Showing papers by "Diederick E. Grobbee published in 2007"

Effect of Rosuvastatin on Progression of Carotid Intima-Media Thickness in Low-Risk Individuals With Subclinical Atherosclerosis: The METEOR Trial

Abstract: ContextAtherosclerosis is often advanced before symptoms appear and it is not clear whether treatment is beneficial in middle-aged individuals with a low Framingham risk score (FRS) and mild to moderate subclinical atherosclerosis.ObjectiveTo assess whether statin therapy could slow progression and/or cause regression of carotid intima-media thickness (CIMT) over 2 years.Design, Setting, and ParticipantsRandomized, double-blind, placebo-controlled study (Measuring Effects on Intima-Media Thickness: an Evaluation of Rosuvastatin [METEOR]) of 984 individuals, with either age (mean, 57 years) as the only coronary heart disease risk factor or a 10-year FRS of less than 10%, modest CIMT thickening (1.2-<3.5 mm), and elevated LDL cholesterol (mean, 154 mg/dL); conducted at 61 primary care centers in the United States and Europe between August 2002 and May 2006.InterventionParticipants received either a 40-mg dose of rosuvastatin or placebo.Main Outcome MeasuresRate of change in maximum CIMT (assessed with B-mode ultrasound) for 12 carotid sites; changes in maximum CIMT of the common carotid artery, carotid bulb, and internal carotid artery sites and in mean CIMT of the common carotid artery sites. CIMT regression was assessed in the rosuvastatin group only.ResultsAmong participants in the rosuvastatin group, the mean (SD) baseline LDL cholesterol level of 155 (24.1) mg/dL declined to 78 (27.5) mg/dL, a mean reduction of 49% (P<.001 vs placebo group). The change in maximum CIMT for the 12 carotid sites was −0.0014 (95% CI, −0.0041 to 0.0014) mm/y for the rosuvastatin group vs 0.0131 (95% CI, 0.0087-0.0174) mm/y for the placebo group (P<.001). The change in maximum CIMT for the rosuvastatin group was −0.0038 (95% CI, −0.0064 to −0.0013) mm/y for the common carotid artery sites (P<.001), −0.0040 (95% CI, −0.0090 to 0.0010) mm/y for the carotid bulb sites (P<.001), and 0.0039 (95% CI, −0.0009 to 0.0088) mm/y for the internal carotid artery sites (P = .02). The change in mean CIMT for the rosuvastatin group for the common carotid artery sites was 0.0004 (95% CI, −0.0011 to 0.0019) mm/y (P<.001). All P values are vs placebo group. Overall, rosuvastatin was well tolerated with infrequent serious adverse cardiovascular events (6 participants [0.86%] had 8 events [1.1%] over 2 years).ConclusionsIn middle-aged adults with an FRS of less than 10% and evidence of subclinical atherosclerosis, rosuvastatin resulted in statistically significant reductions in the rate of progression of maximum CIMT over 2 years vs placebo. Rosuvastatin did not induce disease regression. Larger, longer-term trials are needed to determine the clinical implications of these findings.Trial Registrationclinicaltrials.gov Identifier: NCT00225589Published online March 25, 2007 (doi:10.1001/jama.297.12.1344).

Effect of Torcetrapib on Carotid Atherosclerosis in Familial Hypercholesterolemia

Abstract: After 24 months, in the atorvastatin-only group, the mean (±SD) HDL cholesterol level was 52.4±13.5 mg per deciliter and the mean low-density lipoprotein (LDL) cholesterol level was 143.2±42.2 mg per deciliter, as compared with 81.5±22.6 mg per deciliter and 115.1±48.5 mg per deciliter, respectively, in the torcetrapib–ato r va statin group. During the study, average systolic blood pressure increased by 2.8 mm Hg in the torcetrapib–atorvastatin group, as compared with the atorvastatinonly group. The increase in maximum carotid intima–media thickness, the primary measure of efficacy, was 0.0053±0.0028 mm per year in the atorvastatin-only group and 0.0047±0.0028 mm per year in the torcetrapib–atorvastatin group (P = 0.87). The secondary efficacy measure, annualized change in mean carotid intima–media thickness for the common carotid artery, indicated a decrease of 0.0014 mm per year in the atorvastatin-only group, as compared with an increase of 0.0038 mm per year in the torcetrapib–atorvastatin group (P = 0.005). Conclusions In patients with familial hypercholesterolemia, the use of torcetrapib with atorva statin, as compared with atorvastatin alone, did not result in further reduction of progression of atherosclerosis, as assessed by a combined measure of carotid arterial-wall thickness, and was associated with progression of disease in the common carotid segment. These effects occurred despite a large increase in HDL cholesterol levels and a substantial decrease in levels of LDL cholesterol and triglycerides. (ClinicalTrials.gov number, NCT00136981.)

