Recent studies have yielded controversial results on the long-term effects of statins on the risk of cardiovascular (CV) events. To fill this knowledge gap, we assessed the relationship between low-density lipoprotein cholesterol (LDL-C) levels and CV events in hypertensive patients without previous CV events and naïve to antidyslipidemic treatment within the “Campania Salute Network” in Southern Italy. We studied 725 hypertensive patients with a mean follow-up of 85.4 ± 25.7 months. We stratified our cohort into three groups based on LDL cholesterol (LDL-C) levels in mg/dl: group 1) patients showing during the follow-up a mean LDL-C value ≤100 mg/dl in absence of statin therapy; group 2) statin-treated patients with LDL ≤100 mg/dl; and group 3) patients with LDL-C >100 mg/dl. No significant difference among the groups was observed in terms of demographic and clinical characteristics and medications. The incidence of first CV events was 5.7% in group 1, 6.0% in group 2, and 11.9% in group 3 (P < 0.05 vs. group 1 and group 2). A stable long-term satisfactory control of LDL-C plasma concentration (≤100 mg/dl) reduced the incidence of major CV events from one event every 58.6 patients per year to one event every 115.9 patients per year. These findings were confirmed in a Cox regression analysis, adjusting for potential confounding factors. Collectively, our data demonstrate that a 7-year stable control of LDL-C reduces the incidence of CV events by 40%.

SIGNIFICANCE STATEMENT There are several discrepancies between Mendelian studies and other investigations concerning the actual effects of reduction of plasma concentration of low-density lipoprotein (LDL) cholesterol on the incidence of major cardiovascular events. Taken together, our data in nondiabetic subjects show that a 7-year stable control of LDL cholesterol induces a ∼40% reduction of the incidence of cardiovascular events.

The Santulli’s Laboratory is currently supported in part by National Institutes of Health National Heart, Lung, and Blood Institute [Grants R01-HL146691, R01-HL159062, R01-HL164772, and T32-HL144456] and National Institute of Diabetes and Digestive and Kidney Diseases [Grants R01-DK123259 and R01-DK033823] (to G.S.); by the Diabetes Action Research and Education Foundation (to G.S.); by the Waxman Research Foundation (to G.S.); and by the Irma T. Hirschl and Monique Weill-Caulier Trusts (to G.S.). The study was also supported by [Grant 00014Prin-2017 ID43237] (to V.T.) and by [Grant PNRR-POC-2022-12376833: New multimodal CArdioREspiratory MOnitoring DEvice to improve chronic patient management (CARE-MODE)] (to R.I.).

The authors declare that they have no conflicts of interest with the contents of this article.

↵1 V.T. and R.I. share the first authorship.

↵1 G.S. and B.T. share the senior authorship.

dx.doi.org/10.1124/jpet.123.001878.