Early impairment of left ventricular function in hypercholesterolemia and its reversibility after short term treatment with rosuvastatin: A preliminary echocardiographic study
Introduction
Although hypercholesterolemia is a well known risk factor for atherosclerosis, in recent years clinical observations and animal models suggest a role of cholesterol on ventricular function independently of coronary artery disease (CAD). For example, hypercholesterolemia may induce electrical remodeling of the heart, with prolongation of the action potential and QTc interval, increase in repolarization dispersion and vulnerability to ventricular fibrillation [1], as well as reduced heart rate variability in men with or without CAD [2]. In animal models elevated serum cholesterol has been linked to both systolic and diastolic cardiac dysfunction (decreased maximal shortening rate, increased time to peak velocity, decreased relaxation rate, reduction in maximum contractile function and longer systolic contraction time) [3], [4]. Moreover, hypercholesterolemia seems to impair left ventricular response to dobutamine stress by decreasing coronary flow reserve and reducing capillary density [5]. On the other hand, the reduction of cholesterol levels with statins attenuates adverse left ventricular remodeling in patients with non ischemic heart failure [6], improves left ventricular function in rabbits post myocardial infarction [7].
Echocardiographic techniques have been used to study the consequences of hypercholesterolemia on cardiac function. Salmasi et al. [8] found no significant difference in E/A ratio measured by pulsed wave Doppler between hypercholesterolemic subjects and controls at rest, but a significantly lower E/A ratio at peak isometric exercise in the patient group. Recently, the effect of statins-therapy on left ventricular function has been evaluated by tissue Doppler imaging [9]. This study showed that systolic function at rest did not improve after atorvastatin, although there was a trend towards an increase in systolic velocity and improvement of myocardial reserve through low dose dobutamine stress imaging. In addition, patients treated with atorvastatin presented a trend towards the increase of early and (no significant) late diastolic velocity after 6 months of therapy, even though the E/A ratio remained unchanged.
The aims of the present study were: (1) to study ventricular functional and structural abnormalities in patients with hypercholesterolemia, free of overt heart disease, by using conventional echocardiography in association with the study of myocardial performance index (Tei index) and by relatively new ultrasonic techniques such as integrated backscatter (IBS) [10] (which permits evaluation of intrinsic contractility and tissue characterization) and color Doppler myocardial imaging (CDMI) [11], [12] (for the analysis of regional myocardial strain and strain rate) and (2) to verify the effect of rosuvastatin on these abnormalities, evaluated with the same ultrasonic methodology.
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Study population
Thirty three patients with hypercholesterolemia (HC) were recruited at the Lipids Clinic at the University Hospital of Pisa (Table 1). Twenty-five aged-matched healthy volunteers (38.74 ± 5.3 years versus HC 43.9 ± 10.2 years; p: ns.), randomly recruited among members staff of our cardiac unit, were considered as control group (C).
After the secondary causes for hypercholesterolemia (e.g., hypothyroidism, nephrotic syndrome, dysproteinemias, diabetes mellitus, and obstructive liver disease) have
Biochemistry
Blood samples were obtained after a 10–12 h overnight fasting. Serum total (TC), and high density lipoprotein (HDL-C) cholesterol and triglyceride (TG) concentrations were measured by standard methods on an automatic analyzer (ModularRoche Diagnostic, Germany). LDL cholesterol (LDL-C) was calculated according to the Friedewald formula.
Echocardiographic analysis
In the two times of observation all the patients and controls were submitted to conventional echocardiography, pulsed wave tissue Doppler imaging (PWTDI), color
Study population
Clinical and biochemical characteristics of HC patients and controls are reported in Table 1. The levels of TC and LDL-C were significantly higher in patients with HC than in controls (respectively TC: 327 ± 54 mg/dl versus 184 ± 12 mg/dl, p < 0.0001 and LDL-C: 254 ± 61 mg/dl versus 136 ± 7 mg/dl, p < 0.0001), while HDL-C concentrations were lower (58 ± 15 mg/dl versus 67 ± 10 mg/dl, p < 0.009). Body mass index was slightly but significantly lower in controls (22.8 ± 2.5 kg/m2) in comparison with HC patients (25.8 ± 4.3; p <
Discussion
The main findings of this study were: (1) the presence in patients with hypercholesterolemia without evidence CAD of very early subclinical myocardial abnormalities relative to the longitudinal global systolic and diastolic function as shown by PW-Tissue Doppler and myocardial Performance Index (Tei index); (2) the presence in HC of myocardial intrinsic contractility impairment as showed by IBS (CVI) alterations; (3) the significant correlation between the extent of functional impairment of the
Conclusion
The hypercholesterolemia seems to determine, still before atherosclerosis development, an “Hypercholesterolemic Cardiomyopathy” that could produce the physiopathological substratum for an “impaired preconditioning” when eventually an acute coronary syndrome happens. These functional myocardial abnormalities related to cholesterolemic level could be normalized by early treatment with rosuvastatin. It could be interesting to know if all types of statins have the same effects of rosuvastatin on
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