Estimating interaction on an additive scale between continuous determinants in a logistic regression model

Abstract: Background To determine the presence of interaction in epidemiologic research, typically a product term is added to the regression model. In linear regression, the regression coefficient of the product term reflects interaction as departure from additivity. However, in logistic regression it refers to interaction as departure from multiplicativity. Rothman has argued that interaction estimated as departure from additivity better reflects biologic interaction. So far, literature on estimating interaction on an additive scale using logistic regression only focused on dichotomous determinants. The objective of the present study was to provide the methods to estimate interaction between continuous determinants and to illustrate these methods with a clinical example. Methods and results From the existing literature we derived the formulas to quantify interaction as departure from additivity between one continuous and one dichotomous determinant and between two continuous determinants using logistic regression. Bootstrapping was used to calculate the corresponding confidence intervals. To illustrate the theory with an empirical example, data from the Utrecht Health Project were used, with age and body mass index as risk factors for elevated diastolic blood pressure. Conclusions The methods and formulas presented in this article are intended to assist epidemiologists to calculate interaction on an additive scale between two variables on a certain outcome.

Cognitive and cardiac outcomes 5 years after off-pump vs on-pump coronary artery bypass graft surgery

Abstract: ContextConventional coronary artery bypass graft surgery with use of cardiopulmonary bypass (on-pump CABG) is associated with excellent long-term cardiac outcomes but also with a high incidence of cognitive decline. The effect of avoiding cardiopulmonary bypass (off-pump CABG) on long-term cognitive and cardiac outcomes is unknown.ObjectiveTo compare the effect of off-pump CABG and on-pump CABG surgery on long-term cognitive and cardiac outcomes.Design, Setting, and ParticipantsThe Octopus Study, a multicenter randomized controlled trial conducted in the Netherlands, which enrolled 281 low-risk CABG patients between 1998 and 2000. Five years after their surgery, surviving patients were invited for a follow-up assessment.InterventionPatients were randomly assigned to receive either off-pump (n = 142) or on-pump (n = 139) CABG surgery.Main Outcome MeasureThe primary measure was cognitive status 5 years after surgery, which was determined by a psychologist blinded to treatment allocation who administered 10 standardized validated neuropsychological tests. Secondary measures were occurrence of cardiovascular events (all-cause mortality, stroke, myocardial infarction, and coronary reintervention), anginal status, and quality of life.ResultsAfter 5 years, 130 patients were alive in each group. Cognitive outcomes could be determined in 123 and 117 patients in the off-pump and on-pump groups, respectively. When using a standard definition of cognitive decline (20% decline in performance in 20% of the neuropsychological test variables), 62 (50.4%) of 123 in the off-pump group and 59 (50.4%) of 117 in the on-pump group had cognitive decline (absolute difference, 0%; 95% confidence interval [CI], −12.7% to 12.6%; P>.99). When a more conservative definition of cognitive decline was used, 41 (33.3%) in the off-pump group and 41 (35.0%) in the on-pump group had cognitive decline (absolute difference, −1.7%; 95% CI, −13.7% to 10.3%; P = .79). Thirty off-pump patients (21.1%) and 25 on-pump patients (18.0%) experienced a cardiovascular event (absolute difference, 3.1%; 95% CI, −6.1% to 12.4%; P = .55). No differences were observed in anginal status or quality of life.ConclusionIn low-risk patients undergoing CABG surgery, avoiding the use of cardiopulmonary bypass had no effect on 5-year cognitive or cardiac outcomes.Trial Registrationisrctn.org Identifier: ISRCTN69438133

