Yoshihiro Araki

The influence of the obesity paradox and chronic kidney disease on long-term survival in a Japanese cohort with peripheral arterial disease

BACKGROUND This study analyzed risk factors for mortality in peripheral arterial disease (PAD), including body mass index (BMI) and estimated glomerular filtration rate (eGFR). Risk factors for long-term survival are unclear in patients with PAD. The origin of the obesity paradox, a paradoxical decrease in mortality with increasing BMI, is also uncertain in these patients. METHODS A prospective cohort study was performed in 652 patients (aged 71.3 +/- 9.4 years old) with PAD. RESULTS The 1-, 5-, 10- and 15-year survival rates were 94.5%, 70.4%, 45.2%, and 21.1%, respectively, in patients with intermittent claudication, and 72.7%, 27.2%, 11.6%, and 5.8%, respectively, in those with critical limb ischemia (CLI). In Cox multivariate analysis, a significant association with all-cause mortality was found for CLI (hazard ratio [HR], 1.931; 95% confidence interval [CI], 1.089-3.422; P = .024), diabetes (HR, 2.111; 95% CI, 1.247-3.572; P = .005), BMI (HR, 0.879; 95% CI, 0.804-0.962; P = .005), and eGFR (HR, 0.985; 95% CI, 0.971-0.998l; P = .028). These parameters were also significant risk factors for cardiovascular mortality. Fibrinogen (HR, 1.003; 95% CI, 1.001-1.005; P = .014) and cerebrovascular disease (HR, 1.730; 95% CI, 1.021-2.930; P = .045) were identified as risk factors for all-cause mortality. The adjusted HR for mortality of BMI <21.5 vs >or=21.5 kg/m(2) was 1.772 (95% CI, 1.378-2.279; P < .001). BMI had positive correlations with triglyceride and albumin concentrations and negative correlations with the fibrinogen level and chronic obstructive pulmonary disease (P = .005). CONCLUSIONS Low BMI, eGFR, CLI, and diabetes are significant risk factors for mortality in PAD. The obesity paradox was verified and may be partly explained by low BMI mediated by malnutrition and systemic inflammation due to PAD or chronic obstructive pulmonary disease.

High-sensitivity C-reactive Protein, Lipoprotein(a) and Homocysteine are Risk Factors for Coronary Artery Disease in Japanese Patients with Peripheral Arterial Disease

AIM The goal of the study was to investigate the relationships between coronary artery disease (CAD) and risk factors, including the serum levels of high-sensitivity C-reactive protein (hs-CRP), lipoprotein(a) (Lp(a)) and homocysteine, in Japanese patients with peripheral arterial disease (PAD). METHODS Coronary angiography was performed in 451 patients with PAD, among whom the prevalence and clinical characteristics of CAD were analyzed. A multiple logistic analysis was used to evaluate the relationships between CAD and the risk factors. The relationships between the severity of coronary arterial lesions and the risk factors were evaluated using multiple regression analysis. RESULTS The prevalence of CAD (≥70% luminal diameter narrowing or a history of CAD) and coronary artery stenosis (≥50%) was 55.9% and 74.1%, respectively, and the rate of CAD (≥70%) with single-, double- and triple-vessel disease was 25.9%, 13.5% and 10.6%, respectively. The prevalence of diabetes was higher among the patients with CAD than among those without. The serum levels of hs-CRP, Lp(a), and homocysteine were higher in the patients with CAD, whereas the estimated glomerular filtration rates and HDL-cholesterol levels were lower in these patients. According to the multiple logistic analysis, CAD was related to diabetes (hazard ratio [HR]: 2.253; 95% confidence interval [CI]: 1.137-4.464, p=0.020), hs-CRP (HR: 1.721; 95% CI: 1.030-2.875, p=0.038), Lp(a) (HR: 1.015; 95% CI: 1.001-1.029, p=0.041) and homocysteine (HR: 1.084; 95% CI: 1.012-1.162, p=0.021). Furthermore, diabetes and the D-dimer and LDL-cholesterol levels exhibited significant relationships with the number of stenotic coronary lesions in the stepwise multiple regression analysis (p＜0.05). CONCLUSIONS Diabetes, hs-CRP, Lp(a), homocysteine and lipid abnormalities are critical risk factors for CAD in Japanese patients with PAD.

