Diet is one of the most important factors affecting healthy life expectancy through the onset of cardiovascular disease (CVD) risk as well as various chronic diseases. Because dietary habits and disease structure differ depending on the country, region, and/or race, evidence from each population is required. NIPPON DATA80/90 is a long-term cohort study of a representative Japanese population that participated in national nutrition surveys. Among the many findings of this cohort study, a dietary pattern with higher intake of fruits, vegetables, fish (n-3 polyunsaturated fatty acids), and dietary fiber and lower intake of salt as well as sodium-to-potassium ratio was found to be associated with a lower risk of CVD mortality. The results from our cohort study would be useful for effectively preventing CVD. This article reviews the published studies from the NIPPON DATA80/90 to highlight the significant findings that may be used to develop risk prevention strategies for CVD.

Aim: To examine the efficacy and safety of prasugrel vs clopidogrel in thrombotic stroke patients at risk of ischemic stroke.

Methods: This multicenter, active-controlled, randomized, double-blind, double-dummy, parallel group study enrolled thrombotic stroke patients aged ≥ 50 years at risk of ischemic stroke. Patients received prasugrel (3.75 mg/day) or clopidogrel (75 or 50 mg/day) for 24–48 weeks; other antiplatelet drugs were prohibited. The primary efficacy endpoint was the composite incidence of ischemic stroke, myocardial infarction (MI), and death from other vascular causes from the start to 1 day after treatment completion or discontinuation. Secondary efficacy endpoints included the incidences of ischemic stroke, MI, death from other vascular causes, ischemic stroke and transient ischemic attack, and stroke. Safety endpoints included bleeding events and adverse events (AEs).

Results: In the prasugrel (N=118) and clopidogrel (N=112; all received 75 mg) groups, the primary efficacy endpoint composite incidence (95% confidence interval) was 6.8% (3.0%–12.9%) and 7.1% (3.1%–13.6%), respectively. The risk ratio (prasugrel/clopidogrel) was 0.949 (0.369–2.443). Secondary efficacy endpoints followed a similar trend. The combined incidences of life-threatening, major, and clinically relevant bleeding were 5.0% and 3.5% in the prasugrel and clopidogrel groups, respectively. The incidences of all bleeding events and AEs were 19.2% and 24.6% and 76.7% and 82.5% in the prasugrel and clopidogrel groups, respectively. No serious AEs were causally related to prasugrel.

Conclusions: We observed a risk reduction of 5% with prasugrel vs clopidogrel, indicating comparable efficacy. There were no major safety issues for prasugrel.

Aims: Epidemiological evidence is extremely limited about high-sensitivity cardiac troponin T (hs-cTnT) and future coronary heart disease (CHD) events for the general population in countries with low mortality from CHD. Therefore, we investigated the association between hs-cTnT levels and the risk of incident CHD using a nested case–control study in a large Japanese cohort study.

Methods: The participants were residents of four Japanese communities in the Circulatory Risk in Communities Study (CIRCS). We obtained 120 cases (81 men and 39 women, aged 38–86 years at baseline) of first incident CHD and 240 controls matched by age, sex, communities, and blood sampling term. Serum hs-cTnT levels were measured using an electrochemiluminescence immunoassay with stored sera collected between 2001 and 2011. The median period between sampling at survey and CHD incidence was 2.0 (interquartile range, 0.9–3.7) years. After adjusting for conventional risk factors, the multivariable odds ratios (ORs) of CHD were calculated using conditional logistic regression analyses.

Results: hs-cTnT ranged from ≤ 3 (assay detection limit) to 155 ng/L. Compared with the lowest quartile of hs-cTnT, multivariable ORs (95% confidence intervals) of CHD for the second, third, and highest quartiles were 1.30 (0.57–2.95), 2.48 (1.09–5.64), and 3.01 (1.27–7.12), respectively. Similar associations were observed after adjusting for estimated glomerular filtration, or after excluding matched groups, including people with chronic kidney disease.