Self-Measurement of Blood Pressure at Home Reduces the Need for Antihypertensive Drugs A Randomized, Controlled Trial

Abstract: It is still uncertain whether one can safely base treatment decisions on self-measurement of blood pressure. In the present study, we investigated whether antihypertensive treatment based on self-measurement of blood pressure leads to the use of less medication without the loss of blood pressure control. We randomly assigned 430 hypertensive patients to receive treatment either on the basis of self-measured pressures (n=216) or office pressures (OPs; n=214). During 1-year follow-up, blood pressure was measured by office measurement (10 visits), ambulatory monitoring (start and end), and self-measurement (8 times, self-pressure group only). In addition, drug use, associated costs, and degree of target organ damage (echocardiography and microalbuminuria) were assessed. The self-pressure group used less medication than the OP group (1.47 versus 2.48 drug steps; P<0.001) with lower costs ($3222 versus $4420 per 100 patients per month; P<0.001) but without significant differences in systolic and diastolic OP values (1.6/1.0 mm Hg; P=0.25/0.20), in changes in left ventricular mass index (-6.5 g/m(2) versus -5.6 g/m(2); P=0.72), or in median urinary microalbumin concentration (-1.7 versus -1.5 mg per 24 hours; P=0.87). Nevertheless, 24-hour ambulatory blood pressure values at the end of the trial were higher in the self-pressure than in the OP group: 125.9 versus 123.8 mm Hg (P<0.05) for systolic and 77.2 versus 76.1 mm Hg (P<0.05) for diastolic blood pressure. These data show that self-measurement leads to less medication use than office blood pressure measurement without leading to significant differences in OP values or target organ damage. Ambulatory values, however, remain slightly elevated for the self-pressure group.

Carotid intima-media thickness and coronary atherosclerosis: weak or strong relations?

Abstract: Aims Measurement of change in carotid intima-media thickness (CIMT) has been proposed as an alternative for the occurrence of cardiovascular (CV) events in the assessment of therapeutic interventions. Nevertheless, criticism has been voiced based on observations indicating a weak relation between CIMT and coronary atherosclerosis as well as on the virtual absence of data showing that progression of CIMT indeed predicts coronary artery disease (CAD) and stroke. Methods and results We set out to review the evidence on these issues by performing a literature search on these topics. Of the 34 studies on the relation of CIMT with coronary atherosclerosis, as assessed by angiography ( n = 33) or intravascular ultrasound ( n = 1), 30 showed a modest positive relationship; the magnitude of which was similar to that found in autopsy studies. Of all studies on CIMT and future CV events ( n = 18), 17 showed graded positive relationships. At present, only one study has provided evidence on the relation of change in CIMT and future CV events, showing an increased risk with CIMT progression. The paucity of data on progression and future CV risk is partly attributable to time windows required to complete these studies. Conclusion The modest relation between CIMT and coronary atherosclerosis most likely reflects variability in atherosclerosis development between the vascular beds rather than limitations of CIMT measurements. Additional data on the relation between change in CIMT and future CV events is required and currently is in progress.

Sodium and potassium intake and risk of cardiovascular events and all-cause mortality : the Rotterdam Study

Abstract: Background Dietary electrolytes influence blood pressure, but their effect on clinical outcomes remains to be established. We examined sodium and potassium intake in relation to cardiovascular disease (CVD) and mortality in an unselected older population. Methods A case–cohort analysis was performed in the Rotterdam Study among subjects aged 55 years and over, who were followed for 5 years. Baseline urinary samples were analyzed for sodium and potassium in 795 subjects who died, 206 with an incident myocardial infarction and 181 subjects with an incident stroke, and in 1,448 randomly selected subjects. For potassium, dietary data were additionally obtained by food-frequency questionnaire for 78% of the cohort. Results There was no consistent association of urinary sodium, potassium, or sodium/potassium ratio with CVD and all-cause mortality over the range of intakes observed in this population. Dietary potassium estimated by food frequency questionnaire, however, was associated with a lower risk of all-cause mortality in subjects initially free of CVD and hypertension (RR = 0.71 per standard deviation increase; 95% confidence interval: 0.51–1.00). We observed a significant positive association between urinary sodium/potassium ratio and all-cause mortality, but only in overweight subjects who were initially free of CVD and hypertension (RR = 1.19 (1.02–1.39) per unit). Conclusion The effect of sodium and potassium intake on CVD morbidity and mortality in Western societies remains to be established.

