Aims: This study aims to investigate the association between serum small dense low-density lipoprotein (sdLDL) cholesterol level and the development of coronary heart disease (CHD) in a Japanese ...community. Methods: A total of 3,080 participants without prior cardiovascular disease, aged 40 years or older, were followed up for 8 years. The participants were divided into the quartiles of serum sdLDL cholesterol levels. The risk estimates were computed using a Cox proportional hazards model. Results: During the follow-up period, 79 subjects developed CHD. Subjects in the highest quartile had a 5.41- fold (95% confidence interval, 2.12–13.82) higher risk of CHD than those in the lowest quartile after controlling for confounders. In the analysis classifying the participants into four groups according to the levels of serum sdLDL cholesterol and serum low-density lipoprotein (LDL) cholesterol levels, the risk of CHD almost doubled in subjects with sdLDL cholesterol of ≥ 32.9 mg/dL (median), regardless of serum LDL cholesterol levels, as compared with subjects with serum sdLDL cholesterol of ＜32.9 mg/dL and serum LDL cholesterol of ＜120.1 mg/dL (median). When serum sdLDL cholesterol levels were incorporated into a model with known cardiovascular risk factors, c-statistics was significantly increased (from 0.77 to 0.79; p=0.02), and the net reclassification improvement was also significant (0.40; p＜0.001). Conclusions: The present findings suggest that the serum sdLDL cholesterol level is a relevant biomarker for the future development of CHD that offers benefit beyond the serum LDL cholesterol level and a possible therapeutic target to reduce the burden of CHD in a Japanese community.
Aim:To develop and validate a new risk prediction model for predicting the 10-year risk of atherosclerotic cardiovascular disease (ASCVD) in Japanese adults. Methods: A total of 2,454 participants ...aged 40–84 years without a history of cardiovascular disease (CVD) were prospectively followed up for 24 years. An incident ASCVD event was defined as the first occurrence of coronary heart disease or atherothrombotic brain infarction. A Cox proportional hazards regression model was used to construct the prediction model. In addition, a simplified scoring system was translated from the developed prediction model. The model performance was evaluated using Harrell’s C statistics, a calibration plot with the Greenwood-Nam-D’Agostino test, and a bootstrap validation procedure. Results: During a median of a 24-year follow-up, 270 participants experienced the first ASCVD event. The predictors of the ASCVD events in the multivariable Cox model included age, sex, systolic blood pressure, diabetes, serum high-density lipoprotein cholesterol, serum low-density lipoprotein cholesterol, proteinuria, smoking habits, and regular exercise. The developed models exhibited good discrimination with negligible evidence of overfitting (Harrell’s C statistics: 0.786 for the multivariable model and 0.789 for the simplified score) and good calibrations (the Greenwood-Nam-D’Agostino test: P=0.29 for the multivariable model, 0.52 for the simplified score). Conclusion: We constructed a risk prediction model for the development of ASCVD in Japanese adults. This prediction model exhibits great potential as a tool for predicting the risk of ASCVD in clinical practice by enabling the identification of specific risk factors for ASCVD in individual patients.
Background: The prevalence of sarcopenia defined using the Asian Working Group for Sarcopenia (AWGS) criteria in Asian communities has not been fully addressed. Moreover, few studies have addressed ...the influence of sarcopenia on mortality. Methods: A total of 1,371 and 1,597 residents aged 65 years or older participated in health surveys in 2012 and 2017. Sarcopenia was determined using the AWGS definition. Factors associated with the presence of sarcopenia were assessed using a logistic regression model in participants in the 2012 survey. Subjects in the 2012 survey were followed-up prospectively for a median of 4.3 years. Mortality risk for subjects with sarcopenia was examined using the Cox proportional hazards model. Results: The crude prevalence of sarcopenia was 7.4% and 6.6% in participants at the 2012 and 2017 surveys, respectively; there was no significant difference between surveys (P = 0.44). The prevalence of sarcopenia increased significantly with age in both sexes (both P for trend <0.001). Subjects with sarcopenia were more likely to exercise less regularly, to intake less total energy, and to exhibit a disability in activity of daily living than those without. The multivariable-adjusted hazard ratio for all-cause mortality was 2.20 (95% confidence interval, 1.25–3.85) in subjects with sarcopenia, compared to those without. Conclusions: Approximately 7% of older subjects had sarcopenia in a community-dwelling older Japanese population. Moreover, subjects with sarcopenia had an increased mortality risk. Our findings suggest that a public health strategy for sarcopenia is needed to extend healthy life expectancy.
