MSI Newsletter - May 2007

The Metabolic Syndrome amplifies hypertension-related cardiac and renal changes

Target organ damage may explain the enhanced cardiovascular risk associated with the Metabolic Syndrome.

The increased cardiovascular risk associated with the metabolic syndrome in patients with hypertension may be partly mediated by preclinical end-organ damage. This study sought to evaluate the influence of the metabolic syndrome on some cardiac, renal, and retinal markers of target organ impairment.

Mulè G, Nardi E, Cottone P, et al. Influence of metabolic syndrome on hypertensionrelated target organ damage. J Intern Med 2005;257: 503-13.

Hypertension is frequently associated with metabolic abnormalities that are key features of the metabolic syndrome, such as dyslipidaemia, abdominal obesity, elevated plasma glucose, and insulin resistance. In this study, Mulè et al investigated the effect of metabolic syndrome on markers of target organ damage. They used the working definition of metabolic syndrome given in the Third Report of the National Cholesterol Education Program ( NCEP ) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (ATP III).

Study population

The study population was selected from 478 hypertensive patients without diabetes mellitus consecutively attending the authors' hypertension center. Most were referred for specialist advice by their general practitioners. Eighty subjects were not included because of secondary or malignant hypertension, heart failure, positive history or clinical signs of ischaemic heart disease, cerebrovascular disease, renal insufficiency (serum creatinine >133 µmol/L [1.5 mg/dL] in men and >124 µmol/L [1.4 mg/dL] in women), proteinuria, major noncardiovascular (CV) diseases, dyslipidaemia requiring pharmacological treatment, and known diabetes or fasting blood glucose =126 mg/dL. Of the remaining subjects, 45 were also excluded because of suboptimal echocardiographic traces (39 subjects) or unreliable urine collection (6 patients), so the final statistical analysis involved 353 patients.

Study design and measurements

A clinical history was taken and a physical examination performed in all cases. After drug washout, body weight, height, waist circumference, and blood pressure were measured. Urinalysis was performed and a 24-h urine sample was collected to evaluate creatinine clearance and albumin excretion rate ( AER ). Microalbuminuria was assessed by radioimmunoassay and defined as AER =20 µg/min (normal AER <20 µg/min). Routine blood chemistry was performed. Patients underwent 24h ambulatory blood pressure monitoring ( ABPM ) and two-dimensional M-mode echocardiography. The ocular fundus was examined by bilateral, nonmydriatic retinography. Left ventricular ( LV ) mass was determined using a standard formula and indexed by body surface area (LVMI) and by height (LVMH), to allow for obesity. LV hypertrophy was defined as LVMI =125 g/m-2 for men and LVMI =110 g/m-2 for women and as LVMH =49.2 g/m-2.7 for men and LVMI =46.7 g/m-2.7 for women.

Results

The overall prevalence of metabolic syndrome was 37%. Participants with metabolic syndrome exhibited significantly higher LV chamber diameter, posterior wall and interventricular septum thickness, relative wall thickness, left atrial size, LV mass, normalized either for body surface area or for height, even after controlling for age, gender, 24-h blood pressures and duration of hypertension. The likelihood of LV hypertrophy was 2.89-fold higher (95% confidence interval: 1.68-4.98) in the metabolic syndrome group. LV mass was higher in subjects with metabolic syndrome, after adjustment for age, sex, duration of hypertension, previous antihypertensive therapy, 24-systolic and diastolic blood pressures and each individual component of metabolic syndrome (blood glucose, HDL-C, triglycerides, and waist circumference). The relationship between metabolic syndrome and LV mass was confirmed in multivariate regression models including metabolic syndrome together with its individual components, as independent variables. This suggests that metabolic syndrome may have a deleterious effect on cardiac structure over and above the potential contribution of each component of this syndrome, and that the cluster of abnormalities that comprise metabolic syndrome may have a synergistic negative impact on LV mass.

Higher AER and so a greater prevalence of microalbuminuria, and higher age-adjusted creatinine clearance values were observed in hypertensive subjects with metabolic syndrome, in comparison with those without metabolic syndrome. The main predictors of microalbuminuria were blood pressure and glucose levels.

Thus, the enhanced CV risk associated with metabolic syndrome may be partly mediated through an increased prevalence of preclinical CV and renal changes in patients with essential hypertension and metabolic syndrome. There was an increased prevalence of grade I and grade II hypertensive retinopathy in subjects with metabolic syndrome. The prognostic significance of this finding is unclear, because data are inconsistent on the association between the first two degrees of hypertensive retinopathy and CV outcomes.

Figure : Prevalence of markers of preclinical cardiac, renal, and retinal damage in patients with and without metabolic syndrome.