Predictors of mortality after aortic valve replacement

Abstract: Aortic valve replacement (AVR) is recommended as a standard surgical procedure for aortic valve disease. Still the evidence for commonly claimed predictors of post-AVR prognosis, in particular mortality, appears scant. This systematic review reports on the evidence for predictors of post-AVR mortality, and may be helpful in pre-surgical risk-stratification. In PubMed, we searched for original reports of post-AVR follow-up studies. We assessed the quality of study design and methods with a standardized checklist. Data of the reported predictors of mortality and outcomes were extracted. Twenty-eight studies met our inclusion criteria. Sixteen studies were considered of high quality. There is strong evidence that the risk of early mortality is increased by emergency surgery, while the risk of late mortality is increased with older age and preoperative atrial fibrillation. There is moderate evidence that the risk of early mortality is increased by older age, aortic insufficiency, coronary artery disease, longer cardiopulmonary bypass time, reduced left ventricular ejection fraction (LV-EF), infective endocarditis, hypertension, mechanical valves, preoperative pacing, dialysis-dependent renal failure and valve size; and that the risk for late mortality is increased by emergency surgery and urgency of the operation. There is little evidence for high New York Heart Association class, concomitant coronary artery bypass graft and many other commonly claimed risk factors for post-AVR mortality. The reported evidence on predictors of post-AVR mortality will help for pre-surgical risk-stratification, i.e. to discern patients at high or low risk for early and late post-AVR mortality. Future prognostic studies should take the evidence from this review into account and should focus on derivation of a predictive model for post-AVR survival.

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

Abstract: 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.

Depressive symptoms in subjects with diagnosed and undiagnosed type 2 diabetes.

Abstract: Objective: To investigate if disturbed glucose homeostasis or known diagnosis of diabetes was associated with depressive symptoms. The reason for the increased prevalence of depression in patients with Type 2 diabetes mellitus (DM2) is unknown. Methods: Within the Utrecht Health Project, an ongoing longitudinal study among inhabitants of a residential area of a large city in The Netherlands, 4747 subjects (age: 39.4 +/- 12.5 years) were classified into four mutually exclusive categories: normal fasting plasma glucose (FPG) (= 5.6 and = 7.0 mmol/l), and diagnosed DM2. Presence of depressive symptoms was defined as a score of >= 25 on the depression subscale of the Symptom Check List (SCL-90) or self-reported use of antidepressants. Results: Diagnosed DM2 was associated with an increased risk of depressive symptoms (odds ratio (OR) = 1.69; 95% confidence interval (CI) 1.06-2.72) after adjustment for demographic and lifestyle variables. Additional adjustment for number of chronic diseases reduced the OR to 1.36 (95% CI 0.83-2.23). Impaired fasting glucose and undiagnosed DM2 were not associated with depressive symptoms. Conclusions: Our findings suggest that disturbed glucose homeostasis is not associated with depressive symptoms. The increased prevalence of depressive symptoms among patients with diagnosed DM2 suggests that depressive symptoms might be a consequence of the burden of diabetes. The number of chronic diseases seems to explain part of the association between DM2 and depressive symptoms.

In-hospital morbidity and mortality due to severe malarial anemia in western Kenya.

Abstract: Severe malarial anemia (SMA) is a leading cause of pediatric morbidity, hospitalization, and mortality in sub-Saharan Africa, and yet its contribution to malaria-specific mortality is not well documented. We retrospectively reviewed the clinical records of 1,116 children < 5 years of age admitted to Siaya district hospital, western Kenya, to assess the contribution of SMA to overall in-hospital mortality. Of 1,116 admissions, 86% were under 3 years, 83% had malaria parasitemia, 86% were anemic, 21% were severely anemic, and 20% were transfused. Severe anemia was associated with parasitemia in 85% of the admissions and contributed to 53% of malaria-related deaths. Overall, 83 (7.5%) children died; 66% of those deaths were malaria-related, 12% had severe anemia, and 89% were under 3 years. Transfusion did not lower mortality rates. In areas of high malaria transmission, children below 3 years are a high-risk group for malaria, anemia, blood transfusion, and mortality.

