High HDL-C Could Increase Cardiovascular Disease Risk in Men with Hypertension

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Although high-density lipoprotein cholesterol (HDL-C) has gained a reputation as the “good cholesterol”, even being recognized as such on the US CDC website, new research from an analysis of nearly 12,00 patients in Southern Italy with more than 25,000 years of follow-up data suggests increased levels of HDL-C could signal a greater cardiovascular risk among men with hypertension.

Results of the study, which was conducted by a team from the University of Naples and Albert Einstein College of Medicine, detail a U-shaped association between HDL-C levels and cardiovascular, with a significantly increased risk of cardiovascular events observed in the low and high HDL-C groups compared to the medium HDL-C group, but investigators noted this risk could not be confirmed among female patients.

“In the algorithms currently used to calculate cardiovascular risk in the general population, HDL-C levels are considered protective. Our findings indicate that at high levels (ie, >80 mg/dL), this protective effect does not appear to hold true and, in fact, may confer an increased risk in male patients with hypertension,” wrote investigators, of the clinical implications of their study.

Spurred by recent research into the relationship between HDL-C and mortality risk, a team led by Bruno Timarco, MD, designed the current study citing a lack of data related to the relationship specifically among patients with hypertension. With his in mind, investigators designed their study with the intent of using multivariable logistic regression analyses to estate the effects of HDL-C on cardiovascular events and a spline analysis to assess the association between HDL-C on risk of cardiovascular events, with a 2-tailed P <.05 considered statistically significant.

An open electronic registry of community hospital-based hypertension clinics and general practitioners from the Campania region in Southern Italy, the Camapnia Salutre Network included data from 14,161 patients at the time of extraction. Limiting their analysis to adult patients with a confirmed diagnosis of hypertension, at least 1 follow-up visit, and without a history of prevalent coronary/cerebrovascular disease, atrial fibrillation, or valvular heart disease, investigators identified a cohort of 11,987 individuals for inclusion in their analyses.

The HDL-C levels used to stratify the patients into 4 groups were defined as less than 40 mg/dL, 40-80 mg/dL, and greater than 80 mg/dL. Of the 11,976 patients included in the study, 2674, 9060, and 53 patients were placed into the low, medium, and high HDL-C groups, respectively. Investigators pointed out the mean HDL-C plasma concentration in women was significantly higher than in men (54.4±13.3 vs 47.28±11.9; P <.0001), with the percentage of female patients in the high HDL-C group 3 times greater than the percentage of men.

In adjusted analyses, investigators identified a total of 245 cardiovascular events in the study cohort, noting hazard ratios of 3.5% in the high HDL-C group, 3.4% in the low HDL-C group (P <.08), and 2.6% in the medium HDL-C group (P=.02 vs low and high HDL-C groups). In their spline analysis, investigators observed a U-shaped association between HDL-C levels and cardiovascular outcomes. Investigators highlighted the association of high HDL-C with increased cardiovascular risk was not observed for women in the logistic regression or spline analysis.

“Taken together, our data indicate that levels of HDL-C >80 mg/dL increase cardiovascular risk in male patients with hypertension. Therefore, we recommend to opportunely revise the algorithms currently used for the calculation of the cardiovascular risk; based on the results of the present study, physicians should manage dyslipidemia in hypertensive patients cum grano salis,” investigators added.

This study, “High HDL (High-Density Lipoprotein) Cholesterol Increases Cardiovascular Risk in Hypertensive Patients,” was published in Hypertension.

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