Age-related difference of the association of cardiovascular risk factors with the cardio-ankle vascular index in the Cardiovascular Prognostic Coupling Study in Japan (the Coupling Registry).

The value of the cardio-ankle vascular index (CAVI) increases with age. All large-scale studies of the CAVI have investigated patients <80 years old. Thus, the clinical characteristics of high CAVI in patients aged 80 or more remain unclear. Therefore, we investigated (1) the CAVI in very elderly patients and (2) the determinants of a high CAVI in high-risk patients, including very elderly patients. The Cardiovascular Prognostic Coupling Study in Japan (Coupling Registry) is a prospective observational study of Japanese outpatients with any cardiovascular risk factors. We enrolled 5109 patients from 30 institutions (average age 68.7 ± 11.4 years, 52.4% males). We investigated the determinants of the CAVI by separating the patients into three groups: 970 middle-aged (<60 years), 3252 elderly (60-79 years), and 887 very elderly (≥80 years) patients. The CAVI values of the males were significantly higher those of the females in all age groups (<60 years: 7.81 ± 1.11 vs. 7.38 ± 0.99, P < .001; 60-79 years: 9.20 ± 1.29 vs. 8.66 ± 1.07, P < .001; ≥80 years: 10.26 ± 1.39 vs. 9.51 ± 1.12, P < .001). In all age groups, the CAVI of the patients with diabetes/glucose tolerance disorder was higher than that of the patients without diabetes/glucose tolerance disorder (<60 years: 7.82 ± 1.22 vs 7.58 ± 1.03, P = .002; 60-79 years: 9.23 ± 1.20 vs 8.78 ± 1.19, P < .001; ≥80 years: 10.04 ± 1.24 vs 9.75 ± 1.32, P = .002). The determinants of the CAVI in these very elderly patients were age, male sex, low BMI, and mean blood pressure. Diabetes/glucose tolerance disorder and glucose were independently associated with the CAVI in the patients aged <60 years and 60-79 years, but not in those aged ≥80 years after adjusting for other covariates.

Rationale, design, and baseline characteristics of the Cardiovascular Prognostic COUPLING Study in Japan (the COUPLING Registry).

Vascular biomarkers, including the cardio-ankle vascular index (CAVI), are increasingly being recognized as important indicators of cardiovascular risk. CAVI has been shown to have good discriminative ability for detecting new-onset hypertension, but results of studies investigating cardiovascular risk prediction are inconsistent. Furthermore, there is a lack of data on the prognostic value of changes in CAVI over time. The Cardiovascular Prognostic Coupling study was designed to determine the impact of baseline CAVI and changes in CAVI on cardiovascular events in a Japanese cohort. The design of the ongoing, multicenter, prospective, observational registry and baseline characteristics of the enrolled population are reported. Eligible consecutive patients were aged ≥30 years, had ≥1 cardiovascular risk factor, and were being treated according to relevant Japanese guidelines. The primary outcome is time to onset of a major cardiovascular event (a composite of cerebral infarction, cerebral hemorrhage, subarachnoid hemorrhage, stroke of unknown etiology, myocardial infarction, cardiovascular intervention for angina pectoris, and sudden death). Screening and enrollment occurred over a period of 3 years, followed by ≥7 years of follow-up, with CAVI determined annually. A total of 5279 patients were registered, of whom 5109 had baseline data available and will be included in future analyses. Mean CAVI at baseline was 8.8 ± 1.4. The proportion of patients with CAVI of <8, 8-10 or >10 was 25.3%, 57.0%, and 17.7%, respectively. Data from this registry should provide information on the significance of baseline CAVI and change in CAVI as indicators of cardiovascular prognosis in a representative patient population.

Comparison of clinical outcomes following percutaneous coronary intervention versus optimal medical therapy based on gray-zone fractional flow reserve in stable angina patients with intermediate coronary artery stenosis (COMFORTABLE prospective study): Study protocol for a multicenter randomized controlled trial.

BACKGROUND: Even in the current drug-eluting stent era, revascularization for coronary stenosis with fractional flow reserve (FFR) between 0.75 and 0.80, the so-called "gray zone," is a matter of debate. Previous studies have reported conflicting results regarding outcomes of revascularization versus deferral for coronary stenosis when FFR values are in the gray zone, but these studies have had differing designs and populations. We therefore will investigate whether medical therapy plus percutaneous coronary intervention (PCI) is superior to medical therapy alone in reducing major cardiovascular events in patients presenting with coronary stenosis with gray zone FFR values. METHODS/DESIGN: This is a prospective, multicenter, open-label, parallel group, randomized, controlled, superiority study. A total of 410 eligible participants will be recruited and randomized to either the medical therapy plus PCI group or the medical therapy alone group. The primary endpoint is 1-year major adverse cardiac events (MACEs), defined as a combined endpoint of all-cause death, nonfatal myocardial infarction (MI), or unplanned target vessel revascularization (TVR). Secondary endpoints include MACE at 2 and 5 years. Moreover, each individual component of the primary endpoint, cardiovascular death, target vessel-related and non-target vessel-related MI, all MI, clinically driven TVR or non-TVR, all revascularization, stent thrombosis, and angina symptom status will be evaluated at 1, 2, and 5 years. DISCUSSION: This is the first prospective, multicenter, randomized, controlled study to investigate the superiority of medical therapy plus PCI over medical therapy by itself in reducing major cardiovascular events in patients presenting with coronary stenosis with "gray zone" FFR values. The results will help interventional cardiologists in making revascularization decisions regarding coronary stenosis with gray zone FFR values. TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trials Registry, UMIN000031526 . Registered on 1 March 2018.

Metabolic syndrome is strongly associated with chronic subclinical inflammation in patients achieving optimal low-density lipoprotein-cholesterol levels in secondary prevention of cardiovascular disease.

BACKGROUND: The dual goals of low-density lipoprotein-cholesterol (LDL-C) and C-reactive protein (CRP) reduction are important for secondary prevention of cardiovascular disease. However, the relevant factors of subclinical inflammation in patients with optimal LDL-C were not clearly demonstrated. This study sought to test the hypothesis that the metabolic syndrome (MetS) is associated with subclinical inflammation in patients achieving optimal LDL-C. METHODS AND RESULTS: A total of 227 Japanese subjects with a prior history of ischemic heart disease and optimal LDL-C (LDL-C <100 mg/dl) were enrolled. When compared with patients with low CRP (<0.1 mg/dl), those with a high CRP (> or =0.1 mg/dl) had a significantly higher prevalence of visceral obesity, elevated triglyceride, lower high-density lipoprotein-cholesterol (HDL-C), hypertension, impaired fasting glucose, and a higher prevalence of MetS. A linear relationship between an increase in number of MetS components and CRP was observed (trend, p<0.001). In multivariate logistic analysis, visceral obesity (odds ratio 6.54; 95% confidence interval 2.99-14.3), low HDL-C (2.78; 1.09-7.12) and impaired fasting glucose (6.72; 3.30-13.7), and MetS (10.4; 5.18-20.7) were associated with higher CRP. CONCLUSIONS: MetS is well associated with higher CRP concentrations in patients who achieved optimal LDL-C levels.