An exploratory analysis of criteria for the metabolic syndrome and its prediction of long-term cardiovascular outcomes: the Hoorn study

Studies have shown an increased risk of cardiovascular outcomes with the metabolic syndrome, but information on predictive properties of the National Cholesterol Education Program Adult Treatment Panel 3 (NCEP) criteria is sparse. The authors used data from the Hoorn population-based study in the Netherlands including 2,484 participants aged 50-75 years examined in 1989 and followed for cardiovascular morbidity and mortality through 2000 to assess NCEP criteria, excluding known diabetes or cardiovascular disease. Cluster analyses explored whether NCEP identifies a mixture of heterogeneous groups. For each gender, participants meeting NCEP criteria seemed to be divided into clusters distinguished primarily by triglycerides or high density lipoprotein cholesterol. Cutpoints for components predicting cardiovascular events using classification and survival tree methodology varied by endpoint and gender, but Cox model hazards ratios were relatively comparable regardless of cutpoints (range: 1.3-2.5). Clear gradation in risk of cardiovascular outcomes was evident with increasing number of components, with statistically elevated risk for >or=3 (NCEP) components in men but for >or=2 components in women. Exploratory analyses of alternative metabolic syndrome criteria suggest cardiovascular risk estimates comparable to those derived by using NCEP, but criteria evaluating risk on more of a continuum would potentially allow consideration of alternative definitions by gender or for patients with other risk factors.     

Mild renal insufficiency is associated with increased left ventricular mass in men, but not in women: an arterial stiffness-related phenomenon--the Hoorn Study

BACKGROUND: Mild renal insufficiency has recently been recognized as an important risk factor for cardiovascular disease (CVD). The mechanisms underlying this association are incompletely understood. Increased left ventricular mass (LVM) is an independent risk factor for CVD, which is particularly common in end-stage renal disease (ESRD) and which has been shown to be associated with mild renal insufficiency. Increased arterial stiffness has also been shown to be an independent risk factor for CVD in ESRD and has also been associated with mild renal insufficiency. We hypothesized that the association between mild renal insufficiency and increased LVM could be mediated through increased arterial stiffness, and that this may be one of the pathways linking mild renal insufficiency to CVD. We therefore investigated, in a cross-sectional population-based study, the influence of increased arterial stiffness on the association between renal function and LVM. METHODS: The study population consisted of 742 elderly individuals (373 men and 369 women). Renal function was estimated by the serum creatinine level in micromol/L; by the Cockcroft-Gault formula in mL/min and by the Modification of Diet in Renal Disease (MDRD) formula. LVM was obtained by echocardiography. RESULTS: The mean estimates of renal function in men and women were, respectively, 103.7 (SD 17.0) and 86.8 (SD 11.2) micromol/L for the serum creatinine level; 63.4 (SD 12.9) and 61.4 (SD 11.0) mL/min/1.73 m(2) for the Cockcroft-Gault formula; and 59.7 (SD 10.8) and 60.9 (SD 10.5) mL/min per 1.73 m(2) for the MDRD formula. LVM was 93.1 (SD 26.4) g/m(2) in men and 86.7 (SD 22.3) g/m(2) in women. In men, impaired renal function, as estimated by the Cockcroft-Gault and the MDRD formula, was significantly associated with greater LVM after adjustment for age, glucose tolerance, hypertension, and prior CVD [regression coefficient beta (95% CI), 1.28 (0.22 to 2.33) g/m(2) and 1.63 (0.41 to 2.86) g/m(2) per 5 mL/min/1.73 m(2) decrease, respectively]. However, the association between impaired renal function and increased LVM was not statistically significant after adjustment for arterial stiffness estimates [regression coefficient beta (95% CI), 0.02 (-1.60 to 1.64) g/m(2) and 0.54 (-1.25 to 2.33) g/m(2) per 5 mL/min/1.73 m(2) decrease, respectively]. In women, impaired renal function was not significantly associated with greater LVM. CONCLUSION: Our study shows that in a general elderly population, even mild impairment of renal function is associated with adverse changes in left ventricular structure. In men, but not in women, this leads to greater LVM, a process that may be related to increases in arterial stiffness. Importantly, these novel findings suggest that such changes occur early in the process of renal functional deterioration, which may explain, in part, the increase in cardiovascular risk in men with mildly impaired renal function.     

Opposite contributions of trunk and leg fat mass with plasma lipase activities: the Hoorn study

OBJECTIVE: Lipoprotein lipase (LPL) and hepatic lipase (HL) are essential in hydrolysis of triglyceride-rich lipoproteins. LPL activity is negatively, whereas HL activity is positively, associated with total body fat. We determined the associations of trunk and leg fat mass with plasma LPL and HL activities in a cross-sectional study. RESEARCH METHODS AND PROCEDURES: LPL and HL activities were determined in post-heparin plasma in a sample of 197 men and 209 women, 60 to 87 years of age. A total body DXA scan was performed to determine trunk and leg fat mass. RESULTS: In women, but not in men, trunk fat mass was negatively associated with LPL activity, whereas leg fat mass was positively associated, after mutual adjustment and adjustment for age. Standardized betas (95% confidence interval) for trunk and leg fat mass were -0.24 (-0.41; -0.08) and 0.14 (-0.02; 0.31), respectively (interaction by sex, p = 0.03). Larger trunk fat mass was associated with higher HL activity in men [0.48 (0.28; 0.68)] and women [0.40 (0.24; 0.56)]. A negative association of leg fat mass and HL activity was observed in men, although not statistically significant [-0.13 (-0.33; 0.06)], and in women [-0.28 (-0.38; -0.18)]. DISCUSSION: Abdominal fat is associated with unfavorable and femoral fat with favorable LPL and HL activities in plasma.     

