Bezafibrate Ameliorates Arterial Stiffness Assessed by Cardio-Ankle Vascular Index in Hypertriglyceridemic Patients with Type 2 Diabetes Mellitus

Yamaguchi, Takashi; Shirai, Kohji; Nagayama, Daiji; Nakamura, Shoko; Oka, Rena; Tanaka, Sho; Watanabe, Yasuhiro; Imamura, Hajime; Sato, Yuta; Kawana, Hidetoshi; Ohira, Masahiro; Saiki, Atsuhito; Shimizu, Naomi; Tatsuno, Ichiro

doi:10.5551/jat.45799

Cited by 15 publications

(10 citation statements)

References 47 publications

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“…This suggested that serial assessments of arterial stiffness using CAVI could serve as an indicator of the need for treatment. Moreover, several interventional studies showed that nonpharmacological and pharmacological treatments were associated with an improvement in CAVI 27 – 29 ) . To determine the utility of CAVI in patients with ACS, more clinical and experimental studies are required.…”

Section: Discussionmentioning

confidence: 99%

Impact of Cardio-Ankle Vascular Index on Long-Term Outcome in Patients with Acute Coronary Syndrome

Kirigaya

Iwahashi

Tahakashi

et al. 2020

JAT

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The purpose of this study is to investigate the impact of arterial stiffness assessed using Cardio-ankle Vascular Index (CAVI) on long-term outcome after acute coronary syndrome (ACS). Methods: A total of 387 consecutive patients (324 males; age, 64 11 years) with ACS were enrolled. We examined CAVI and brachial-ankle pulse wave velocity (ba PWV) as the parameters of arterial stiffness. The patients were divided into two groups according to the cutoff value of CAVI determined using the receiver operating characteristic curve for the prediction of major adverse cardiovascular events (MACE): low-CAVI group, 177 patients with CAVI 8.35; high-CAVI group, 210 patients with CAVI ≥ 8.35. The primary endpoint was the incidence of MACE (cardiovascular death, recurrence of ACS, heart failure requiring hospitalization, or stroke). Results: A total of 62 patients had MACE. Kaplan-Meier analysis demonstrated a significantly higher probability of MACE in the high-CAVI group than in the low-CAVI group (median follow-up: 62 months; log-rank, p 0.001). Multivariate analysis suggested that CAVI was an independent predictor of MACE (hazard ratio [HR], 1.496; p 0.02) and cardiovascular death (HR, 2.204; p 0.025), but ba PWV was not. We investigated the incremental predictive value of adding CAVI to the GRACE score (GRS), a validated scoring system for risk assessment in ACS. Stratified by CAVI and GRS, a significantly higher rate of MACE was seen in patients with both higher CAVI and higher GRS than the other groups (p 0.001). Furthermore, the addition of CAVI to GRS enhanced net reclassification improvement (NRI) and integrated discrimination improvement (IDI) (NRI, 0.337, p 0.034; and IDI, 0.028, p 0.004). Conclusion: CAVI was an independent long-term predictor of MACE, especially cardiovascular death, adding incremental clinical significance for risk stratification in patients with ACS. has attracted attention as a potentially useful parameter for risk stratification of patients with ACS 3, 4). Cardio-ankle vascular stiffness index (CAVI) is a noninvasive measure of arterial stiffness that is not influenced by blood pressure at the time of examination 5, 6). We previously reported that high CAVI was an independent predictor of cardiovascular (CV) events and nonfatal ischemic stroke in patients with ACS 3). However,

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Section: Discussionmentioning

confidence: 99%

Impact of Cardio-Ankle Vascular Index on Long-Term Outcome in Patients with Acute Coronary Syndrome

Kirigaya

Iwahashi

Tahakashi

et al. 2020

JAT

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“…Eicosapentaenoic acid decreases CAVI together with a reduction in oxidized LDL 71 ) . Yamaguchi et al 72 ) reported that bezafibrate ameliorates CAVI accompanied by improvement of remnant-like particle cholesterol and diacron-reactive oxygen metabolites. In patients with dyslipidemia, coexisting abnormal glycolipid metabolism and oxidative stress may affect CAVI.…”

Section: Various Factors Affecting Cavi (Cross-sectional Studies)mentioning

confidence: 99%

New Horizons of Arterial Stiffness Developed Using Cardio-Ankle Vascular Index (CAVI)