Sex-related differences in Japanese patients with peripheral arterial disease.

OBJECTIVE The goal of the study was to examine possible sex-related differences in the clinical characteristics and risk factors in Japanese patients with peripheral arterial disease (PAD). METHODS Sex-related differences in clinical profiles, risk factors and treatments were examined in 730 consecutive patients with PAD (148 women (20.3%) and 582 men (79.7%)). RESULTS The mean age of the women was higher than that of the men (73.6 ± 11.2 vs. 70.9 ± 9.1 years old, p = 0.002) and the proportion of subjects aged ≥ 75 years old was also higher in women (P=0.005). Women more frequently had critical limb ischemia (P < 0.001) and diabetes mellitus (P = 0.026), but less frequent smoking and alcohol intake, compared to men (P< 0.001). Total cholesterol (P < 0.001) and LDL cholesterol (P = 0.014) were higher in women. Fontaine stages were correlated with age, diabetes, cerebral infarction and women (p < 0.001). The prevalence of iliac artery lesions was higher in men (p< 0.001), whereas that for below the knee lesions was higher in women (p < 0.001). The number of affected below the knee arteries was also higher in women than in men (p < 0.001). The prevalence of medical treatment was higher in women (P = 0.009) and major amputation tended to be higher in women (p = 0.056). CONCLUSIONS Women had more severe symptomatic states and uncontrolled risk factors. The prevalence of iliac artery lesions was lower, but below the knee lesions were more severe in women.

Prevalence and risk factors for renal artery stenosis and chronic kidney disease in Japanese patients with peripheral arterial disease

The prevalence and risk factors for renal artery stenosis (RAS) and chronic kidney disease (CKD) are unclear in Japanese patients with peripheral arterial disease (PAD). To examine these issues, we performed renal angiography in 410 patients with PAD. Renal function and damage were assessed using the estimated glomerular filtration rate (eGFR) and urinary level of microalbumin (MA). Multiple logistic and multiple regression analyses were used to examine the relationships of potential risk factors with RAS and CKD. In all, 94 subjects (22.9%) had RAS >50% and 45 subjects (11.0%) had RAS >75%. The incidences of an abnormal level of MA and renal insufficiency (eGFR <60 ml min–1 per 1.73 m2) were 37.0 and 60.7%, respectively. RAS ⩾50% was associated with critical limb ischemia (CLI; hazard ratio (HR) 2.519; 95% confidence interval (CI) 1.203–5.276, P=0.014), coronary heart disease (CHD; HR 2.143; 95% CI 1.129–4.069; P=0.020) and hypertension (HR 1.907; 95% CI 1.009–3.628; P=0.045). RAS ⩾75% had a relationship with hypertension (HR 3.093; 95% CI 1.002–9.548; P=0.048). eGFR was negatively correlated with age, uric acid and CHD (P=0.013), and MA had a significant positive correlation with low-density lipoprotein cholesterol, CLI, age, CHD and diabetes (P<0.001). These results show that the prevalences of RAS and CKD are very high in Japanese patients with PAD; that CLI and CHD are major risk factors for RAS; and that hyperuricemia, hypercholesterolemia and diabetes are risk factors for CKD in PAD. We also found that MA is a simple and noninvasive marker of renal dysfunction and general vascular damage.

15-Year Patency and Life Expectancy After Primary Stenting Guided by Intravascular Ultrasound for Iliac Artery Lesions in Peripheral Arterial Disease.