Conclusion: Serum hs-cTnT could predict CHD in the Japanese general population. These findings implicate a benefit from monitoring hs-cTnT to predict CHD even among populations in countries with low mortality from CHD.

Aim: In this study, we aimed to evaluate the association between age at menarche and risk of cardiovascular disease mortality.

Methods: In total, 54,937 women aged 40–79 years old between 1988 and 1990 without a history of cardiovascular disease were eligible for analysis and were followed through December 2009. We used the Cox proportional hazards models to examine the association between age at menarche and risk of cardiovascular disease.

Results: Compared with women with age at menarche of 15 years, the hazard ratios (95% confidence intervals) of stroke were 1.22 (0.85–1.75) for women with age at menarche of 9–12 years, 1.08 (0.85–1.36) for those of 13 years, 1.23 (1.02–1.47) for those of 14 years, 1.27 (1.07–1.50) for those of 16 years, 1.16 (0.95–1.41) for those of 17 years, and 1.39(1.16–1.68) for those of 18–20 years (P for trend=0.045). A similar pattern was observed for hemorrhagic stroke, ischemic stroke, and total cardiovascular disease. No such association was found for coronary heart disease. When stratified by age, for women aged 40–59 at baseline, the similar U-shaped association was observed. In contrast, for women aged 60–79 years at baseline, a significantly high hazard ratio was noted in the group of late age at menarche, but not in the group of early age at menarche.

Conclusions: Both women with early and late age at menarche were determined to have higher risk of death from stroke and cardiovascular disease.

Aim: Although many epidemiological studies have shown that obesity assessed by body mass index is associated with carotid intima-media thickness (cIMT), few studies have evaluated fat-free mass, which is a component of body composition. We investigated the associations between the combined fat mass index (FMI) and fat-free mass index (FFMI) with cIMT.

Methods: We conducted a cross-sectional study of 3,873 men and 9,112 women aged 20 years or older who lived in Miyagi prefecture, Japan. The FMI and FFMI were calculated as fat mass and fat-free mass divided by height squared, respectively. The indices were classified into sex-specific quartiles and were combined into 16 groups. The maximum common carotid artery was measured using high-resolution B-mode ultrasound. An analysis of covariance was used to assess associations between the combined FMI and FFMI with cIMT adjusted for age and smoking status. The linear trend test was conducted by stratifying the FMI and FFMI, scoring the categories from 1 (lowest) to 4 (highest), and entering the number as a continuous term in the regression model.

Results: In multivariable models, a higher FMI was not related to higher cIMT in men and women in most FFMI subgroups. Conversely, a higher FFMI was related to higher cIMT in all FMI subgroups (p＜0.001 for linear trend).

Conclusions: FMI was not associated with cIMT in most FFMI subgroups. Conversely, FFMI was positively associated with cIMT independently of FMI.

Aim: Lipoprotein(a) (Lp(a)) is a low-density lipoprotein-like particle containing apolipoprotein(a) (apo(a)) that increases the risk of atherosclerotic cardiovascular disease (ASCVD) in familial hypercholesterolemia (FH). Postprandial redistribution of apo(a) protein from Lp(a) to triglyceride-rich lipoproteins (TRLs) may also increase the atherogenicity of TRL particles. Omega-3 fatty acid (ω3FA) supplementation improves postprandial TRL metabolism in FH subjects. However, its effect on postprandial apo(a) metabolism has yet to be investigated.

Methods: We carried out an 8-week open-label, randomized, crossover trial to test the effect of ω3FA supplementation (4 g/day) on postprandial apo(a) responses in FH patients following ingestion of an oral fat load. Postprandial plasma total and TRL-apo(a) concentrations were measured by liquid chromatography with tandem mass spectrometry, and the corresponding areas under the curve (AUCs) (0–10h) were determined using the trapezium rule.