EPIC-Heart: The cardiovascular component of a prospective study of nutritional, lifestyle and biological factors in 520,000 middle-aged participants from 10 European countries

Abstract: EPIC-Heart is the cardiovascular component of the European Prospective Investigation into Cancer and Nutrition (EPIC), a multi-centre prospective cohort study investigating the relationship between nutrition and major chronic disease outcomes. Its objective is to advance understanding about the separate and combined influences of lifestyle (especially dietary), environmental, metabolic and genetic factors in the development of cardiovascular diseases by making best possible use of the unusually informative database and biological samples in EPIC. Between 1992 and 2000, 519,978 participants (366,521 women and 153,457 men, mostly aged 35-70 years) in 23 centres in 10 European countries commenced follow-up for cause- specific mortality, cancer incidence and major cardiovascular morbidity. Dietary information was collected with quantitative questionnaires or semi-quantitative food frequency questionnaires, including a 24-h dietary recall sub-study to help calibrate the dietary measurements. Information was collected on physical activity, tobacco smoking, alcohol consumption, occupational history, socio-economic status, and history of previous illnesses. Anthropometric measurements and blood pressure recordings were made in the majority of participants. Blood samples were taken from 385,747 individuals, from which plasma, serum, red cells, and buffy coat fractions were separated and aliquoted for long-term storage. By 2004, an estimated 10,000 incident fatal and non-fatal coronary and stroke events had been recorded. The first cycle of EPIC-Heart analyses will assess associations of coronary mortality with several prominent dietary hypotheses and with established cardiovascular risk factors. Subsequent analyses will extend this approach to non-fatal cardiovascular outcomes and to further dietary, biochemical and genetic factors.

Comparison of B-type natriuretic peptide assays for identifying heart failure in stable elderly patients with a clinical diagnosis of chronic obstructive pulmonary disease.

Abstract: Aims: To compare the ability of different B-type natriuretic peptide (BNP) assays to identify heart failure in stable elderly patients with a diagnosis of chronic obstructive pulmonary disease (COPD). Methods: 200 patients aged ≥65 years with COPD according to their general practitioner and without known heart failure, underwent a diagnostic work-up. The final diagnosis of heart failure was established by a panel using the diagnostic principles of the European Society of Cardiology. All available diagnostic results, including echocardiography, but not BNP or NT-proBNP measurements, were used. The ability of different B-type natriuretic peptide assays to identify heart failure was estimated using the area under the receiver operating characteristic curves (ROC-area). Results: The ROC-areas did not differ significantly between the various assays of NT-proBNP and BNP, and ranged from 0.68 (95%CI 0.60–0.73) to 0.73 (95%CI 0.64–0.81). For NT-proBNP the age- and gender-independent “optimal” cut-point was 15 pmol/l (125 pg/ml) and for BNP 10 pmol/l (35 pg/ml). All assays were much better at excluding than detecting heart failure. Conclusions: All assays of B-type natriuretic peptide showed reasonable and comparable accuracy in recognising heart failure. At “optimal” cut-points, all assays performed better at excluding than detecting new cases of heart failure in this population.

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

Abstract: 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.

Validating and updating a prediction rule for serious bacterial infection in patients with fever without source.

Abstract: Aim: To externally validate and update a previously developed rule for predicting the presence of serious bacterial infections in children with fever without apparent source. Methods: Patients, 1–36 mo, presenting with fever without source, were prospectively enrolled. Serious bacterial infection included bacterial meningitis, sepsis, bacteraemia, pneumonia, urinary tract infection, bacterial gastroenteritis, osteomyelitis/ethmoiditis. The generalizability of the original rule was determined. Subsequently, the prediction rule was updated using all available data of the patients with fever without source (1996–1998 and 2000–2001, n = 381) using multivariable logistic regression. Results: the generalizability of the rule appeared insufficient in the new patients (n = 150). In the updated rule, independent predictors from history and examination were duration of fever, vomiting, ill clinical appearance, chest-wall retractions and poor peripheral circulation (ROC area (95%CI): 0.69 (0.63–0.75)). Additional independent predictors from laboratory were serum white blood cell count and C-reactive protein, and in urinalysis ≥70 white bloods (ROC area (95%CI): 0.83 (0.78–0.88). Conclusions: A previously developed prediction rule for predicting the presence of serious bacterial infection in children with fever without apparent source was updated. Its clinical score can be used as a first screening tool. Additional laboratory testing may specify the individual risk estimate (range: 4–54%) further.