The classification of psychiatric disorder

Altogether 26 psychiatrists and other mental health workers, from Colombia, Brazil, Sudan, Egypt, India and the Philippines tried to reach agreement on the classification of 10 case histories, using the International Classification of Diseases (8th revision). The exercise was part of the WHO Collaborative Study on Strategies for Extending Mental Health Care. Conventions, mistakes, differences of opinion and a lack of rules are discussed as causes for disagreement.     

Crowding and subjective health in the Netherlands

Summary A random sample of the Dutch population was interviewed at home regarding life situation and health. The present analysis concerns only married respondents below 25 years, and all others in the sample, aged 25 years or more. Crowding (the number of people on a dwelling-unit divided by the number of rooms) appeared to be negligible as a factor associated with ill-health. Only respondents from larger households in more crowded quarters more often visited their general practitioner or resorted to psychotropic drugs more frequently.     

Chasing the dragon,related to the impaired lung function among heroin users

AIM: To describe the pulmonary function and prevalence of dyspnoea among methadone patients and to study the relation with exposure to heroin by inhaling. STUDY POPULATION: A sample of 100 patients from methadone maintenance treatment (84% male, average age 42 years). MEASUREMENTS: Questionnaires were used to measure life-time exposure to heroin, cocaine, cannabis, tobacco, and symptoms of dyspnoea. Spirometry was performed and residual difference of measured FEV(1) from the age, sex, height and ethnicity predicted value (delta FEV(1)) was used as a main outcome parameter. FINDINGS: The median delta FEV(1) was -0.26 l (inter quartile range -0.70; +0.12). Twenty per cent experienced dyspnoea while 'walking at a normal pace with someone of their own age'. History of cigarette smoking was reported by 98%; heroin smoking by 88%. Multiple linear regression analysis showed a statistically significant association between heroin-smoking and delta FEV(1), logistic regression analysis showed an association between heroin-smoking and prevalence of dyspnoea. CONCLUSIONS: Chronic heroin smoking seems to be related to an impaired lung function and higher prevalence of dyspnoea. However, part of the observed lung function impairment will be caused by tobacco smoking. Further research is needed to quantify the effect of heroin smoking and disentangle the effect of smoking heroin and tobacco.     

Microalbuminuria and Cardiovascular Autonomic Dysfunction Are Independently Associated With Cardiovascular Mortality: Evidence for Distinct Pathways: The Hoorn Study

OBJECTIVE

Microalbuminuria is associated with cardiovascular mortality, particularly among individuals with type 2 diabetes, but the mechanisms underlying this association are not completely understood. Microalbuminuria is known to be associated with cardiovascular autonomic dysfunction (C-AD), and C-AD in turn is associated with cardiovascular mortality. The purpose of this study, therefore, was to investigate whether C-AD can explain the relationship between microalbuminuria and cardiovascular mortality.

RESEARCH DESIGN AND METHODS

We studied 490 individuals from a population-based cohort of individuals aged 50–75 years who were followed for a median period of 13.6 years. Microalbuminuria was defined as an albumin-to-creatinine ratio ≥2.0 mg/mmol in an early-morning spot-urine sample. Ten parameters reflecting different aspects of cardiovascular autonomic function were measured and compiled into a total score of C-AD (mean of separate z scores). The association between C-AD and microalbuminuria was estimated by multiple linear regression, and relative risks (RRs) for cardiovascular mortality were estimated by Cox proportional hazards analyses.

RESULTS

After adjustments for age, sex, glucose tolerance status, and other risk factors, C-AD was associated with microalbuminuria (β = 0.16 [95% CI 0.01–0.33]), and both microalbuminuria (RR 2.09 [1.07–4.08]) and C-AD (1.74 [1.04–2.89]) were associated with cardiovascular mortality. These associations did not change after further mutual adjustment for C-AD (2.13 [1.09–4.17]) or microalbuminuria (1.76 [1.05–2.94]), respectively.

CONCLUSIONS

Both microalbuminuria and C-AD are independently associated with cardiovascular mortality, and the excess mortality attributable to microalbuminuria cannot be explained by C-AD.Microalbuminuria is associated with an increased risk of cardiovascular disease and mortality (1). This association is independent of other known cardiovascular risk factors such as hypertension, dyslipidemia, obesity, smoking, and impaired renal function (1,2). Several mechanisms, notably endothelial dysfunction and low-grade inflammation, have been proposed to explain, at least in part, the increased risk of cardiovascular mortality in individuals with microalbuminuria (3). Cardiovascular autonomic dysfunction (C-AD) could potentially constitute another such mechanism.Indeed, we as well as others have previously shown that C-AD is associated with microalbuminuria, especially in individuals with impaired glucose metabolism (IGM) and type 2 diabetes (4–6). Two proposed mechanisms explaining this association are, first, a disturbance in glomerular arteriolar autoregulation, which in turn may result in an inability to counteract glomerular hypertension (7), and, second, a reduced drop in nightly blood pressure due to C-AD, both of which may result in microalbuminuria (8). In addition, C-AD is associated with cardiovascular mortality (9,10) and can potentially link microalbuminuria to cardiovascular mortality by arrhythmogenic or atherogenic effects, for example, by promoting vascular calcification and arterial stiffness (11).In view of these considerations, we investigated, in a prospective cohort study, whether C-AD can explain the relationship between microalbuminuria and cardiovascular mortality or, alternatively, whether both microalbuminuria and C-AD are independently associated with cardiovascular mortality. These hypotheses have never been investigated in the general population and could have clinical relevance because the first hypothesis suggests that C-AD should be targeted to decrease mortality risk in individuals with microalbuminuria and, conversely, the second hypothesis suggests that both microalbuminuria and C-AD can be used for estimating the risk of cardiovascular mortality.