OBJECTIVES The purpose of this study was to evaluate 15-year patency and life expectancy after endovascular treatment (EVT) with primary stenting guided by intravascular ultrasound (IVUS) for iliac artery lesions. BACKGROUND Fifteen-year patency, factors causing restenosis, and survival after IVUS-guided EVT are unclear based on the TransAtlantic Inter-Society Consensus II (TASC-II) classification in peripheral arterial disease (PAD). METHODS EVT was performed for 507 lesions in 455 patients with PAD. The 15-year endpoints were primary, primary-assisted, and secondary patency; overall survival; freedom from major adverse cardiovascular events (MACE); and freedom from major adverse cardiovascular and limb events (MACLE). RESULTS The 5-, 10-, and 15-year primary and secondary patencies were 89%, 83%, and 75%, respectively, and 92%, 91%, and 91%, respectively. There were no significant differences among TASC-II categories. CONCLUSIONS IVUS-guided stenting for the iliac artery had favorable 15-year patency in all TASC categories. Life expectancy after EVT was poor, but stenting is feasible for patients with PAD.

Intravascular Ultrasound Analysis of Correlation between Plaque-Morphology and Risk Factors in Peripheral Arterial Disease

OBJECTIVE To analyze relationships between plaque-morphology classified by intravascular ultrasound (IVUS) and risk factors in patients with peripheral arterial disease (PAD). METHODS We performed IVUS in 203 patients with PAD. Multiple regression and logistic analysis were used to assess relationships between plaque-morphology (degree of calcification, presence of a lipid core, intimal flap and thrombus) and risk factors including diabetes mellitus, hypertension, dyslipidemia, estimated glomerular filtration rate (eGFR), HbA1c and the homeostasis model assessment-insulin resistance ratio (HOMA-IR). RESULTS IVUS data led to 22% of lesions being classified as soft, 18% as fibrous, 32% as calcified, and 28% as mixed. Calcification was present in the superficial and deep layers in 65% and 35% of cases, respectively, and a lipid core, intimal flap and thrombus were found in 31%, 5.4% and 3.0%, respectively. The calcified angle correlated with HbA1c and eGFR (p < 0.05). Associations were found between deep calcification and HOMA-IR (odds ratio: 4.4, p < 0.05) and a lipid core and hypercholesterolemia (odds ratio: 3.2, p < 0.05). The odds ratio for intimal flap was 15.6 times with hypercholesterolemia (p < 0.05) and 16.9 times with a high HOMA-IR (p < 0.01). CONCLUSION Plaque calcification and morphology are associated with chronic kidney disease, insulin resistance and dyslipidemia in PAD patients.

Effects of Antiplatelet Agents and Other Factors on Neointimal Proliferation in Iliac Artery Stenting: Intravascular Ultrasound Analysis

OBJECTIVE To use intravascular ultrasound to investigate the effects of antiplatelet agents and other factors on neointimal proliferation after stent implantation for iliac artery stenosis. PATIENTS AND METHODS The subjects were 109 patients with peripheral arterial disease who underwent stent implantation in the iliac artery. Intravascular ultrasound was performed to evaluate lesion area, stent dilatation and neointimal proliferation before, just after, and six months after stenting. Multiple regression analysis was performed to examine the relationship of the neointimal proliferation rate with antiplatelet agents and other factors. RESULTS At the time of stent implantation, a Palmaz stent resulted in a significant increase in lumen area compared with a Wallstent (p < 0.05). Six months later, self-expanding Wallstent and Luminexx stents showed a significant increase in the stent-lumen area (p < 0.05). The neointimal proliferation rate showed a significant negative correlation with beraprost and cilostazol (p < 0.05) and a significant positive correlation with serum creatinine (p < 0.01). There was no significant difference in the vessel lumen area including the proliferated intima among the three stents. CONCLUSION Suppression of neointimal proliferation can be achieved with beraprost or cilostazol whereas renal dysfunction may increase neointimal proliferation following stent implantation in iliac artery lesions.