Predicting serious bacterial infection in young children with fever without apparent source.

Abstract: The aim of this study was to design a clinical rule to predict the presence of a serious bacterial infection in children with fever without apparent source. Information was collected from the records of children aged 1‐36 mo who attended the paediatric emergency department because of fever without source (temperature ¶38°C and no apparent source found after evaluation by a general practitioner or history by a paediatrician). Serious bacterial infection included bacterial meningitis, sepsis, bacteraemia, pneumonia, urinary tract infection, bacterial gastroenteritis, osteomyelitis and ethmoiditis. Using multivariate logistic regression and the area under the receiver operating characteristic curve (ROC area), the diagnostic value of predictors for serious bacterial infection was judged, resulting in a risk stratie cation. Twenty-e ve percent of the 231 patients enrolled in the study (mean age 1.1 y) had a serious bacterial infection. Independent predictors from history and examination included duration of fever, poor micturition, vomiting, age, temperature <36.7°C or ¶40°C at examination, chest-wall retractions and poor peripheral circulation (ROC area: 0.75). Independent predictors from laboratory tests were white blood cell count, serum C-reactive protein and the presence of ¶70 white blood cells in urinalysis (ROC area: 0.83). The risk stratie cation for serious bacterial infection ranged from 6% to 92%.

Tobacco Smoke Exposure of Pregnant Mothers and Blood Pressure in Their Newborns: Results from the Wheezing Illnesses Study Leidsche Rijn Birth Cohort

Abstract: There is evidence to suggest that exposure of pregnant women to tobacco smoke is related to higher childhood blood pressure in their offspring. It is not well known whether this association is set in utero or by shared postnatal environments. The objective of this study was to assess the association between tobacco smoke exposure of pregnant mothers and blood pressure and heart rate of their newborns. In an unselected birth cohort, blood pressure and heart rate were measured in 456 infants at ≈2 months of age. Smoking exposure of mothers in pregnancy was obtained by questionnaire. Of 456 mothers whose infants had blood pressure measured, 363 (79.6%) were not exposed to tobacco smoke in pregnancy, 63 (13.8%) did not smoke in pregnancy but were exposed by others, and 30 (6.6%) smoked. Infant offspring of mothers who had smoked during pregnancy had 5.4 mm Hg (95% CI: 1.2 to 9.7; P =0.01) higher systolic blood pressure levels than offspring of mothers who were not exposed to tobacco smoke in pregnancy, taking account of birth weight, infant age, gender, nutrition, and age of mother. No associations were found between maternal exposure to tobacco smoke in pregnancy and diastolic blood pressure. A positive association between maternal exposure to tobacco smoke and heart rate was largely explained by confounding. It can be concluded that maternal exposure to tobacco smoke in pregnancy has a substantial increasing effect on systolic blood pressure in early infancy.

Physical Inactivity, Depression, and Risk of Cardiovascular Mortality

Abstract: Purpose: Studies indicate that depression may increase risk of cardiovascular disease (CVD) in addition to classical risk factors. One of the hypotheses to explain this relation is that depressed subjects become physically inactive. We set out to determine the role of physical inactivity in the relation between depressive symptoms and cardiovascular mortality. Methods: Data were used from the population-based prospective Finland, Italy, and the Netherlands Elderly (FINE) Study. Depressive symptoms were measured with the Zung Self-Rating Depression Scale in 909 elderly men, aged 70-90 yr, free of CVD and diabetes at baseline in 1990. Physical activity was assessed with a questionnaire for retired men. Hazard ratios (HR) for 10-yr cardiovascular mortality were calculated, adjusting for demographics and cardiovascular risk factors. Results: At baseline, men with more depressive symptoms were less physically active (722 min.wk(-1); 95% confidence interval (CI), 642-802) than men with few depressive symptoms (919 min.wk(-1); 95% CI, 823-1015). During 10 yr of follow-up, 256 (28%) men died from CVD. The adjusted HR of cardiovascular mortality for a decrease of 30 min.d(-1) in physical activity was 1.09 (95% CI, 1.04-1.14). An increase in depressive symptoms with one standard deviation was associated with a higher cardiovascular mortality risk (HR = 1.42; 95% CI, 1.26-1.60). After additional adjustment for physical activity the risk decreased (9%), but an independent risk remained (HR = 1.37; 95% CI, 1.21-1.56). The excess risk on cardiovascular mortality attributable to the combined effect of depressive symptoms with inactivity was 1.47 (95% CI, -0.17 to 3.11). Conclusions: In the present study, the increased risk of depressive symptoms on cardiovascular mortality could not be explained by physical inactivity. However, our results suggest that depressive symptoms and physical inactivity may interact to increase cardiovascular mortality risk.