Conclusion

The main finding was the identification of a close association between metabolic syndrome ( NCEP -ATP III criteria) and some indices of preclinical cardiac, renal, and retinal damage. As the study was of cross-sectional design, the authors are only able to hypothesize about the association of metabolic syndrome with cardiac hypertrophy, which might, for example, be explained by insulin resistance and the accompanying compensatory hyperinsulinemia, which are key pathophysiological features of metabolic syndrome. Nevertheless, metabolic syndrome seems to amplify hypertension-related cardiac and renal changes, over and above the potential contribution of each single component of this syndrome. As these markers of target organ damage are well-known predictors of CV events, the findings of this study may partly explain the enhanced CV risk associated with metabolic syndrome.

Central obesity as an “optional” component identifies more individuals at risk of ischaemic heart disease

Central obesity is an "essential" component of the metabolic syndrome in the definition of the International Diabetes Federation (IDF) but an "optional" in that of the American Heart Association/National Heart, Lung, and Blood Institute (AHA/NHLBI). To examine the effect of the metabolic syndrome with or without central obesity in an Asian population with ischaemic heart disease (IHD), 4334 healthy subjects from a population-based cohort study were classified according to the presence or absence of the metabolic syndrome and central obesity and followed up for an average of 9.6 years. The prevalence of the metabolic syndrome was 17.7% by the IDF criteria and 26.2% by the AHA/NHLBI criteria. Cox's proportional hazards model revealed that compared to subjects without metabolic syndrome, subjects with central obesity/metabolic syndrome and those with no central obesity/metabolic syndrome were at significantly increased risk of IHD, the adjusted hazard ratios for risk of a first IHD being 2.8 (95% CI, 1.8-4.2) and 2.5 (95% CI, 1.5-4.0) respectively. In conclusion, the presence of the metabolic syndrome with or without central obesity conferred an increased risk of IHD. Having central obesity defined using updated Asian waist circumference cutoff points as an "optional" rather than "essential" criterion to define the metabolic syndrome actually identified more subjects at risk of developing IHD in later life.

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Metabolic syndrome shown to be an independent predictor of arterial stiffness

Metabolic syndrome has been linked to arterial stiffness and cardiovascular disease. It is not established whether this association relates to the syndrome itself or to the sum of its cardiovascular components. A total of 401 Finnish men and women aged =45 years were included in this study aimed to examine the independent influences of metabolic syndrome, its components, and other cardiovascular risk factors on arterial stiffness. As a marker of elevated arterial stiffness, pulse wave velocity (PWV) measured by whole-body impedance cardiography was used. According to the results, the two definitions of the metabolic syndrome used in this research - National Cholesterol Education Program and International Diabetes Federation - did not differ in their ability to identify subjects with increased arterial stiffness. Multivariate analysis revealed that the metabolic syndrome was independently associated with increased arterial stiffness independently of other known cardiovascular risk factors. Furthermore, systolic blood pressure, age, waist circumference, and fasting blood glucose increased arterial stiffness independently of other known cardiovascular risk factors.

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Highest prevalences of metabolic syndrome in Pacific people and Maori within a multicultural population in Auckland

In a cross-sectional survey of 35-74 year-old adults within the Auckland area, including 1006 Maori, 996 non-Maori Pacific people, and 2020 of other ethnicity (mainly white Caucasians of European ancestry; Others), the prevalences of the metabolic syndrome (ATP III criteria) were 39%, 32% and 16% among Pacific people, Maori and other ethnicities, respectively. Pacific people were two and a half times as likely as Others and Maori people were twice as likely as Others to have the metabolic syndrome. After adjustment for each of the components of the metabolic syndrome, these ethnic differences could mainly be accounted for by differences in obesity.

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Visceral fat tissue expansion and adipokine secretion associated with systemic inflammation in obese subjects

To evaluate the hypothesis that excess visceral fat tissue promotes systemic inflammation by secreting inflammatory adipokines into the portal circulation, adipokine arteriovenous concentration differences across visceral fat tissue were assessed by obtaining portal vein and radial artery blood samples during gastric bypass surgery in 25 extremely obese subjects. Mean plasma IL-6 concentration was approximately 50% higher and mean plasma leptin concentration approximately 20% lower in portal vein than in radial artery (P=0.007 and P=0.0002, respectively) in these obese subjects, portal vein IL-6 concentration being directly correlated with systemic C-reactive protein concentration (P=0.005), an acute phase reactant whose hepatic synthesis may be mediated by IL-6. Visceral fat tissue expansion thus appears to be an important site for IL-6 secretion and this may explain the potential mechanistic link between visceral fat tissue expansion and systemic inflammation in subjects with abdominal obesity.

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76th Annual European Atherosclerosis Society

Date:

June 10-13, 2007

Location:

Helsinki, Finland

Website:

http://www.eas2007.fi/

American Diabetes Association

Date:

June 22-26, 2007

Location: