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Biomedical subjects

Diederick E Grobbee

Publications and source records attributed to Diederick E Grobbee.

At least 19 recordsLinked to original sources

Transient caloric restriction and cancer risk (The Netherlands).

Over the past century, many animal experiments have shown that caloric restriction can reduce the risk of cancer, a finding that proved to be highly reproducible. Many papers have been published on its potential for human health, but until know little evidence is available on its actual effects in humans. In Utrecht, The Netherlands, we have been investigating the effects of the 1944-1945 Dutch famine on breast cancer risk factors and breast cancer risk, and paradoxically the relatively short-term famine seemed to be related to increased breast cancer risk in later life. One of the differences between the famine situation and the large body of evidence from animal experiments is the duration of caloric restriction. Almost all animal experiments investigated sustained caloric restriction and information on the effects of short-term transient caloric restriction is very scarce. A search in the literature identified some animal experiments on short-term transient caloric restriction and these seemed to be at least supportive to the famine findings. Because caloric restriction in humans for preventive health measures would be mostly short-term, it is important to extend animal research on short-term caloric restriction.

Animals↗

Innate handedness and disease-specific mortality in women.

BACKGROUND: Left-handedness has been reported to be associated with reduced life expectancy, but the evidence is far from conclusive. METHODS: We studied the association between innate handedness and total mortality, as well as cause-specific mortality, in a cohort of 12,178 middle-aged Dutch women who were followed for almost 13 years. The relation between handedness and mortality was analyzed using Cox regression in a case-cohort approach, in which a random sample of 1500 women was used to represent person-years under observation for the entire cohort. RESULTS: During a median follow-up of 12.6 years, 252 women died. Hazard ratios comparing left-handed women with other women were 1.4 for all-cause mortality (95% confidence interval = 0.9-2.0), 1.7 for total cancer mortality (1.0-2.7), 2.0 for breast cancer mortality (0.8-4.6), 4.6 for colorectal cancer mortality (1.5-14.3), 1.3 mortality from diseases of the circulatory system (0.5-3.3), and 3.7 for cerebrovascular mortality (1.1-12.1), after adjusting for potential confounders (socioeconomic status, age, body mass index, and cigarette smoking status at study recruitment). CONCLUSIONS: Left-handedness is associated with higher mortality in women.

Adult↗

Common genetic variations in CCK, leptin, and leptin receptor genes are associated with specific human eating patterns.

Obesity has a heritable component; however, the heterogeneity of obesity complicates dissection of its genetic background. In this study, we therefore focused on eating patterns as specific traits within obesity. These traits have a heritable component; genes associated with a specific eating pattern have not yet been reported at the population level. In this study, we determined whether genetic variations in cholecystokinin (CCK) and leptin genes underlie specific eating patterns. We selected obese individuals showing extreme snacking behavior or use of excessive portion sizes from a large population-based sample (n = 17,357) from the Prospect-EPIC (European Prospective Study into Cancer and Nutrition) study. Using allele-specific PCRs, we tested several single nucleotide polymorphisms in the candidate genes and performed haplotype analysis. Obese carriers of common allelic variations in leptin or the leptin receptor gene had an increased risk to display extreme snacking behavior. In contrast, obese carriers of common allelic variations in CCK had an increased risk to eating increased meal sizes. In conclusion, we identified common allelic variants specifically associated with distinctly different eating patterns, namely extreme snacking behavior or excessive portion size.

Aged↗

Improved risk adjustment for comparison of surgical site infection rates.

OBJECTIVE: To develop prognostic models for improved risk adjustment in surgical site infection surveillance for 5 surgical procedures and to compare these models with the National Nosocomial Infection Surveillance system (NNIS) risk index. DESIGN: In a multicenter cohort study, prospective assessment of surgical site infection and risk factors was performed from 1996 to 2000. In addition, risk factors abstracted from patient files, available in a national medical register, were used. The c-index was used to measure the ability of procedure-specific logistic regression models to predict surgical site infection and to compare these models with models based on the NNIS risk index. A c-index of 0.5 indicates no predictive power, and 1.0 indicates perfect predictive power. SETTING: Sixty-two acute care hospitals in the Dutch national surveillance network for nosocomial infections. PARTICIPANTS: Patients who underwent 1 of 5 procedures for which the predictive ability of the NNIS risk index was moderate: reconstruction of the aorta (n=875), femoropopliteal or femorotibial bypass (n=641), colectomy (n=1,142), primary total hip prosthesis (n=13,770), and cesarean section (n=2,962). RESULTS: The predictive power of the new model versus the NNIS index was 0.75 versus 0.62 for reconstruction of the aorta (P<.01), 0.78 versus 0.58 for femoropopliteal or femorotibial bypass (P<.001), 0.69 versus 0.62 for colectomy (P<.001), 0.64 versus 0.56 for primary total hip prosthesis arthroplasty (P<.001), and 0.70 versus 0.54 for cesarean section (P<.001). CONCLUSION: Data available from hospital information systems can be used to develop models that are better at predicting the risk of surgical site infection than the NNIS risk index. Additional data collection may be indicated for certain procedures--for example, total hip prosthesis arthroplasty.

Aged↗

Acetylsalicylic acid as an adjuvant therapy for schizophrenia.

BACKGROUND: Findings from both epidemiological and basic research point to the possibility that NSAIDS impede the deterioration in schizophrenia. METHODS: To study the efficacy of acetylsalicylic acid we will perform a randomized placebo controlled double-blind add-on trial of 80 inpatients and outpatients with schizophrenia, schizophreniform or schizoaffective disorder. Patients will be 1:1 randomized to either 3 months 1000 mg acetylsalicylic acid per day or 3 months placebo, in addition to their regular antipsychotic treatment. All patients will receive pantoprazole treatment for gastroprotection. The outcomes of this study are 3-month change in psychotic and negative symptom severity, cognitive function, and several immunological parameters. This trial may (1) yield a new (adjuvant) therapy for schizophrenia and (2) add to the knowledge on the pathogenesis of this major psychiatric disorder.

Journal Article↗

Vitamin K intake and calcifications in breast arteries.

OBJECTIVES: Vitamin K is an important co-factor in the production of proteins that inhibit vascular calcification. A low dietary Vitamin K intake has been associated with aortic and coronary calcifications and an elevated cardiovascular risk. Calcifications in the arteries of the breasts have also been associated with cardiovascular risk, but whether there is a relation with a low Vitamin K intake has not yet been studied. METHODS: We conducted a cross-sectional study among 1689 women, aged 49-70 years. Dietary Vitamins K1 and K2 intake was calculated from a validated food frequency questionnaire. Breast arterial calcifications (BAC) were assessed on standard screening mammograms by two independent radiologists. With a general linear model mean Vitamins K1, K2 and Vitamin K2 subtypes were calculated for women with BAC and without, adjusted for age, smoking, diabetes, intake of saturated fat, mono-unsaturated fat, poly-unsaturated fat and protein- and calcium-intake. RESULTS: BAC was less common in the highest (9%) quartile of Vitamin K2 intake, compared to the lowest (13%) (OR 0.7, 95% CI 0.5-1.1) and not different across quartiles of Vitamin K1 intake. Mean Vitamin K2 levels and mean levels of Vitamin K2 subtypes MK-5 through MK-10 were lower in the participants with BAC (p=0.01) compared to participants without BAC. However, after adjustment for aging, smoking, diabetes and dietary factors the association of mean Vitamin K2 intake with BAC was no longer significant. CONCLUSION: Calcifications in breast arteries are not associated with a lower dietary intake of Vitamin K.

Aged↗

Rationale and design of the AdRem study: evaluating the effects of blood pressure lowering and intensive glucose control on vascular retinal disorders in patients with type 2 diabetes mellitus.

The ADVANCE Retinal Measurements (AdRem) Study is a large intervention study evaluating the effects of target driven intensive glucose control and placebo controlled blood pressure lowering on retinal vascular changes. AdRem is a sub-study of the ADVANCE Study (Action in Diabetes and Vascular disease), a 2x2 factorial randomized controlled trial with an ACE inhibitor-diuretic combination (perindopril-indapamide) and a gliclazide MR-based regimen in patients with type 2 diabetes mellitus. The AdRem study is based on seven-field stereoscopic retinal photographs of both eyes. These are taken within 3 months after randomization in ADVANCE (baseline), at the biennial and at the final visit. The primary outcome is progression of two or more steps in ETDRS classification. Secondary outcomes include progression of retinal vascular lesions and distortion of retinal vascular geometry. Retinal photographs are made on film and digitized at a central laboratory. The AdRem study uses fully digitized quality control and grading. Between August 2002 and January 2004 1978 patients were included in the AdRem study, from 39 centers in 14 countries. Approximately 85% comply with the strict AdRem quality requirements. Publication of the results is expected in early 2008. The AdRem study is designed to provide reliable evidence on the effects of intensive glucose control and blood pressure lowering on both diabetic retinopathy and abnormalities of retinal vasculature in patients with type 2 diabetes mellitus.

