (95% CI [0.001; 0.123]). Overall, the risk levels for individuals reclassified by tailored implementation of SCORE were more accurate.\ud \ud Discussion\ud In our empirical example the presented approach successfully characterized subgroups of reclassified individuals that could be used to improve reclassification and reduce implementation burden. In particular when newly added biomarkers or imaging tests are costly or burdensome such a tailored implementation strategy may save resources and improve (cost-)effectivenes

Serum cholesterol is a risk factor for myocardial infarction in elderly men and women: The Rotterdam Study

Objective. To investigate the associations of serum total and HDL cholesterol with the risk of myocardial infarction in men and women of 55 years and over. Design. The Rotterdam Study is a population-based prospective cohort study. In total 2453 men and 3553 women of 55 years and older were included in this study. The mean duration of follow-up was 4 years. Main outcome measures. Relative risks were estimated with Cox's proportional- hazard analysis. Cholesterol was analysed as a continuous variable and in sex-specific quartiles. Results. In subjects aged 55 years and older the relative risk of myocardial infarction was 1.9 in men (95% confidence interval 1.1-3.3) and 3.2 in women (1.5-6.4) in the highest compared to the lowest serum total cholesterol quartile (Q4 vs. Q1). In men and women of 70 years and older, total cholesterol remained an important risk factor for myocardial infarction (Q4 vs. Q1 relative risk 3.2; 1.3-7.7 and 2.9; 1.3- 6.6, respectively). For HDL cholesterol, the relative risk in the highest compared to the lowest quartile (Q4 vs. Q1) was 0.5 in men (0.3-0.9) and 0.4 in women (0.2-0.9). HDL cholesterol was a weaker predictor in men after the age of 70 (Q4 vs. Q1 0.8; 0.3-2.1). In women of 70 years and older the relative risk was also not significant (Q4 vs. Q1 0.6; 0.3-1.3), although the trend over the quartiles was still significant. Conclusion. Serum total cholesterol remains an important risk factor for myocardial infarction in men and women aged 70 years and older, whilst HDL cholesterol at older age remains important in women only

Variety in fruit and vegetable consumption and 10-year incidence of CHD and stroke

Objective: Consuming a variety of fruit and vegetables provides many different micronutrients and bioactive compounds. Whether this contributes to the beneficial association between fruit and vegetables and incident CHD and stroke is unknown. Design: Prospective population-based cohort study. Setting: The Netherlands. Subjects: Men and women (n 20 069) aged 20-65 years. Participants completed a validated 178-item FFQ, including nine fruit and thirteen vegetable items. Variety in fruit and vegetables was defined as the sum of different items consumed at least once per 2 weeks over the previous year. Hazard ratios (HR) for variety in relation to incident CHD and stroke were calculated using multivariable Cox proportional hazards models additionally adjusted for quantity of fruit and vegetables. Results: Variety and quantity in fruit and vegetables were highly correlated (r=0.81). Variety was not associated with total energy intake (r=-0.01) and positively associated with nutrient intakes, particularly vitamin C (r=0.70). During 10 years of follow-up, 245 cases of CHD and 233 cases of stroke occurred. Variety in vegetables (HR per 2 items = 1.05; 95% CI 0.94, 1.17) and in fruit (HR per 2 items = 1.00; 95% CI 0.87, 1.15) were not related to incident CHD. Variety in vegetables (HR per 2 items = 0.93; 95% CI 0.83, 1.04) and in fruit (HR per 2 items = 1.03; 95% CI 0.89, 1.18) were also not related to incident stroke. Conclusions: More variety in fruit and vegetable consumption was associated with higher intakes of fruit and vegetables and micronutrients. Independently of quantity, variety in fruit and vegetables was related neither to incident CHD nor to incident stroke

Hypertension is frequently present in patients with reflux esophagitis or Barrett's esophagus but not in those with non-ulcer dyspepsia

Background: Elevated mortality due to cardiovascular disease has been reported for patients with Barrett's esophagus (BE). We compared the prevalence of risk factors for cardiovascular disease in patients with BE, reflux esophagitis (RE), and non-ulcer dyspepsia (NUD) with that of the general population. Methods: Patients with upper gastrointestinal complaints and BE, RE, or NUD were compared with a matched cohort from the general population using a questionnaire and blood pressure and cholesterol measurements. Results: Hypertension occurred more frequently in patients with BE (odds ratio 5.1, P<0.0001) and RE (odds ratio 3.8, P<0.001), but not in those with NUD. Serum total cholesterol was higher in BE (P=0.02) and borderline in RE (P=0.06) but not in NUD. Mean HDL cholesterol levels, body mass index, and smoking did not differ. Conclusions: This study suggests that BE and RE found at diagnostic endoscopy are associated with an increased prevalence of hypertension and a higher total cholesterol level than in the general population. If so, this would explain the increased mortality during the follow-up of BE patients, and it should be taken into account when designing or evaluating follow-up studies of BE

Near normal HbA1c with stable glucose homeostasis: the ultimate target/aim of diabetes therapy

Background: The long-term longitudinal evidence for a relation between coffee intake and hypertension is relatively scarce. Objective: The objective was to assess whether coffee intake is associated with the incidence of hypertension. Design: This study was conducted on a cohort of 2985 men and 3383 women who had a baseline visit and follow-up visits after 6 and 11 y. Baseline coffee intake was ascertained with questionnaires and categorized into 0, &gt; 0-3, &gt; 3-6, and &gt; 6 cups/d. Hypertension was defined as a mean systolic blood pressure (SBP) &gt;= 140 mm Hg over both follow-up measurements, a mean diastolic blood pressure (DBP) &gt;= 90 mm Hg over both follow-up measurements, or the use of antihypertensive medication at any follow-up measurement. Results: Coffee abstainers at baseline had a lower risk of hypertension than did those with a coffee intake of &gt; 0-3 cups/d [odds ratio (OR): 0.54; 95% CI: 0.31, 0.92]. Women who drank &gt; 6 cups/d had a lower risk than did women who drank &gt; 0-3 cups/d (OR: 0.67; 95% CI: 0.46, 0.98). Subjects aged &gt;= 39 y at baseline had 0.35 mm Hg (95% CI: -0.59, -0.11 mm Hg) lower SBP per cup intake/d and 0.11 mm Hg lower DBP (95% CI: -0.26, 0.03 mm Hg) than did those aged &lt;39 y at baseline, although the difference in DBP was not statistically significant. Conclusions: Coffee abstinence is associated with a lower hypertension risk than is low coffee consumption. An inverse U-shaped relation between coffee intake and risk of hypertension was observed in the women