In the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) factorial trial, the combination of perindopril and indapamide reduced ...mortality among patients with type 2 diabetes, but intensive glucose control, targeting a glycated hemoglobin level of less than 6.5%, did not. We now report results of the 6-year post-trial follow-up.
We invited surviving participants, who had previously been assigned to perindopril-indapamide or placebo and to intensive or standard glucose control (with the glucose-control comparison extending for an additional 6 months), to participate in a post-trial follow-up evaluation. The primary end points were death from any cause and major macrovascular events.
The baseline characteristics were similar among the 11,140 patients who originally underwent randomization and the 8494 patients who participated in the post-trial follow-up for a median of 5.9 years (blood-pressure-lowering comparison) or 5.4 years (glucose-control comparison). Between-group differences in blood pressure and glycated hemoglobin levels during the trial were no longer evident by the first post-trial visit. The reductions in the risk of death from any cause and of death from cardiovascular causes that had been observed in the group receiving active blood-pressure-lowering treatment during the trial were attenuated but significant at the end of the post-trial follow-up; the hazard ratios were 0.91 (95% confidence interval CI, 0.84 to 0.99; P=0.03) and 0.88 (95% CI, 0.77 to 0.99; P=0.04), respectively. No differences were observed during follow-up in the risk of death from any cause or major macrovascular events between the intensive-glucose-control group and the standard-glucose-control group; the hazard ratios were 1.00 (95% CI, 0.92 to 1.08) and 1.00 (95% CI, 0.92 to 1.08), respectively.
The benefits with respect to mortality that had been observed among patients originally assigned to blood-pressure-lowering therapy were attenuated but still evident at the end of follow-up. There was no evidence that intensive glucose control during the trial led to long-term benefits with respect to mortality or macrovascular events. (Funded by the National Health and Medical Research Council of Australia and others; ADVANCE-ON ClinicalTrials.gov number, NCT00949286.).
There is no consensus on the importance of visit-to-visit glycemic variability in diabetes. Therefore, we assessed the effects of visit-to-visit variability (VVV) in HbA1c and fasting glucose on ...major outcomes in the ADVANCE (Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation) trial.
ADVANCE was a factorial randomized controlled trial of intensive glucose control and blood pressure lowering in patients with type 2 diabetes. VVV in the intensive glucose treatment group was defined using the SD of five measurements of HbA1c and glucose taken 3-24 months after randomization. Outcomes were combined macro- and microvascular events and all-cause mortality occurring post 24 months. Sensitivity analyses were performed using other indices of variability and in the standard glucose treatment group.
Among 4,399 patients in the intensive group, an increase in VVV of HbA1c was associated with an increased risk of vascular events (P = 0.01) and with mortality (P < 0.001): highest versus lowest tenth hazard ratio (95% CI) 1.64 (1.05-2.55) and 3.31 (1.57-6.98), respectively, after multivariable adjustment. A clear association was also observed between VVV of fasting glucose and increased risk of vascular events (P < 0.001; 2.70 1.65-4.42). HbA1c variability was positively associated with the risk of macrovascular events (P = 0.02 for trend), whereas glucose variability was associated with both macro- and microvascular events (P = 0.005 and P < 0.001 for trend, respectively). Sensitivity analyses using other indices, and patients in the standard glucose treatment group, were broadly consistent with these results.
Consistency of glycemic control is important to reduce the risks of vascular events and death in type 2 diabetes.
Background:Atrial fibrillation (AF) is a common arrhythmia in the elderly, and causes complications such as cardioembolic stroke. Serum high-sensitivity C-reactive protein (hs-CRP), a marker of ...systemic inflammation, has been reported to be a risk factor for developing AF in Western countries. However, few community-based studies have examined this issue in general Asian populations.Methods and Results:A total of 2,510 community-dwelling Japanese participants aged ≥40 years without a history of AF were divided into 4 groups according to the sex-specific quartiles of serum hs-CRP concentrations (Q1, lowest and Q4, highest) and followed up for 24 years. The hazard ratios and their 95% confidence intervals for the development of AF were estimated using a Cox proportional hazards model. During the follow up, 234 subjects developed AF. The risk of AF increased significantly with elevating serum hs-CRP levels after adjustment for potential confounding factors (hazard ratio 95% confidence interval, Q1, 1.00 reference; Q2, 1.26 0.83–1.92; Q3, 1.77 1.18–2.66; and Q4, 1.89 1.24–2.86; P for trend <0.001).Conclusions:The study findings suggest that elevated serum hs-CRP levels are an independent risk factor for the development of AF in a general Japanese population.
Aims/hypothesis
Our aim was to compare the contributions of impaired beta cell function (IBF) and insulin resistance with the development of type 2 diabetes in a Japanese community.
