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.

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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.