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J Clin Hypertens (Greenwich). 2011;13:710–715. ©2011 Wiley Periodicals, Inc.
The authors investigated whether high-density lipoprotein (HDL) cholesterol plays a role in arterial stiffening and left diastolic dysfunction in essential hypertension. Carotid arterial stiffness parameter and left ventricular (LV) diastolic function index were evaluated in 217 patients with essential hypertension. The correlations of dyslipidemia, especially low HDL cholesterol, to LV diastolic function and arterial stiffness were investigated in these patients. Arterial stiffness parameter increased with the increasing of E/Em (LV diastolic function index: the ratio of transmitral peak velocity of early filling to peak early diastolic motion velocity of mitral annulus) (r=0.26, P<.01). In univariate regression analysis, HDL cholesterol was inversely associated with arterial stiffness parameter and E/Em (r=−0.23 and r=−0.27, respectively, P<.01). The association of HDL cholesterol with arterial stiffness and LV diastolic function was observed in both men and women. Triglycerides were weakly correlated with arterial stiffness parameter and E/Em, while low-density lipoprotein and total cholesterol were not. In multiple regression analysis, only low HDL cholesterol was found as an independent predictor for both arterial stiffness and LV diastolic dysfunction. Enhanced arterial stiffness is associated with LV diastolic dysfunction. Low HDL cholesterol may lead to the deterioration of both arterial stiffness and LV diastolic function in patients with essential hypertension.
Both left ventricular (LV) diastolic dysfunction and arterial stiffening, which are common cardiovascular consequences of hypertension, are independent risk factors for cardiovascular morbidity and mortality.1,2
Many well-known risk factors for diastolic dysfunction, such as hypertension, advanced age, and atherosclerosis, are also associated with an increase in arterial stiffness.3 These could prompt an etiologically homologous disease of artery and myocardium. Some studies have defined the association between arterial stiffness and ventricular structural or functional effects.4,5 However, the common mechanism of ventricular-vascular stiffness is still unclear.
While abnormalities in glucose and insulin metabolism have been found to accelerate the deterioration of arterial stiffness and LV diastolic function,6,7 dyslipidemia is also the metabolic abnormality observed most frequently in hypertensive patients. However, the influence of serum lipids on both arterial stiffness and ischemia-independent cardiac functional changes is still not fully elucidated.8 In the presented study, the major aim was to investigate the correlation of dyslipidemia, especially low high-density lipoprotein (HDL) cholesterol, to arterial stiffness and LV diastolic function in patients with essential hypertension.
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The presented study showed that the development of LV diastolic dysfunction was accompanied by enhanced arterial stiffness. Metabolic factors may be involved in the progress of both LV diastolic dysfunction and arterial stiffening. Consistent with recent studies,12–14 low HDL cholesterol instead of total or LDL cholesterol was independently associated with arterial stiffening and LV diastolic dysfunction. While ventricular-vascular structural and functional changes are increased by normal aging, the presence of cardiovascular risk factors accelerates their changes.15 Stiffening in both medium and large elastic arteries is associated with multiple cardiovascular risk factors, including hypertension, dyslipidemia, obesity, smoking, diabetes, and aging, all of which have also promoted the development of atherosclerosis in previous studies.15,16
The relationship between arterial stiffness and HDL cholesterol levels has been reported only indirectly in some studies. Ferrier and colleagues17 reported that atorvastatin treatment reduced artery stiffness in patients with isolated systolic hypertension accompanied with increased HDL cholesterol and reduced total and LDL cholesterol. Moreover, cholesterol-lowering therapy was efficacious in reducing arterial stiffness in patients with hypercholesterolemia.18 Brouwers and colleagues19 studied patients with familial combined hyperlipidemia and found that they had increased arterial stiffness compared with controls. In our study, the significant association of HDL cholesterol with arterial stiffness was observed not only in women but also in men by univariate and multivariate regression analysis.
E/Em and E/Am, which usually reflect LV filling pressure by echocardiographic technology, were used as diastolic function in our study. LV isovolumic relaxation time starts from aortic valve closing to mitral valve opening, which is a process of initiative and energy consumption. The insufficiency of LV relaxation would delay the start of diastolic filling. LV filling pressure increases in proportion to diastolic function and decreases in early and middle diastolic dysfunction. Severe diastolic dysfunction involves myocardial fibrosis and passive filling limitation. When the increasing LV filling pressure was followed by the compensatory left atrial expansion and high pulmonary pressure, LV filling pressures could not be used as an index of diastolic dysfunction. Patients in this study came from the same community and were also in stable condition. In addition, these hypertensive patients did not have severe diastolic dysfunction on echocardiographic examination; therefore, their LV filling pressure accurately reflected their LV diastolic function.
While impaired LV diastolic relaxation is another common cardiac change observed in hypertensive patients, some significant metabolic factors, which are independent of BP and LV mass index, have been associated with this diastolic dysfunction.20 In fact, abnormalities in glucose and insulin metabolism have been shown to accelerate the deterioration of arterial stiffness and LV diastolic function.6,7 Dyslipidemia is one of metabolic abnormalities. Nonetheless, the correlation between serum lipids and LV diastolic function in essential hypertension was limited. Similar with Horio and colleagues’ study,21 our findings suggest that only low HDL cholesterol may pose an independent adverse effect on LV diastolic function in hypertensive patients independently of age, sex, BMI, smoking status, BP, total cholesterol, LDL cholesterol, triglycerides, glucose, LV mass index, heart rate, and arterial stiffness. Furthermore, Mizuguchi and associates reported that statin therapy could promote LV diastolic function accompanied with the improvement of blood lipid level, which is consistent with our findings.22
Our study showed that total and LDL cholesterol had no significant association with impairments of LV diastolic relaxation and arterial stiffness. Brinkley and colleagues believe that plasma oxidized LDL levels (ox-LDL, a marker of oxidative stress), a key player in the pathogenesis of atherosclerosis, might also play a role in arterial stiffening.23 In addition, Rietzschel and coworkers proved that ox-LDL cholesterol was associated with decreases in cardiac function and also a risk marker for early ventricular remodeling independently of vascular alterations.24 Ox-LDL cholesterol may be one of the key points in our future research.
In the present study, triglyceride levels showed a weak correlation with arterial stiffness and LV diastolic function, although total and LDL cholesterol did not at all. In addition, arterial stiffening and LV diastolic dysfunction were most advanced in a subgroup with both low HDL cholesterol and high triglycerides. Individuals in this group also had increased BMI, plasma glucose level, and diastolic BP, all of which appeared to be associated with the metabolic syndrome, a cluster of multiple interrelated abnormalities in lipid and glucose metabolism along with hypertension and obesity.25,26 Therefore, the influence of triglycerides was considered only as a part of multiple interrelated metabolic factors.
Clinical Implications and Potential Limitations
Because arterial stiffness may be modifiable,27 HDL cholesterol might be a potential target for intervention in our future study of diastolic heart failure. HDL cholesterol, as one of complex metabolic factors, has an important role in this “heart-vessel coupling disease,”28 but the exact mechanism needs to be explored further. The limitation of the present study lies in its purely cross-sectional design. We performed only association analysis, but long-term follow-up of our patients would be needed to corroborate the proposed value of HDL cholesterol in predicting arterial stiffness and LV diastolic function.