Sarpogrelate Hydrochloride Decreases Cardio-Ankle Vascular Index Accompanied by Increased Serum Lipoprotein Lipase Mass in Type 2 Diabetic Patients

Abstract

SummaryThe 5-hydroxytryptamine2A receptor antagonist sarpogrelate hydrochloride exerts its effect not only by inhibition of platelet aggregation, but also by some pleiotropic effects. We have reported that a low serum lipoprotein lipase (LPL) mass level reflects insulin resistance and may be a risk factor for atherosclerotic diseases. The aim of this prospective study was to clarify the effect of sarpogrelate on serum LPL mass and cardio-ankle vascular index (CAVI) as a marker related to arterial stiffness.Thirty-five type 2 diabetic patients (21 males and 14 females) with ankle brachial indices higher than 0.90 received sarpogrelate hydrochloride 300 mg/day for 6 months. Serum LPL mass and CAVI were measured during the study.After 6 months of sarpogrelate hydrochloride treatment, CAVI decreased significantly (10.11 ± 0.92 to 9.87 ± 0.97, P < 0.05) and serum LPL mass increased significantly (58.2 ± 17.5 to 63.5 ± 21.4, P < 0.05). A negative correlation between change in CAVI and change in serum LPL mass was observed (r = -0.34, P < 0.05). Multiple regression analysis identified a change in serum LPL mass as a significant independent predictor for change in CAVI.We demonstrated that sarpogrelate hydrochloride decreased CAVI accompanied by increased serum LPL mass in type 2 diabetic patients. This result suggests that sarpogrelate hydrochloride improves arterial stiffness and is a potential treatment for diabetic angiopathy. (Int Heart J 2014; 55: 337-341) Key words: Diabetic angiopathy 5 -Hydroxytryptamine (5-HT) is closely related to the pathogenesis of diabetic angiopathy. Sarpogrelate hydrochloride (sarpogrelate), a selective 5-HT2A receptor antagonist, is used in diabetic patients with chronic arterial occlusive diseases.1) Sarpogrelate suppresses platelet aggregation, vascular endothelial dysfunction, and smooth muscle contraction mediated by 5-HT2A receptors.2,3) Furthermore, the effect of sarpogrelate on modification of adipocyte structure and function has been reported. 4)Recently, cardio-ankle vascular index (CAVI) has been developed as a marker related to arterial stiffness in Japan, which essentially reflects the stiffness of the aorta, femoral artery, and tibial artery. The CAVI is independent of blood pressure (BP) and has adequate reproducibility for clinical use. 5)Furthermore, no special technique is required for the measurement of CAVI. Several reports have demonstrated the usefulness of CAVI for the detection of atherosclerotic diseases. [5][6][7][8][9] However, the effect of sarpogrelate on CAVI is not clear.In this study, we investigated prospectively the effect of sarpogrelate on arterial stiffness assessed by CAVI in type 2 diabetic patients. Furthermore, factors contributing to the change in arterial stiffness were also analyzed.

Arterial Stiffness Is Significantly Associated With Left Ventricular Diastolic Dysfunction in Patients With Cardiovascular Disease

“…There have been several reports on possible effective pharmacologic therapies, such as ACE-I/ARB, CCB, statins, and sarpogrelate hydrochloride, and non-pharmacologic therapies, such as exercise and continuous positive airway pressure. [30][31][32][33][34][35][36][37][38][39] Further studies are needed to establish indicators and therapeutic methods for arterial stiffness.…”

Increased plasma serotonin metabolite 5-hydroxyindole acetic acid concentrations are associated with impaired systolic and late diastolic forward flows during cardiac cycle and elevated resistive index at popliteal artery and renal insufficiency in type 2 diabetic patients with microalbuminuria

“…5-HT2A receptor antagonist serves as a potent therapeutic agent for serotonin-induced micro-and macrovascular complications in diabetic patients. Treatment with 5-HT2A receptor antagonist improves endothelial function in patients with peripheral arterial disease [33] and also ameliorates arterial stiffness as assessed by cardioankle vascular index (CAVI) in diabetic patients [34]. Urinary 5-HIAA levels are higher in diabetic patients than in nondiabetic patients and administration of 5-HT2A receptor antagonist reduces UAE in diabetic patients with microalbuminuria [35].…”

Cardio-Ankle Vascular Index is Independently Associated with Future Cardiovascular Events in Outpatients with Metabolic Disorders

“…Furthermore, the present study suggests that CAVI can predict vascular events that may occur in the future. Moreover, CAVI has been shown to decrease following various interventions for coronary risks, including some medications for metabolic disorders, weight reduction, and smoking cessation 13,[28][29][30][31][32][33] . Therefore, CAVI is considered a good physiological surrogate marker for lifestyle changes such as smoking cessation and control of blood pressure and glucose level, which may be expected to contribute to the prevention of CVD.…”