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. 2022 Oct;79(10):2355-2363.
doi: 10.1161/HYPERTENSIONAHA.122.19912. Epub 2022 Aug 15.

High HDL (High-Density Lipoprotein) Cholesterol Increases Cardiovascular Risk in Hypertensive Patients

Valentina Trimarco  1 , Raffaele Izzo  2 , Carmine Morisco  2   3 , Pasquale Mone  4   5 , Maria Virginia Manzi  2 , Angela Falco  1 , Daniela Pacella  6 , Paola Gallo  2 , Maria Lembo  2 , Gaetano Santulli  2   3   4   7   5 , Bruno Trimarco  2   3
Affiliations

High HDL (High-Density Lipoprotein) Cholesterol Increases Cardiovascular Risk in Hypertensive Patients

Valentina Trimarco et al. Hypertension. 2022 Oct.

Abstract

Background: Emerging evidence suggests that elevated circulating levels of HDL-C (high-density lipoprotein cholesterol) could be linked to an increased mortality risk. However, to the best of our knowledge, the relationship between HDL-C and specific cardiovascular events has never been investigated in patients with hypertension.

Methods: To fill this knowledge gap, we analyzed the relationship between HDL-C levels and cardiovascular events in hypertensive patients within the Campania Salute Network in Southern Italy.

Results: We studied 11 987 patients with hypertension, who were followed for 25 534 person-years. Our population was divided in 3 groups according to the HDL-C plasma levels: HDL-C<40 mg/dL (low HDL-C); HDL-C between 40 and 80 mg/dL (medium HDL-C); and HDL-C>80 mg/dL (high HDL-C). At the follow-up analysis, adjusting for potential confounders, we observed a total of 245 cardiovascular events with a significantly increased risk of cardiovascular events in the low HDL-C group and in the high HDL-C arm compared with the medium HDL-C group. The spline analysis revealed a nonlinear U-shaped association between HDL-C levels and cardiovascular outcomes. Interestingly, the increased cardiovascular risk associated with high HDL-C was not confirmed in female patients.

Conclusions: Our data demonstrate that there is a U-shaped association between HDL-C and the risk of cardiovascular events in male patients with hypertension.

Keywords: cholesterol; dyslipidemias; heart disease risk factors; hydroxymethylglutaryl-CoA reductase inhibitors; hypercholesterolemia; population; sex characteristics.

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Figures

Figure 1.
Figure 1.. Flow chart of the study.
CV indicates cardiovascular; and HDL-C, high-density lipoprotein cholesterol.
Figure 2.
Figure 2.. Cardiovascular risk is increased by both low HDL-C (high-density lipoprotein cholesterol) and high HDL-C.
Risk of cardiovascular (CV) events in our population divided in 3 groups according to the HDL-C levels.
Figure 3.
Figure 3.. A U-shaped association links HDL-C (high-density lipoprotein cholesterol) and the risk of cardiovascular events in patients with hypertension.
Spline plot showing the U-shaped association between HDL-C and risk of cardiovascular events. The shaded area represents the 95% CI. The blue dashed line indicates the HDL-C reference value at 40 mg/dL. HR indicates hazard ratio.
Figure 4.
Figure 4.. Female patients with hypertension do not exhibit a U-shaped association between HDL-C (high-density lipoprotein cholesterol) and the risk of cardiovascular events.
Spline plots showing the association between HDL-C and risk of cardiovascular events in female (A) and male (B) patients with hypertension. The shaded area represents the 95% CI. The blue dashed line indicates the HDL-C reference value at 40 mg/dL. HR indicates hazard ratio.
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