Impact of Atorvastatin Treatment in First‐Degree Relatives of Patients With Premature Coronary Artery Disease With Endothelial Dysfunction: A Double‐Blind, Randomized, Placebo‐Controlled Crossover Trial

Abstract

Background: A family history of premature coronary artery disease (CAD) is a well-known risk factor for cardiovascular events. Hypothesis: Atorvastatin may improve endothelial dysfunction (ED) in the first-degree relatives (FDRs) of patients with premature CAD with ED. Methods: Thirty-five FDRs (median age, 52 years [interquartile range (IQR), 46-57 years], 21 male) of patients with premature CAD with ED were recruited in a prospective trial with a crossover double-blind design: 6 weeks of treatment with atorvastatin 40 mg/day followed by placebo, or vice versa. After each treatment, the digital pulse wave amplitude was determined by EndoPAT to obtain the reactive hyperemia index (RHI), a measure for endothelial function. The primary outcome was the difference of RHI between atorvastatin and placebo treatment.Results: Low-density lipoprotein cholesterol was lower after atorvastatin compared with placebo treatment (124 [102-145] mg/dL vs 67 [50-73] mg/dL, P < 0.001). However, RHI was not different after atorvastatin compared with placebo treatment (1.9 [1.5-2.4] vs 1.9 [1.6-2.2], P = 0.902). Also, the augmentation index was similar after each treatment. These results were observed both in subjects who had indications for statin treatment (31%) and those who did not (69%) according to National Cholesterol Education Program Adult Treatment Panel III guidelines. Conclusions: Despite improvement in the lipid profile, atorvastatin failed to improve ED in the FDRs of patients with premature CAD with ED. Although we identified those with ED in FDRs of patients with premature CAD as a high-risk group for future cardiovascular events, atorvastatin treatment may not be a beneficial primary prevention strategy for this population.

Response to Statin Therapy in Obstructive Sleep Apnea Syndrome: A Multicenter Randomized Controlled Trial

“…In this relatively healthy population of OSA patients, we did not confirm the beneficial effect on vascular compliance that we have previously reported with statins in rats exposed to intermittent hypoxia [ 22 ]. This result is in accordance with another human study showing that, despite improvement in the lipid profile, 6 weeks of atorvastatin treatment (40 mg/day) failed to improve endothelial dysfunction in the first-degree relatives of patients with premature coronary artery disease [ 36 ]. The atorvastatin dosage used here (40 mg/day) may have potentially been too low to improve endothelial function and atherosclerosis markers in OSA patients.…”

Reproducibility of peripheral arterial tonometry measurements in male cardiovascular patients

“…The clinical application of EndoPAT ® is of evaluative rather than discriminative nature, and although published studies have used this method to distinguish populations with differing cardiovascular risk profiles, it would be desirable to have a tool that can detect treatment effects. If the RHI is used to establish a treatment effect for an individual patient, then an improvement in RHI of at least 47% (LSC) would be necessary, an improvement that so far has not been achieved by any treatment studies .…”

All-cause mortality and cardiovascular events with nicorandil in patients with IHD: Systematic review and meta-analysis of the literature

“…The potential reasons of the different benefits of nicorandil in IHD patients with and without hemodialysis are not clear. It is well known that the ischemic injuries of the heart in hemodialysis patients with IHD might be induced not only by obstructive arteries but also by the increased inflammation [42,43], microvascular dysfunction [44,45], endothelial dysfunction [46][47][48][49], platelet dysfunction, thrombosis, and vasomotor dysfunction [50,51]. The biological functions of nicorandil of nitric oxide release and its antiinflammatory effects might partially explain its benefit effect in hemodialysis individuals.…”