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Atherosclerosis. 2017 Aug;263:219-226. doi: 10.1016/j.atherosclerosis.2017.06.353. Epub 2017 Jun 21.

The inverse association of HDL-cholesterol with future risk of hypertension is not modified by its antioxidant constituent, paraoxonase-1: The PREVEND prospective cohort study.

Author information

1
School of Clinical Sciences, University of Bristol, Bristol, UK. Electronic address: skk31@cantab.net.
2
Department of Internal Medicine, University of Groningen and University Medical Center, Groningen, The Netherlands.
3
Department of Internal Medicine, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
4
Department of Endocrinology, University of Groningen and University Medical Center, Groningen, The Netherlands.

Abstract

BACKGROUND AND AIMS:

High-density lipoprotein cholesterol (HDL-C), an established risk marker for atherosclerotic cardiovascular disease (CVD), has been shown to be inversely and independently associated with incident hypertension. Paraoxonase-1 (PON-1) is an HDL-bound esterase enzyme associated with CVD, but its relationship with incident hypertension has not been previously investigated. We aimed at evaluating the prospective association between PON-1 and hypertension risk.

METHODS:

PON-1 arylesterase activity was measured in serum at baseline in 3988 participants without pre-existing hypertension in the Prevention of Renal and Vascular End-stage Disease (PREVEND) prospective population-based study. During a median follow-up of 10.7 years, 1206 participants developed hypertension.

RESULTS:

In age- and sex-adjusted analysis, the hazard ratio (95% CI) for incident hypertension per 1 standard deviation increase in PON-1 was 1.01 (0.96-1.07; p = 0.656), which remained non-significant after adjustment for several established hypertension risk factors and other potential confounders (0.99, 0.93 to 1.05; p = 0.764). The association was also non-existent on further adjustment for HDL-C (1.00 (0.94-1.06; p = 0.936)) and did not importantly vary across several clinical subgroups. In analyses in the same set of participants, HDL-C was continuously inversely and independently associated with hypertension risk; the association persisted after further adjustment for PON-1 activity and was not modified by PON-1 activity.

CONCLUSIONS:

In this Caucasian cohort of men and women, HDL-C, but not its anti-oxidant constituent - PON-1, is inversely, continuously and independently associated with future risk of hypertension. The association is independent of and not modified by PON-1.

KEYWORDS:

Antioxidant; HDL cholesterol; Hypertension; Paraoxonase-1; Risk factor

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