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Statins are recognized as the principal and most effective class of drugs for reducing serum cholesterol levels and, therefore, significantly reducing cardiovascular events and mortality. Statins may have a wide range of beneficial biological effects in addition to lipid lowering, a phenomenon commonly termed a ‘pleiotropic effect’. However, the dose-dependency of these effects remains unclear. The present study evaluated whether atorvastatin, a potent statin, ameliorates the serum markers of pleiotropic effects, with a focus on dose-dependency. The pleiotropic effects of treatment with atorvastatin 5 mg/day and 10 mg/day for six months each in 15 patients with primary hypercholesterolemia were assessed in a prospective, randomized, open-label, crossover, single-centre study. Atorvastatin treatment dose-dependently decreased a serum marker of oxidative stress as well as the serum low-density lipoprotein cholesterol level. However, serum markers of inflammation and fibrinolysis decreased independently of dose. In conclusion, the dose-dependency of atorvastatin’s pleiotropic effects differs among individual biological effects.

Sympathetic nerve activity is augmented by calcium-channel blocker treatment as a result of decreased blood pressure. Dihydropyridine calcium-channel blockers are divided into three different types. The purpose of the present study was to investigate whether treatment effects on hemodynamics, cardiac autonomic nerve activity and plasma norepinephrine levels differ among amlodipine (L type), efonidipine (L + T type) and cilnidipine (L + N type). We enrolled 14 hypertensive patients (seven males, seven females, 70 ± 6 years old) undergoing a monotherapy of amlodipine, efonidipine or cilnidipine into this prospective, open-labeled, randomized, crossover study. At baseline and every 6 months of the treatment period, we repeated the evaluation of hemodynamics, spectral analysis of heart rate variability and plasma norepinephrine levels. Blood pressure and pulse rate were comparable among the three treatments. The low-frequency (LF)/high-frequency (HF) power ratio, an index of cardiac sympathovagal balance, was significantly lower with efonidipine and cilnidipine than with amlodipine, while the HF/total power ratio, an index of cardiac vagal activity, revealed the opposite results. There was no significant correlation between the LF/HF ratio and plasma norepinephrine levels. Antihypertensive monotherapy with efonidipine or cilnidipine attenuates cardiac sympathetic nerve activity more effectively than amlodipine monotherapy.