Abstract and Introduction
Abstract
Objective: Several large-scale studies have shed light on the primary preventive efficacy of statins against atherosclerotic diseases in the course of treatment of dyslipidemia. However, this efficacy in the management of dyslipidemia in relatively low-risk patients, particularly in women, has not been clarified. Here, we investigated the efficacy of dyslipidemia treatment with a statin on three indices that are widely used to assess atherosclerosis in postmenopausal women: carotid intima-media thickness (CIMT), arterial stiffness index β of the common carotid artery (carotid stiffness β), and brachial artery pulse wave velocity (baPWV).
Methods: The study enrolled 51 postmenopausal women aged 55 years or older with dyslipidemia. The participants were randomly divided into two treatment groups and received a single daily administration of 2.5 mg of rosuvastatin or no statin therapy as control.
Results: At baseline, the groups did not significantly differ with regard to the three indices. At the third and 12th months of treatment, both carotid stiffness β and baPWV values were significantly lower than those of the control group. As for CIMT, the value was significantly lower in the statin group than in the control group at 12 months of treatment. These changes were in conjunction with a significant decrease in low-density lipoprotein cholesterol. Interestingly, changes in CIMT during the 12-month period were significantly correlated with changes in high-sensitivity C-reactive protein during the 3-month period independently of lipid profile.
Conclusions: The potent statin improves baPWV and carotid stiffness β, in addition to CIMT (surrogate markers of coronary artery disease), in postmenopausal women with low-risk dyslipidemia. Further studies to clarify the common mechanisms underlying the link between cholesterol-lowering therapy and atherosclerosis in post-menopausal women are required.
Introduction
Atherosclerosis is a leading cause of atherosclerotic diseases such as coronary artery diseases (CADs). Given the important role of dyslipidemia in the progression of these diseases, improvement in lipid profile represents an important risk reduction strategy. Statins, which inhibit 3-hydroxy-3-methylglutaryl coenzyme A reductase, are standard therapeutic treatments for patients with dyslipidemia. Several recent large-scale clinical trials have demonstrated that the treatment of dyslipidemia with statins plays a role in the secondary prevention of atherosclerotic diseases. With regard to the primary prevention of atherosclerotic diseases through management of dyslipidemia, the Kyushu Lipid Intervention Study demonstrated that pravastatin at 10 to 20 mg/day reduced atherosclerotic diseases in these patients. However, little is known about the effect of lipid-lowering therapy with statins on atherosclerosis in healthy postmenopausal women.
Because women have conventionally been considered to be at lower risk for atherosclerotic diseases during periods of menstrual activity, most large randomized controlled studies of lipid-lowering therapy carried out to date have predominantly involved men. Because of an increase in the levels of low-density lipoprotein cholesterol (LDL-C), however, the rate of CADs in postmenopausal women has sharply increased. Given the probable role of the reduced levels of circulating estrogen associated with menopause in raising both LDL-C levels and CAD incidence, the potential beneficial effect of LDL-C-lowering therapy on postmenopausal women merits investigation.
In addition to increased arterial wall thickness, as assessed by carotid intima-media thickness (CIMT), increased arterial stiffness is also considered as an independent predictor of CAD. Brachial artery pulse wave velocity (baPWV) is widely used in conjunction with CIMT to assess the functional element of atherosclerosis, whereas the arterial stiffness index β of the common carotid artery (carotid stiffness β) has also recently been defined as a new arterial stiffness marker.
Here, to clarify the potential of statins to improve baPWV and carotid stiffness β in addition to CIMT, we used these surrogate markers of CAD to investigate the efficacy of statin therapy in postmenopausal women with low-risk dyslipidemia.