Evidence for genetic factors explaining the birthweight-blood pressure relation: analysis in twins.

Abstract—Epidemiological studies have consistently shown an inverse association between birth weight and systolic blood pressure in later life after adjustment for current size. To examine whether this association is explained by intrauterine or genetic factors, we investigated birth weight and blood pressure data in 53 dizygotic and 61 monozygotic adolescent twin pairs. Birth weight was obtained from the mothers. Blood pressure measurements were performed 6 times at rest and during mental stress. The dizygotic but not the monozygotic twins with the lowest birth weight from each pair had a systolic blood pressure measured at rest and during the reaction time experiment that was higher compared with their cotwins with the highest birth weight (dizygotic twins: blood pressure at rest, 119.4�9.7 mm Hg versus 117.3�8.5 mm Hg, P�0.07, and during a reaction time task, 126.2�10.8 versus 123.6�9.5, P�0.09; monozygotic twins: blood pressure at rest, 117.4�6.4 versus 118.4�9.0, P�0.4, and during a reaction time task, 122.9�8.4 versus 124.2�10.8, P�0.2). The differences in blood pressure between the cotwins with the lowest and the cotwins with the highest birth weight were different in dizygotic compared with monozygotic twin pairs (for blood pressure at rest, P�0.05; for blood pressure during reaction time, P�0.03). After adjustment for differences in current weight, intrapair differences in birth weight were negatively and significantly associated with differences in systolic blood pressure at rest and during the reaction time task in dizygotic twins (regression coefficient, �5.7 mm Hg/kg [95 % confidence interval, �10.4 to �1.0] and �6.3 [�12.7 to 0], respectively) but not in monozygotic twins (�0.1 [�5.4 to 5.2] and �3.5 [�1.

Microalbuminuria is strongly associated with NIDDM and hypertension, but not with the insulin resistance syndrome: the Hoorn study

Microalbuminuria is a strong predictor of cardiovascular disease. The aim of this study was to investigate whether microalbuminuria is part of a cluster of risk factors, the insulin resistance syndrome (IRS), or whether it is only associated with, and presumably a complication of, hypertension and non-insulin-dependent diabetes mellitus (NIDDM). An age-, sex- and glucose tolerance-stratified random sample from a 50-75 year old general population (n = 622) was investigated. The urinary albumin-to-creatinine ratio was measured in an early morning spot urine sample. Microalbuminuria was defined as an albumin-to-creatinine ratio greater than 2.0 mg/mmol. We considered, as IRS-related variables, fasting hyperinsulinaemia, insulin resistance (IR; calculated from the formula of the homeostasis model assessment), dyslipidaemia, glucose intolerance, hypertension and waist-to-hip ratio (WHR). Dyslipidaemia was defined as levels of HDL-cholesterol in the lowest and/or levels of triglyceride in the highest tertile. Fasting insulin levels, IR and WHR were divided into tertiles; the highest tertiles were compared to the lowest tertiles. Age-, sex- and glucose tolerance-adjusted analyses showed microalbuminuria to be significantly associated with hypertension, NIDDM and WHR. In multiple logistic regression analyses, microalbuminuria showed independent associations with hypertension, NIDDM and WHR, with odds ratios (ORs [95% confidence interval]) of 3.33 (1.86-5.96), 2.26 (1.14-4.48) and 2.49 (1.09-5.70), respectively. No associations were found with impaired glucose tolerance, hyperinsulinaemia, IR or dyslipidaemia. Multiple logistic regression analyses in diabetic and non-diabetic subjects separately showed that microalbuminuria was independently associated only with hypertension (ORs 4.31 and 2.69). In this Caucasian population, microalbuminuria was associated with hypertension, NIDDM and WHR and not with other variables of the IRS. It is therefore likely that microalbuminuria is a complication of hypertension and NIDDM, and not an integral part of the IRS

High risk of cardiovascular mortality in individuals with impaired fasting glucose is explained by conversion to diabetes - The Hoorn Study

OBJECTIVE: To optimize identification of future diabetic patients, the American Diabetes Association (ADA) introduced criteria for impaired fasting glucose (IFG) in 1997 (IFG 6.1 mmol/l [IFG6.1]) and lowered the threshold from 6.1 to 5.6 mmol/l (IFG5.6) in 2003. Our aim was to assess the consequences of lowering the IFG cutoff on the risk of cardiovascular disease (CVD) mortality and to evaluate whether this risk is explained by a conversion to type 2 diabetes within 6.4 years. RESEARCH DESIGN AND METHODS: In a population-based cohort, the Hoorn Study, plasma glucose was determined in 1989 and 1996 (n = 1,428). Subjects were classified in 1989 according to 1997 and 2003 ADA criteria. Subjects with IFG in 1989 were further classified according to diabetes status in 1996. Hazard ratios for CVD mortality (n = 81) in the period 1996-2005 were adjusted for age and sex. RESULTS: Subjects with IFG6.1, but not IFG5.6, had a significantly higher CVD mortality risk than normal fasting glucose (NFG) subjects. Subjects who converted from IFG to diabetes (IFG6.1: 42%; IFG5.6: 21%) had a more than twofold risk of CVD mortality (IFG6.1: 2.47 [1.17-5.19]; IFG5.6: 2.14 [1.12-4.10]) than subjects with NFG. IFG subjects who did not develop diabetes did not have significantly higher CVD mortality risks (IFG6.1: 1.50 [0.72-3.15]; IFG5.6: 1.15 [0.69-1.93]). CONCLUSIONS: The lower cutoff for IFG (ADA 2003 criteria) results in a category of IFG that no longer represents a high-risk state of CVD. Furthermore, only subjects who convert from IFG to diabetes have a high risk of CVD mortality