Methods
A total ...of 2094 residents aged 40–79 years without diabetes underwent a health examination including a 75 g OGTT in 2007. Participants were divided into four groups according to the presence or absence of IBF (insulinogenic index/HOMA-IR ≤28.5) and insulin resistance (HOMA-IR ≥1.61) and were followed up for 7 years (2007–2014). Cox’s proportional hazards model was used to estimate HRs and 95% CIs for type 2 diabetes. The population attributable fractions (PAFs) due to IBF, insulin resistance, and their combination were calculated.
Results
At baseline, the prevalence of isolated IBF, isolated insulin resistance, and both IBF and insulin resistance were 5.4%, 24.1% and 9.5%, respectively. During the follow-up period, 272 participants developed type 2 diabetes. The multivariable-adjusted HRs (95% CI) and PAFs (95% CI) for type 2 diabetes were 6.3 (4.3, 9.2) and 13.3% (8.7, 17.7) in the participants with isolated IBF, 1.9 (1.3, 2.7) and 10.5% (4.0, 16.6) in those with isolated insulin resistance, and 8.0 (5.7, 11.4) and 29.3% (23.0, 35.1) in those with both IBF and insulin resistance, respectively, compared with the participants without either.
Conclusions/interpretation
The present study suggests that the combination of IBF and insulin resistance makes the main contribution to the development of type 2 diabetes in Japanese communities.
Graphical abstract
Aim: Secular trends in the risk of recurrent stroke have been reported in several epidemiological studies worldwide, but this issue has not been investigated in general Japanese populations. We ...examined the trends in the 5-year risk of recurrent stroke over a half century using community-based prospective data in Japan.Methods: We established 4 cohort studies in 1961, 1974, 1988, and 2002. To examine the risk of recurrent stroke, participants who developed stroke during a 10-year follow-up period in each cohort were followed-up for 5 years from the date of first onset. A total of 154 (first sub-cohort: 1961-1971), 144 (second sub-cohort: 1974-1984), 172 (third sub-cohort: 1988-1998), and 146 (fourth sub-cohort: 2002-2012) participants from each cohort were enrolled in the present study. The 5-year cumulative risk of recurrent stroke was compared among the sub-cohorts using the Kaplan-Meier method and the age- and sex-adjusted Cox proportional hazards model.Results: The risks of recurrent stroke after any stroke and ischemic stroke decreased significantly from the first to the third sub-cohort, but they did not clearly change from the third to the fourth sub-cohort. The risk of recurrent stroke after hemorrhagic stroke decreased mainly from the first to the second sub-cohort and there was no apparent decrease from the second to the fourth sub-cohort. These trends were substantially unchanged after adjusting for age and sex.Conclusions: In the Japanese community, the risk of recurrent stroke decreased mainly from the 1960s to 1990s, but there was no apparent decrease in recent years.
Background:Growing evidence suggests that high serum uric acid (SUA) levels are causally related to increased risk of chronic kidney disease (CKD). However, few studies have investigated the ...influence of elevated SUA levels on the incidence of kidney dysfunction and albuminuria separately in community-based populations.Methods and Results:A total of 2,059 community-dwelling Japanese subjects aged ≥40 years without CKD were followed for 5 years. CKD was defined as kidney dysfunction (estimated glomerular filtration rate <60 ml/min/1.73 m2) or albuminuria (urine albumin-creatinine ratio ≥30 mg/g). The odds ratio (OR) for the development of CKD was estimated according to quartiles of SUA (≤4.0, 4.1–4.9, 5.0–5.8, and ≥5.9 mg/dl). During the follow-up, 396 subjects developed CKD, of whom 125 had kidney dysfunction and 312 had albuminuria. The multivariable-adjusted risk of developing CKD increased with higher SUA levels (OR 1.00 reference for ≤4.0, 1.21 95% confidence interval, 0.84–1.74 for 4.1–4.9, 1.47 1.01–2.17 for 5.0–5.8, and 2.10 1.37–3.23 for SUA ≥5.9 mg/dl, respectively). Similarly, there were positive associations between SUA level and the adjusted risk of developing kidney dysfunction (OR 1.00 reference, 2.30 1.10–4.82, 2.81 1.34–5.88, and 3.73 1.65–8.44) and albuminuria (1.00 reference, 1.12 0.76–1.65, 1.35 0.90–2.03, and 1.81 1.14–2.87, respectively).Conclusions:Higher SUA levels were a significant risk factor for the development of both kidney dysfunction and albuminuria in a general Japanese population. (Circ J 2016; 80: 1857–1862)
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