Saiki

Ohira

Yamaguchi

et al. 2020

JAT

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105

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Arterial stiffness is recognized mainly as an indicator of arteriosclerosis and a predictor of cardiovascular events. Cardio-ankle vascular index (CAVI), which reflects arterial stiffness from the origin of the aorta to the ankle, was developed in 2004. An important feature of this index is the independency from blood pressure at the time of measurement. A large volume of clinical evidence obtained using CAVI has been reported. CAVI is high in patients with various atherosclerotic diseases including coronary artery disease and chronic kidney disease. Most coronary risk factors increase CAVI and their improvement reduces CAVI. Many prospective studies have investigated the association between CAVI and future cardiovascular disease (CVD), and proposed CAVI of 9 as the optimal cutoff value for predicting CVD. Research also shows that CAVI reflects afterload and left ventricular diastolic dysfunction in patients with heart failure. Furthermore, relatively acute changes in CAVI are observed under various pathophysiological conditions including mental stress, septic shock and congestive heart failure, and in pharmacological studies. CAVI seems to reflect not only structural stiffness but also functional stiffness involved in acute vascular functions. In 2016, Spronck and colleagues proposed a variant index CAVI0, and claimed that CAVI0 was truly independent of blood pressure while CAVI was not. This argument was settled, and the independence of CAVI from blood pressure was reaffirmed. In this review, we summarize the recently accumulated evidence of CAVI, focusing on the proposed cutoff values for CVD events, and suggest the development of new horizons of vascular function index using CAVI. appropriate in studies that examine the effect of hypertension or the effect of antihypertensive drugs on intrinsic arterial stiffness. To overcome this problem, Hayashi 4) proposed the stiffness parameter , an index reflecting arterial stiffness of local arterial segment, which is not influenced by blood pressure at the time of measurement. Subsequently, this theory has been applied to a new arterial stiffness index called cardio-ankle vascular index (CAVI) developed in 2004 5) , and this index reflects the stiffness of the arterial tree from the origin of the aorta to the ankle. The CAVI equation was essentially derived from the stiffness parameter , and the changes of the artery caliber in the equation during the cardiac cycle were obtained Copyright©2020 Japan Atherosclerosis Society This article is distributed under the terms of the latest version of CC BY-NC-SA defined by the Creative Commons Attribution License.

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“…Plasma triglyceride levels have recently garnered considerable attention as a residual risk for cardiovascular events 17) . Clinical studies have demonstrated that treatment with fibrates reduces cardiovascular events associated with hypertriglyceridemia [18][19][20][21] . Yet there are several limitations concerning the use of fibrates 22) ; for example, their activity on PPAR is relatively weak, and their efficacy depends on the targeted population.…”

Section: Introductionmentioning

confidence: 99%

Pemafibrate, A Novel Selective Peroxisome Proliferator-Activated Receptor α Modulator, Reduces Plasma Eicosanoid Levels and Ameliorates Endothelial Dysfunction in Diabetic Mice

Suto

Fukuda

Shinohara

et al. 2021

JAT

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The official journal of the Japan Atherosclerosis Society and the Asian Pacific Society of Atherosclerosis and Vascular Diseases Original Article Aims: Various pathological processes related to diabetes cause endothelial dysfunction. Eicosanoids derived from arachidonic acid (AA) have roles in vascular regulation. Fibrates have recently been shown to attenuate vascular complications in diabetics. Here we examined the effects of pemafibrate, a selective peroxisome proliferator-activated receptor modulator, on plasma eicosanoid levels and endothelial function in diabetic mice.Methods: Diabetes was induced in 7-week-old male wild-type mice by a single injection of streptozotocin (150 mg/kg). Pemafibrate (0.3 mg/kg/day) was administered orally for 3 weeks. Untreated mice received vehicle. Circulating levels of eicosanoids and free fatty acids were measured using both gas and liquid chromatography-mass spectrometry. Endothelium-dependent and endothelium-independent vascular responses to acetylcholine and sodium nitroprusside, respectively, were analyzed.Results: Pemafibrate reduced both triglyceride and non-high-density lipoprotein -cholesterol levels (P 0.01), without affecting body weight. It also decreased circulating levels of AA (P 0.001), thromboxane B2 (P 0.001), prostaglandin E2, leukotriene B4 (P 0.05), and 5-hydroxyeicosatetraenoic acid (P 0.001), all of which were elevated by the induction of diabetes. In contrast, the plasma levels of 15-deoxy-12,14 -prostaglandin J2, which declined following diabetes induction, remained unaffected by pemafibrate treatment. In diabetic mice, pemafibrate decreased palmitic acid (PA) and stearic acid concentrations (P 0.05). Diabetes induction impaired endothelial function, whereas pemafibrate ameliorated it (P 0.001). The results of ex vivo experiments indicated that eicosanoids or PA impaired endothelial function. Conclusion:Pemafibrate diminished the levels of vasoconstrictive eicosanoids and free fatty acids accompanied by a reduction of triglyceride. These effects may be associated with the improvement of endothelial function by pemafibrate in diabetic mice.

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Bezafibrate Ameliorates Arterial Stiffness Assessed by Cardio-Ankle Vascular Index in Hypertriglyceridemic Patients with Type 2 Diabetes Mellitus

Cited by 15 publications

References 47 publications

Impact of Cardio-Ankle Vascular Index on Long-Term Outcome in Patients with Acute Coronary Syndrome

Impact of Cardio-Ankle Vascular Index on Long-Term Outcome in Patients with Acute Coronary Syndrome

New Horizons of Arterial Stiffness Developed Using Cardio-Ankle Vascular Index (CAVI)

Pemafibrate, A Novel Selective Peroxisome Proliferator-Activated Receptor α Modulator, Reduces Plasma Eicosanoid Levels and Ameliorates Endothelial Dysfunction in Diabetic Mice

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