No increased incidence of diabetes in antidepressant users.

Abstract: This study investigated whether the association between depression and diabetes was influenced by the presence of chronic somatic disease. To distinguish between depression and other psychosocial complaints, we studied the onset of diabetes in antidepressant (AD) users and benzodiazepine (BD) users, respectively. From the PHARMO database, which includes complete drug prescription data, we identified subjects using (i) no ADs and no BDs; (ii) AD but no BD; (iii) BD but no AD; and (iv) AD and BD. A total of 60 516 individuals (age: 45.5+/-17 years; 42.1% men) were followed from their first prescription for AD or BD until end of registration or a first prescription for antidiabetic drugs. The crude incidence rate in AD but no BD users was not increased compared with no AD and no BD users. After adjustment for age, sex and chronic diseases, the hazard ratios (95% confidence interval) were 1.05 (0.88-1.26) for AD but no BD users, 1.21 (1.02-1.43) for BD but no AD users and 1.37 (1.12-1.68) for AD and BD users compared with no AD and no BD users. We did not find an increased risk of diabetes in individuals using ADs. The association between BD use and diabetes was partly explained by chronic somatic comorbidity.

Short- and long-term mortality after acute myocardial infarction: comparison of patients with and without diabetes mellitus

Abstract: Aims To compare short- and long-term mortality after a first acute myocardial infarction (AMI) in patients with and without diabetes mellitus. Methods and results A nationwide cohort of 2,018 diabetic and 19,547 nondiabetic patients with a first hospitalized AMI in 1995 was identified through linkage of the national hospital discharge register and the population register. Follow-up for mortality lasted until the end of 2000. At 28 days and 5 years respectively, absolute mortality risks were 18 and 53% in diabetic men, 12 and 31% in nondiabetic men, 22 and 58% in diabetic women, and 19 and 42% in nondiabetic women. Crude mortality was significantly higher in diabetic patients than in nondiabetic patients in both men (28-day hazard ratio (HR) 1.55; 95% confidence interval (CI) 1.32–1.81, 5-year HR 2.01; 95% CI 1.84–2.21) and women (28-day HR 1.19; 95% CI 1.03–1.37, 5-year HR 1.53; 95% CI 1.40–1.67). After multivariate adjustment, risk differences became nonsignificant at 28 days, but diabetes was still associated with a significantly higher long-term mortality in both men (28-day HR 1.16; 95% CI 0.99–1.36, 5-year HR 1.49; 95% CI 1.36–1.64) and women (28-day HR 1.12; 95% CI 0.97–1.28, 5-year HR 1.39; 95% CI 1.27–1.52). The interaction between diabetes mellitus and gender did not reach significance in the analyses. Conclusion Our findings in an unselected cohort covering a complete nation show a significantly higher long-term mortality after a first acute myocardial infarction in diabetic patients. Yet, short-term mortality is not significantly higher in diabetic patients. Risks appear to be equally elevated in men and women.