Antihypertensive Agents↗

Short- and long-term prognosis after acute myocardial infarction in men versus women.

The prevailing view is that women have a higher early mortality after acute myocardial infarction (AMI) than men, but several studies have shown no differences. Further, long-term differences have not been addressed widely. The present study examined gender differences in short- and long-term prognoses after AMI in The Netherlands. A nationwide cohort of 21,565 patients with a first hospitalized AMI in 1995 was identified through linkage of the National Hospital Discharge Register and the population register. Crude short- and long-term mortalities were significantly higher in women than in men (28-day hazard ratio [HR] 1.70, 95% confidence interval [CI] 1.58 to 1.82; 5-year HR 1.52, 95% CI 1.46 to 1.59). After adjustment for age, the risk difference was attenuated at 28 days and even reversed at 5 years in favor of women (28-day HR 1.11, 95% CI 1.03 to 1.20; 5-year HR 0.94, 95% CI 0.90 to 0.99). When differences in other covariates were also taken into account, the risk differences remained virtually the same. To account for differences in reperfusion procedures, we repeated the analyses in 1,176 patients who underwent acute reperfusion therapy (angioplasty/thrombolysis). Comparable, but not statistically significant, gender differences were observed (28-day HR 1.06, 95% CI 0.65 to 1.74; 5-year HR 0.82, 95% CI 0.62 to 1.08). In conclusion, our findings in an unselected cohort covering a complete nation indicate that the worse short- and long-term prognoses after an AMI in women compared with men may largely be explained by differences in age, whereas differences in co-morbidity, origin, infarct location, and reperfusion therapy seem to contribute little.

Adult↗

Comparison of routine care self-reported and biometrical data on hypertension and diabetes: results of the Utrecht Health Project.

BACKGROUND: Information on the prevalence of diseases is commonly gathered by questionnaires. Although the method is relatively inexpensive and efficient as opposed to physical examinations, the validity of the information collected is often questioned. The objective of this study was to assess the value of biometrical data complementary to self-reported questionnaire information for estimating the prevalence of hypertension and diabetes in the population at large and to examine factors that affect the accuracy of self-reporting. METHODS: Baseline data of 4950 adult participants of the Utrecht Health Project, a community-based prospective cohort study, were used to calculate sensitivity and specificity of self-reported hypertension and diabetes with the results of blood pressure measurements and blood glucose levels, corrected for current medication use, as the reference standard. Multivariate logistic regression analysis was performed to determine which participants' characteristics independently predicted the accuracy of self-reports. RESULTS: Overall sensitivity was 34.5% for self-reported data on hypertension and 58.9% for diabetes, while overall specificity was high for both conditions (96.4 and 99.4%, respectively). The agreement between self-reported and biometrical data was higher for diabetes than for hypertension and varied per subgroup. CONCLUSIONS: The use of self-reported data to estimate the prevalence of hypertension and diabetes may lead to underestimated prevalence estimates and biased associations with risk factors due to differential misclassification. Adding biometrical measurements to self-reported questionnaire information will assure the validity of the data. The magnitude of the additional value of biometrical data depends on the condition studied and the characteristics of the population under investigation.

Adolescent↗

Double blind randomized placebo-controlled trial on the effects of testosterone supplementation in elderly men with moderate to low testosterone levels: design and baseline characteristics [ISRCTN23688581].

In ageing men testosterone levels decline, while cognitive function, muscle and bone mass, sexual hair growth, libido and sexual activity decline and the risk of cardiovascular diseases increase. We set up a double-blind, randomized placebo-controlled trial to investigate the effects of testosterone supplementation on functional mobility, quality of life, body composition, cognitive function, vascular function and risk factors, and bone mineral density in older hypogonadal men. We recruited 237 men with serum testosterone levels below 13.7 nmol/L and ages 60-80 years. They were randomized to either four capsules of 40 mg testosterone undecanoate (TU) or placebo daily for 26 weeks. Primary endpoints are functional mobility and quality of life. Secondary endpoints are body composition, cognitive function, aortic stiffness and cardiovascular risk factors and bone mineral density. Effects on prostate, liver and hematological parameters will be studied with respect to safety. Measure of effect will be the difference in change from baseline visit to final visit between TU and placebo. We will study whether the effect of TU differs across subgroups of baseline waist girth (< 100 cm vs. > or = 100 cm; testosterone level (< 12 versus > or = 12 nmol/L), age (< median versus > or = median), and level of outcome under study (< median versus > or = median). At baseline, mean age, BMI and testosterone levels were 67 years, 27 kg/m2 and 10.72 nmol/L, respectively.

Journal Article↗

Carotid intima-media thickness and the risk of new vascular events in patients with manifest atherosclerotic disease: the SMART study.

AIMS: Carotid intima-media thickness (CIMT) is an independent predictor of vascular events in the general population. Currently, little is known about the relationship between CIMT and new vascular events in patients with manifest arterial disease. We aimed to assess the strength of this relationship. METHODS AND RESULTS: The study was performed in the first consecutive 2374 patients with manifest arterial disease enrolled in the cohort study SMART (Second Manifestations of ARTerial disease), a cohort study among patients with manifest arterial disease or cardiovascular risk factors. Common CIMT was measured at baseline in both carotid arteries. Vascular events were vascular death, non-fatal myocardial infarction, or stroke, whichever occurred first. Adjusted for age and sex, an increase in common CIMT of 1 SD ( approximately 0.32 mm) was associated with the occurrence of vascular events [hazard ratio (HR) 1.18; 95% confidence interval (95% CI) 1.04-1.32]. Increasing CIMT was most strongly related to ischaemic stroke incidence (HR 1.35; 95% CI 1.16-1.59). Results were similar in the 2177 patients without large common carotid plaques (CIMT <2 mm at all measurements sites). The findings were similar after additional adjustment for risk factors of CIMT and vascular risk. CONCLUSION: Common CIMT is associated with the occurrence of new vascular events, mostly for ischaemic stroke, in patients with manifest arterial disease. This relation does not appear to depend on the presence of plaques.

Adolescent↗

Effects of dehydroepiandrosterone and atamestane supplementation on frailty in elderly men.

BACKGROUND: It has been suggested that the age-related decline of androgens in men plays a distinct role in the development of several aspects of frailty. Therefore, hormone replacement might improve the course of frailty by increasing lean body mass and muscle strength, decreasing fat mass, and improving the subjective quality of life. OBJECTIVE: The objective of the study was to assess whether hormone replacement with dehydroepiandrosterone (DHEA) and/or atamestane might improve the course of frailty. DESIGN: This was a double-blind, randomized, controlled trial. SETTING: The study was conducted in the general community. PARTICIPANTS: Participants included 100 nonhospitalized, nondiseased, independently living men, aged 70 yr and over with low scores on strength tests. Seventeen participants did not complete the trial. INTERVENTION: Subjects were randomly assigned to one of four intervention arms: atamestane (100 mg/d) and placebo, DHEA (50 mg/d) and placebo, a combination of atamestane (100 mg/d) and DHEA (50 mg/d), or two placebo tablets for 36 wk. MAIN OUTCOME MEASURES: Physical frailty was measured by means of a specific test battery, including isometric grip strength, leg extensor power, and physical performance. RESULTS: The randomization was successful, and 83 (83%) men completed the intervention. There were no differences between the treatment arms and placebo group in any of the outcome measurements after intervention. CONCLUSIONS: The results of this double-blind, randomized trial do not support the hypothesis that hormone replacement with DHEA and/or atamestane might improve the course of frailty.

Activities of Daily Living↗

Calculation of bioavailable and free testosterone in men: a comparison of 5 published algorithms.

BACKGROUND: Estimation of serum concentrations of free testosterone (FT) and bioavailable testosterone (bioT) by calculation is an inexpensive and uncomplicated method. We compared results obtained with 5 different algorithms. METHODS: We used 5 different published algorithms [described by Sodergard et al. (bioTS and FTS), Vermeulen et al. (bioTV and FTV), Emadi-Konjin et al. (bioTE), Morris et al. (bioTM), and Ly et al. (FTL)] to estimate bioT and FT concentrations in samples obtained from 399 independently living men (ages 40-80 years) participating in a cross-sectional, single-center study. RESULTS: Mean bioT was highest for bioTS (10.4 nmol/L) and lowest for bioT(E) (3.87 nmol/L). Mean FT was highest for FTS (0.41 nmol/L), followed by FTV (0.35 nmol/L), and FTL (0.29 nmol/L). For bioT concentrations, the Pearson correlation coefficient was highest for the association between bioTS and bioTV (r = 0.98) and lowest between bioTM and bioTE (r = 0.66). FTL was significantly associated with both FTS (r = 0.96) and FTV (r = 0.88). The Pearson correlation coefficient for the association between FTL and bioTM almost reached 1.0. Bland-Altman analysis showed large differences between the results of different algorithms. BioTM, bioTE, bioTV, and FTL were all significantly associated with sex hormone binding globulin (SHBG) concentrations. CONCLUSION: Algorithms to calculate FT and bioT must be revalidated in the local setting, otherwise over- or underestimation of FT and bioT concentrations can occur. Additionally, confounding of the results by SHBG concentrations may be introduced.

Adult↗

Anthropometric measures, endogenous sex steroids and breast cancer risk in postmenopausal women: a study within the EPIC cohort.

In a large case-control study on breast cancer risk and serum hormone concentrations, nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, we examined to what extent the relationship of excess body weight with breast cancer risk may be explained by changes in sex steroids. Height, weight, waist and hip circumferences, and serum measurements of testosterone [T], androstenedione [Delta4], dehydroepiandrosterone sulphate [DHEAS], estradiol [E2], estrone [E1] and sex-hormone binding globulin [SHBG] were available for 613 breast cancer cases, and 1,139 matched controls, who were all menopausal at the time of blood donation. Free T [fT] and free E2 [fE2] were calculated using mass action equations. Breast cancer risk was related to body mass index (BMI) (RR = 1.11 [0.99-1.25], per 5 kg/m2 increase in BMI), and waist (RR = 1.12 [1.02-1.24], per 10 cm increase) and hip circumferences (RR = 1.14 [1.02-1.27], per 10 cm increase). The increase in breast cancer risk associated with adiposity was substantially reduced after adjustment for any estrogens, especially for fE2 (from 1.11 [0.99-1.25] to 0.99 [0.87-1.12], from 1.12 [1.02-1.24] to 1.02 [0.92-1.14] and from 1.14 [1.02-1.27] to 1.05 [0.93-1.18] for BMI, waist and hip circumferences, respectively). A modest attenuation in excess risk was observed after adjustment for fT, but the remaining androgens had little effect on the association of body adiposity with breast cancer. Our data indicate that the relationship of adiposity with breast cancer in postmenopausal women could be partially explained by the increases in endogenous estrogens, and by a decrease in levels of SHBG.

Adiposity↗

Coronary collateral circulation: the effects of smoking and alcohol.

OBJECTIVE: The presence or absence of coronary collaterals is of vital importance during acute ischemia. Smoking and alcohol have been suggested to play a role, but data are scarce. We examined the extent to which smoking and alcohol use affect the presence of coronary collateral circulation. METHODS: Cross-sectional study in 242 patients, admitted for elective PTCA. Smoking was defined as past or current. Pack years were calculated and categorized into never-smokers (reference-category): <10, 10-19, 20-29, and >or=30 pack years. Alcohol consumption was defined as past or current, and categorized into never-users (reference-category): <1, 1-10, 11-20, and >or=21 units per week (UPW). Collaterals were graded with Rentrop's classification. Coronary collateral presence was defined as Rentrop-grade >or=1. RESULTS: Current smoking (odds ratio (OR) 4.17; 95% confidence interval (CI) 1.79-9.71) was positively associated, while pack years of smoking was not related. Current alcohol intake showed a J-shaped tendency with coronary collateral presence, while past moderate alcohol consumption was inversely associated (OR 0.19; 95% CI 0.04-0.98). CONCLUSIONS: Smoking and (to some extent) alcohol use are associated with collateral presence. The results support the view that life-style factors may affect the formation of coronary collaterals in patients with ischemic cardiac disease.

Aged↗

Determinants and prognostic significance of collaterals in patients undergoing coronary revascularization.

