The present study evaluated echocardiographic measurements of LV geometry and function, IMT and PWV assessment of arterial stiffness in a cross sectional cohort of subjects grouped according to the number of MetS criteria present. This study clearly demonstrated a sex specific relationship between MetS and cardiovascular function and geometry. The fact that the ANCOVA model was used reduces the likelihood that this finding was an artifact of covariance (age, BP, or smoking). In females, we found that: 1) LVEF, which reflects LV systolic function, was within normal limits in all three groups, 2) RWT results were similar in all three groups, while LV mass and LV mass/height2.7 increased progressively across the three groups, 3) E/A and deceleration time, which reflects LV diastolic function, showed progressive impairment across the three groups after adjustment for age and BP, and 4) aortic PWV increased progressively across the three groups after adjustment for age, BP and smoking status. In males, no differences were found across the three groups, except in LA volume index and IMT. The results of this study suggest that an increase in the number of MetS criteria is associated, in an independent manner, with subclinical eccentric LV hypertrophy, diastolic dysfunction, and increased arterial stiffness, irrespective of age and BP. The effects of MetS were found to be pronounced in females, but not in males. These findings did not change when subjects with diabetes and hypertension were excluded (data not shown). When LV mass was indexed for body surface area (a normalization that minimizes the effect of obesity since body weight is included in its computation), metabolic risk factors showed no significant effects. This finding strongly confirms that obesity, when present, is the feature that tracks the cumulative effect of the other risk factors (hypercholesterolemia and diabetes).
Although several recent studies have reported impaired LV diastolic function in MetS patients, consensus is still lacking on the effect of MetS on cardiac function and geometry. In the Strong Heart Study, MetS was found to be associated with reduced LV systolic and diastolic function and LV dimensions, while LV mass and RWT were found to be higher in the MetS group (17
). In contrast, Grandi et al. (18
) found that only LV diastolic function was reduced in MetS, and that LV systolic function was normal in clinically hypertensive non-diabetic subjects. They also reported that both LV mass and relative wall thickness were significantly increased in the MetS group, but that LV dimensions were similar in both groups. Mule et al. (19
) reported that MetS has a deleterious effect on hypertension-related target organ damage. They observed increased LV mass, RWT, and deceleration times in hypertensive subjects with MetS compared with a hypertensive cohort without MetS. In a population-based study, Sundst-rom et al. (20
) demonstrated a strong correlation between MetS and left ventricular mass and relative wall thickness, a correlation which was independent of blood pressure status. Only a few previous studies of the impact of MetS on LV mass have conducted separate analyses for males and females, and these studies have reported conflicting findings. Schillaci et al. (21
) found that MetS had a more pronounced effect on LV hypertrophy and function in females. Our results support the hypothesis that MetS is associated with LV diastolic dysfunction in females only, even in subjects without LV systolic dysfunction, and irrespective of BP status. However, in the present study, changes in LV geometry tended toward eccentric hypertrophy, and waist circumference was found to have the most significant effect on left ventricular functional and geometric change.
In the present study, MetS was associated with increased carotid IMT and aortic PWV, and this effect was independent of age, BP, and smoking status, particularly in females. In females, hrPWV and faPWV showed a tendency to increase in a stepwise manner across the three groups, but these differences did not achieve statistical significance. This suggests that the cluster of MetS components may interact synergistically to increase arterial stiffness, particularly in females. Several previous studies have reported that the grouping of insulin resistance syndrome components is associated with excessive carotid IMT, beyond a level attributable to an additive effect, and that MetS was independently associated with carotid IMT and arterial stiffness (22
). However, most of the studies that have investigated associations with MetS and its components have focused on one specific arterial segment, such as the aorta, brachial-ankle segment, or the lower limb, or alternatively, one arterial site such as the brachial and (more frequently) the carotid artery, and their results have been conflicting. There have been few studies of sex-specific MetS effects on arterial stiffness. Schillaci et al. (24
) demonstrated that MetS was independently associated with higher aortic velocity, but not with higher upper limb pulse wave velocity. Ferreira et al. (25
) reported that stiffness in the femoral arteries was higher than that in the carotid arteries. Other studies have evaluated central and peripheral arterial segments and reported that MetS is associated with increased central and peripheral arterial stiffness in females (26
). The present study showed an association between MetS and aortic PWV in females, but these findings did not reach statistical significance. Further studies are required to demonstrate the relative impact of MetS on PWV in differing arterial regions.
The mechanism underlying the influence of sex on the association between MetS and LV geometry and function, arterial stiffness, and structural change remains unknown. It will be necessary to conduct further studies in order to elucidate the nature of this sex-specific effect.
The present study has important limitations. Its cross-sectional design precludes the performance of outcome analyses. The sample size was relatively small, especially for the group with no MetS components. Ambulatory BP measurements, which have been shown to be more predictive of hypertensive end-organ damage, were not performed. Although PWV may vary according to the time of day, these variables were consistently measured in the morning.
In conclusion, clustering of MetS components is independently associated with subclinical eccentric LV hypertrophy, diastolic dysfunction, and increased aortic wall stiffness, particularly in females, irrespective of age and BP status. Waist circumference has the most powerful influence on LV geometry and function and IMT.