Dietary Phytoestrogen Intake and Cognitive Function in Older Women

Abstract: Background. Aging is associated with a decline in cognitive function; we explored the possible influence of dietary phytoestrogens on this decline. Methods. We conducted a cross-sectional study in 301 Dutch women aged 60-75 years. Dietary isoflavone and lignan intake was assessed with a food-frequency questionnaire covering habitual diet in the year preceding enrolment. The endpoints were cognitive function measured in three domains: memory, processing capacity and speed, and executive function. Data were analyzed using linear regression models, after adjusting for confounders. Results. No association between dietary isoflavone intake and cognitive function was found. High lignan intake was associated with a better performance in processing capacity and speed, and in executive function (p for trend over quartiles =.01 and.02, respectively). Conclusions. This finding calls for further research to elucidate the relatively underexplored role of lignans within the range of phytoestrogens.

Autonomic dysfunction: a link between depression and cardiovascular mortality? The FINE Study.

Abstract: Background: Depression is associated with an increased risk of cardiovascular diseases (CVD) in vascular patients as well as in the general population. We investigated whether autonomic dysfunction could explain this relationship. Design: The Finland, Italy and The Netherlands Elderly (FINE) Study is a prospective cohort study. Methods: Depressive symptoms were measured with the Zung Self-rating Depression Scale in 870 men, aged 70-90 years, free of CVD and diabetes in 1990. Resting heart rate was determined from a 15-30-s resting electrocardiogram in The Netherlands and Italy and as pulse rate in Finland. In addition, in The Netherlands, heart-rate variability (HRV) and QTc interval were determined. Results: At baseline, depressive symptoms were associated with an increase in resting heart rate, and nonsignificantly with low HRV and prolonged QTc interval. After 10 years of follow-up, 233 (27%) men died from CVD. Prospectively, an increase in resting heart rate with 1 SD was associated with an increased risk of cardiovascular mortality [hazard ratio (HR), 1.22; 95% confidence interval (CI), 1.08-1.38]. In addition, low HRV (HR, 0.78; 95% CI, 0.61-1.01) and prolonged QTc interval (HR, 1.28; 95% CI, 1.06-1.53) per SD were associated with cardiovascular mortality. The increased risk of depressive symptoms for cardiovascular mortality (HR, 1.38; 95% CI, 1.21-1.58) did not change after adjustments for several indicators of autonomic dysfunction. Conclusion: This study suggests that mild depressive symptoms are associated with autonomic dysfunction in elderly men. The increased risk of cardiovascular mortality with increasing magnitude of depressive symptoms could, however, not be explained by autonomic dysfunction.

High Blood Pressure in Pregnancy and Coronary Calcification

Abstract: A considerable proportion of pregnant women develop high blood pressure in pregnancy. Although it is assumed that this condition subsides after pregnancy, many of these women develop the metabolic syndrome later in life and are at increased risk to develop coronary heart disease. Atherosclerosis development is considered in between risk factors and occurrence of vascular symptoms. We set out to cross-sectionally study the relation of high blood pressure during pregnancy with risk of coronary calcification. The study population was composed 491 healthy postmenopausal women selected from a population-based cohort study. Information on high blood pressure during pregnancy was obtained using a questionnaire. Between 2004 and 2005, the women underwent a multidetector computed tomography (Philips Mx 8000 IDT 16) to assess coronary calcium. The Agatston score, volume, and mass measurements were used to quantify coronary calcium. A total of 30.7% of the women reported to have had high blood pressure in pregnancy. Body mass index (odds ratio [OR]: 1.05; 95% CI: 1.01 to 1.09) and diastolic blood pressure (OR: 1.03; 95% CI: 1.01 to 1.05) were significantly related to a history of high blood pressure in pregnancy. Age was significantly related to increased coronary calcification. Women with a history of high blood pressure during pregnancy had a 57% increased risk of having coronary calcification compared with those women without this condition (OR: 1.57; 95% CI: 1.04 to 2.37). After adjusting for age, the relation did not change (OR: 1.64; 95% CI: 1.07 to 2.53). We concluded that high blood pressure during pregnancy is associated with an increased risk of coronary calcification later in life.

No relationship between circulating levels of sex steroids and mammographic breast density: the Prospect-EPIC cohort

Abstract: Background High breast density is associated with increased breast cancer risk. Epidemiologic studies have shown an increase in breast cancer risk in postmenopausal women with high levels of sex steroids. Hence, sex steroids may increase postmenopausal breast cancer risk via an increase of breast density. The objective of the present study was to study the relation between circulating oestrogens and androgens as well as sex hormone binding globulin (SHBG) in relation to breast density.