There is evidence that coronary collaterals improve the prognosis in patients with acute myocardial infarction (MI). However, there is limited clinical information on the protective role of collaterals in patients with stable coronary artery disease. This information may help risk stratification and the development of novel therapies, such as arteriogenesis and angiogenesis. The relation between collaterals and cardiac death or MI at 1 year after coronary revascularization was studied in 561 patients who were enrolled in a randomized study that compared stent implantation with bypass grafting. Collaterals were assessed on an angiogram using Rentrop's classification and considered present with a Rentrop grade >1. Unadjusted and adjusted odds ratios for cardiac death or MI at 1 year were calculated using univariate and multivariate regression analyses. In addition, determinants of collaterals were assessed using univariate and multivariate analyses. Collaterals were present in 176 patients (31%). The adjusted odds ratio of cardiac death or infarction was 0.18 (95% confidence interval 0.04 to 0.78) in the presence of collaterals. Independent determinants of collaterals were age (odds ratio 0.97, 95% confidence interval 0.95 to 0.99), multivessel disease (odds ratio 1.60, 95% confidence interval 1.02 to 2.51), impaired ventricular function (odds ratio 1.85, 95% confidence interval 1.04 to 3.29), type C lesion (odds ratio 3.72, 95% confidence interval 2.33 to 5.95), and stenosis severity >90% (odds ratio 9.08, 95% confidence interval 4.65 to 17.73). In conclusion, in patients with a low risk profile, the presence of collaterals protects against cardiac death and MI at 1 year after coronary revascularization. Variables that reflect the duration and severity of the atherosclerotic and ischemic burden determine their presence.

Angioplasty, Balloon, Coronary↗

Increased occurrence of left-handedness after severe childhood bacterial meningitis: support for the pathological left-handedness hypothesis.

The hypothesis that brain damage during infancy causes pathological left-handedness was tested by assessing handedness in 182 survivors of childhood non-Hemophilus influenza type b bacterial meningitis in the Netherlands (mean age of 9.7 years). These children were selected randomly after clustering them into those with or without parental report on academic and behavioural problems. Medical records were obtained from the hospitals, while handedness and neurodevelopmental outcome were assessed at school age. Logistic regression analysis was used to study the relationship between a severity score of bacterial meningitis and handedness. Fifteen percent were left-handed. Severity of childhood bacterial meningitis was related to left-handedness (Odds ratio (OR) 6.2, 95% confidence interval (CI) 2.0-18.6 for those with a total severity score above the median as compared to those below). Compared to non-left-handed children, left-handed children had lower IQ (mean difference -6.6, 95% CI -12 to -1.2), tended to have lower vocabulary scores on WISC-r (-1.0, -2.1 to 0), and lower Beery scores on visual-motor integration (-4.9, -10.1 to 0.4). Left-handed children also tended to have more combined academic and behavioural limitations (OR 2.7, 95% CI 0.9-8.6), lower manual speed of the dominant hand (mean difference -9 taps, p < 0.05) and better manual steadiness in the non-dominant hand (mean difference of contact's time -2.7 s, p < 0.05). Left-handed post-meningitic children generally have worse neurodevelopmental outcome than non-left-handed survivors. Our results support the role of early life brain damage in left-handedness.

Child↗

Heart disease risk determines menopausal age rather than the reverse.

OBJECTIVES: The purpose of this study was to investigate whether a harmful cardiovascular risk profile accelerates menopause. BACKGROUND: Women with an early menopause are at an increased risk of cardiovascular disease. Although increased cardiovascular risk has been proposed as consequence of menopause, the alternative hypothesis, that increased premenopausal cardiovascular risk promotes early menopause, needs to be examined. METHODS: We used data from the Framingham Heart Study cohort. This study started in 1948 and has followed up participants biennially since then. Women who were premenopausal at study entry and who reached natural menopause after at least two examination rounds were included in the study (n = 695). Premenopausal age-independent levels of serum total cholesterol, relative weight, blood pressure, and Framingham risk score were determined, as well as premenopausal changes in cholesterol, body weight, and blood pressure. RESULTS: A higher premenopausal serum total cholesterol level was statistically significantly associated with an earlier age at menopause, as were increases in total serum cholesterol, relative weight, and blood pressure in the premenopausal period. A decrease in total serum cholesterol during premenopause was statistically significantly associated with later age at menopause. Decreasing blood pressure was associated with a later menopausal age, but this association was not statistically significant. A decrease in relative weight was associated with a significant earlier age at menopause. Each 1% higher premenopausal Framingham risk score was associated with a decrease in menopausal age of 1.8 years (95% confidence interval -2.72 to -0.92). CONCLUSIONS: The findings support the view that heart disease risk determines age at menopause. This offers a novel explanation for the inconsistent findings on cardiovascular disease rate and its relationship to menopausal age and effects of hormone replacement therapy.

Adult↗