Results: Compared with no ω3FA treatment, ω3FA supplementation significantly lowered the concentrations of postprandial TRL-apo(a) at 0.5 (−17.9%), 1 (−18.7%), 2 (−32.6%), and 3 h (−19.2%) (P＜0.05 for all). Postprandial TRL-apo(a) AUC was significantly reduced with ω3FA by 14.8% (P＜0.05). By contrast, ω3FA had no significant effect on the total AUCs of apo(a), apoC-III, and apoE (P＞0.05 for all). The decrease in postprandial TRL-apo(a) AUC was significantly associated with changes in the AUC of triglycerides (r=0.600; P＜0.01) and apoB-48 (r=0.616; P＜0.01).

Conclusions: Supplementation with ω3FA reduces postprandial TRL-apo(a) response to a fat meal in FH patients; this novel metabolic effect of ω3FA may have implications on decreasing the risk of ASCVD in patients with FH, especially in those with elevated plasma triglyceride and Lp(a) concentrations. However, the clinical implications of these metabolic findings require further evaluation in outcome or surrogate endpoint trials.

Aim: This study aimed to report injury precipitating tissue loss and to provide updated information on the time from tissue loss occurrence to referral to a vascular center for patients who developed chronic limb-threatening ischemia (CLTI) in Japan.

Methods: We examined 450 patients who developed CLTI with tissue loss and were registered in a multicenter prospective study between October 2017 and June 2020. They were referred to the participating vascular centers for revascularization. Information on the injury precipitating tissue loss and time to referral was collected at registration. The severity of tissue loss was evaluated using the Wound, Ischemia, and foot Infection classification.

Results: Injury precipitating tissue loss was absent in 52.0% (95% confidence interval, 47.3%–56.6%) of the patients. The absence was associated with lower albumin levels and preserved pressure sensation. Although the time to referral was significantly shorter in cases without a history of prereferral revascularization, 16.8% (12.8%–20.7%) of the patients were referred to the vascular centers more than 3 months after tissue loss occurrence. Time to referral, but not the lack of a clear precipitant for tissue loss, was significantly associated with the severity of tissue loss.

Conclusion: A clear precipitant for tissue loss was often lacking, particularly in patients with low albumin levels and preserved pressure sensation. Delayed referral to a vascular center is still common.

Aims: The Academic Research Consortium (ARC) has proposed international criteria to standardize the definition of high bleeding risk (HBR) in patients undergoing percutaneous coronary intervention (PCI). In this context, Japan has also established its own guidelines, that is, the Japanese version of HBR (J-HBR) criteria. However, the J-HBR criteria have not been fully validated, especially in patients with acute myocardial infarction (MI).

Methods: This bi-center registry included 1079 patients with acute MI undergoing primary PCI in a contemporary setting. Patient bleeding risks were evaluated using the ARC-HBR and J-HBR criteria. The primary endpoint was rates of major bleeding events (Bleeding Academic Research Consortium type 3 or 5) at 1 year.

Results: Of the 1079 patients, 505 (46.8%) and 563 (52.2%) met the ARC-HBR and J-HBR criteria, respectively. Patients who met the J-HBR criteria were found to have a higher rate of major bleeding events at 1 year than those who did not (12.8% vs. 3.3%, p＜0.001). When patients were scored and stratified using the J-HBR major and minor criteria, risks of major bleedings were progressively increased with the increase in the number of J-HBR criteria. In the receiver operating characteristic curve analysis, the ARC-HBR and J-HBR significantly predicted subsequent major bleedings after PCI, with ARC-HBR having greater predictive ability than J-HBR.

Conclusions: More than half of the patients with acute MI undergoing primary PCI in Japan met the J-HBR criteria. Although the J-HBR criteria successfully identified patients who were likely to develop major bleeding events after primary PCI, the superiority of J-HBR to ARC-HBR in predicting bleeding outcomes warrants further investigation.