Metabolic syndrome and 10-year cardiovascular disease risk in the Hoorn study

BACKGROUND: Different definitions of the metabolic syndrome have been proposed. Their value in a clinical setting to assess cardiovascular disease (CVD) risk is still unclear. We compared the definitions proposed by the National Cholesterol Education Program Adult Treatment Panel III (NCEP), World Health Organization (WHO), European Group for the Study of Insulin Resistance (EGIR), and American College of Endocrinology (ACE) with respect to the prevalence of the metabolic syndrome and the association with 10-year risk of fatal and nonfatal CVD. METHODS AND RESULTS: The Hoorn Study is a population-based cohort study. The present study population comprised 615 men and 749 women aged 50 to 75 years and without diabetes or a history of CVD at baseline in 1989 to 1990. The prevalence of the metabolic syndrome at baseline ranged from 17% to 32%. The NCEP definition was associated with about a 2-fold increase in age-adjusted risk of fatal CVD in men and nonfatal CVD in women. For the WHO, EGIR, and ACE definitions, these hazard ratios were slightly lower. Risk increased with the number of risk factors. Elevated insulin levels were more prevalent in subjects with multiple risk factors, but metabolic syndrome definitions including elevated insulin level were not more strongly associated with risk. CONCLUSIONS: The metabolic syndrome, however defined, is associated with an approximate 2-fold increased risk of incident cardiovascular morbidity and mortality in a European population. In clinical practice, a more informative assessment can be obtained by taking into account the number of individual risk factor

Improvement of glycaemic control in type 2 diabetes: favourable changes in blood pressure, total cholesterol and triglycerides, but not in HDL cholesterol, fibrinogen, von Willebrand factor and (pro)insulin

Background: Diabetes mellitus causes a substantial increase in cardiovascular risk, which can only partly be reduced by antihyperglycaemic treatment. We were interested in whether improvement in glycaemic control is associated with improvement of other cardiovascular risk factors. Therefore, we studied among type 2 diabetic patients the association between on the one hand changes in glycaemic control and on the other hand within-subject changes of both classic cardiovascular risk factors and less conventional cardiovascular risk indicators that are typically associated with type 2 diabetes (proinsulin, insulin, fibrinogen, von Willebrand factor and the urinary albumin-creatinine ratio). Methods: The 214 type 2 diabetic patients were randomly assigned to either a strict fasting capillary glucose target level (<6.5 mmol/l) or a less strict target (<8.5 mmol/l). Duration of follow-up was two years. Since the interventions did not yield statistically significant differences between the treatment arms, we reanalysed the data focusing on within-subject changes of cardiovascular risk factors and indicators across tertiles of average HbAIC. Results: Individuals in whom HbAIC decreased had significant favourable concurrent changes in triglycerides, total cholesterol, blood pressure, and in the albumin-creatinine ratio in those who were normoalbuminuric at baseline. In contrast, these individuals had unfavourable, although not statistically significant, changes in HDL cholesterol, proinsulin, insulin, fibrinogen and von Willebrand factor. In the whole group, fibrinogen increased more than could be expected on the basis of the relationship between fibrinogen and age, namely from 3.5 ± 0.8 to 3.9 ± 0.9 g/l (p value <0.01). Conclusions: Our results suggest that improvement in glycaemia in type 2 diabetes is associated with significant favourable changes in triglycerides, total cholesterol, blood pressure and, in normoalbuminuric individuals, albumin-creatinine ratio. In contrast, it is not consistently associated with favourable changes in some cardiovascular risk indicators typically associated with diabetes, which may in part explain why antihyperglycaemic treatment does not clearly lower atherothrombotic disease risk

Endothelial dysfunction contributes to renal function-associated cardiovascular mortality in a population with mild renal insufficiency: The Hoorn study

Mildly impaired renal function is associated with cardiovascular morbidity and mortality. There are indications that endothelial dysfunction and/or chronic inflammation, which play an important role in atherothrombosis, are present in early stages of renal insufficiency. This study investigated whether and to which extent endothelial dysfunction and inflammation were related to renal function and contributed to renal function-associated cardiovascular mortality in a population-based cohort (n = 613), aged 50 to 75 yr, that was followed with a median duration of 12.5 yr. During follow-up, 192 individuals died (67 of cardiovascular causes). At baseline, renal function was estimated with serum creatinine, the Cockcroft-Gault formula, and the Modification of Diet in Renal Disease equation of GFR (eGFR). Endothelial function was estimated by plasma von Willebrand factor, soluble vascular cell adhesion molecule-1, and the urinary albumin-creatinine ratio. Inflammatory activity was estimated by plasma C-reactive protein and soluble intercellular adhesion molecule-1. Renal function was mildly impaired (mean eGFR 68 ± 12 ml/min per 1.73