Interplay Between Statins, Cav1 (Caveolin-1), and Aldosterone

Hypertension. 2020 Sep;76(3):962-967. doi: 10.1161/HYPERTENSIONAHA.120.14777. Epub 2020 Aug 3.

Abstract

Statin use is associated with lower aldosterone levels. We hypothesized that caveolin-1 may be important for the uptake of statins into the adrenal gland and would affect statin's aldosterone-lowering effects. The aim of this study was to test whether the caveolin-1 risk allele (rs926198) would affect aldosterone levels associated with statin use. The Hypertensive Pathotype database includes healthy and hypertensive individuals who have undergone assessment of adrenal hormones. Individuals were studied off antihypertensive medications but were maintained on statins if prescribed by their personal physician. Adrenal hormones were measured at baseline and after 1 hour of angiotensin II stimulation on both high- and low-sodium diets. A mixed-model repeated-measures analysis was employed with a priori selected covariates of age, sex, body mass index, and protocol (low versus high sodium, baseline versus angiotensin II stimulated aldosterone). A total of 250 individuals were included in the study; 31 individuals were taking statins (12.4%) and 219 were not. Among statin users, carrying a caveolin-1 risk allele resulted in a 25% (95% CI, 1-43.2) lower aldosterone level (P=0.04). However, among nonstatin users, carrying a caveolin-1 risk allele resulted in no significant effect on aldosterone levels (P=0.38). Additionally, the interaction between caveolin-1 risk allele and statin use on aldosterone levels was significant (P=0.03). These findings suggest caveolin-1 risk allele carrying individuals are likely to receive the most benefit from statin's aldosterone-lowering properties; however, due to the observational nature of this study, these findings need further investigation.

Keywords: aldosterone; alleles; cardiovascular disease; caveolin-1; hypertension.

Publication types

  • Observational Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Glands* / drug effects
  • Adrenal Glands* / metabolism
  • Aldosterone / metabolism*
  • Angiotensin II / pharmacology
  • Caveolin 1* / genetics
  • Caveolin 1* / metabolism
  • Cholesterol / metabolism
  • Correlation of Data
  • Dyslipidemias* / drug therapy
  • Dyslipidemias* / genetics
  • Female
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology*
  • Hypertension / metabolism*
  • Male
  • Pharmacogenomic Testing / methods
  • Pharmacogenomic Testing / statistics & numerical data
  • Pharmacogenomic Variants
  • Polymorphism, Single Nucleotide

Substances

  • CAV1 protein, human
  • Caveolin 1
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Angiotensin II
  • Aldosterone
  • Cholesterol