Fumitaka Tanaka

Serum C-reactive protein levels can be used to predict future ischemic stroke and mortality in Japanese men from the general population

BACKGROUND High C-reactive protein (CRP) levels have been reported to be associated with an increased risk of atherosclerotic cardiovascular events. The relationship of CRP levels to the risk of cerebrovascular events in the Japanese population, which has a lower prevalence of coronary artery disease and a lower CRP level than Western populations, has not been fully clarified. The present study examined the predictive value of serum high sensitivity CRP (hs-CRP) levels for future cerebrovascular events and mortality in the general Japanese population. METHODS The subjects for this community-based, prospective cohort study were recruited from the general population (n=7901, male only, mean age=64.0 years). Serum hs-CRP levels and cardiovascular risk factors were determined at baseline. The mean follow-up period was 2.7 years. After excluding subjects with a cardiovascular history, the relationships between hs-CRP levels and cerebrovascular events and mortality were assessed. RESULTS During follow-up, 130 participants had a first stroke (95 ischemic strokes), and 161 participants died. The hs-CRP tertile level was a significant predictor for a first ischemic stroke (3rd tertile, HR=1.77: 95% Cl, 1.04-3.03, compared with the 1st tertile), after adjustment for age and classical cardiovascular risk factors. Similar trends were observed for the prediction of all-cause mortality (3rd tertile, HR=2.26: 95% Cl, 1.49-3.42, compared with the 1st tertile). CONCLUSION CRP levels can be used to predict future ischemic stroke and mortality in Japanese men from the general population, independently from traditional cardiovascular risk factors.

Predictive value of plasma B-type natriuretic peptide for ischemic stroke: a community-based longitudinal study.

OBJECTIVE Structural heart diseases including atrial fibrillation are precursors for ischemic stroke. Plasma B-type natriuretic peptide (BNP) has been reported to be increased in patients with several types of structural heart diseases. However, the predictive value of plasma BNP for ischemic stroke remains unknown. We have studied the predictive ability of plasma BNP for future development of stroke in community dwelling adults. METHODS Subjects of this community-based study were recruited from the general population (n=13,466). Plasma BNP levels and cardiovascular risk factors were determined at baseline. The incidence of ischemic stroke in the cohort was identified from regional stroke registry data. A multivariate Cox regression analysis was performed to analyze the relationship between plasma BNP levels and the risk of stroke. RESULTS During a mean follow-up period of 2.8 years, 102 participants (65 males, 37 females) experienced a first ischemic stroke. In men, after adjustment for classical cardiovascular risk factors and atrial fibrillation, the hazard ratio (HR) for ischemic stroke was significantly elevated in the highest plasma BNP quartile (HR=2.38; 95% CI=1.07-5.29). In women, the relationship between plasma BNP levels and risk of ischemic stroke was of marginal significance after adjusting for the presence or absence of atrial fibrillation (HR=3.03; 95% CI=0.84-10.92, P=0.09). CONCLUSION Elevated plasma BNP levels predict the risk of ischemic stroke within men from the general population.

Comparison of the Incidence of Acute Decompensated Heart Failure Before and After the Major Tsunami in Northeast Japan

On March 11, 2011, a huge tsunami attacked the northeastern coast of Japan after a magnitude 9 earthquake. No reports have investigated the impact of tsunamis on the incidence of cardiovascular disease, especially heart failure (HF). We investigated the number and clinical characteristics of hospitalized patients with acute decompensated HF (ADHF) in the east coast of Iwate hit by the tsunami (tsunami area) for a 12-week period around the disaster. For comparison with previous years, numbers of ADHF were surveyed in the corresponding area in 2009 and 2010. In addition, to elucidate the impact of the tsunami, a similar study was performed in a remote area where the tsunami had minimal effect (control area). After the disaster, the number of patients with ADHF in the tsunami area was significantly increased compared to the predisaster period (relative risk 1.97, 95% confidence interval 1.50 to 2.59). The peak was found 3 to 4 weeks after the disaster. In contrast, in the control area, no significant change in ADHF events was observed (relative risk 1.29, 95% confidence interval 0.94 to 1.78). There was a significant correlation between changes in the number of ADHF admissions and percent tsunami flood area (r = 0.73, p <0.001) or the number of shelter evacuees (r = 0.83, p <0.001). In conclusion, these findings suggest that large and sudden changes in daily life and the trauma associated with a devastating tsunami have a significant impact on the incidence of ADHF.

Population-Based Incidence of Sudden Cardiac and Unexpected Death Before and After the 2011 Earthquake and Tsunami in Iwate, Northeast Japan

Background The aim of this study was to evaluate the temporal impact of the 2011 Japan earthquake and tsunami on the incidence of sudden cardiac and unexpected death (SCUD). Methods and Results We surveyed the impact of the disaster on the incidence and clinical characteristics of SCUD in Iwate. To perform complete identification of SCUD for 8 weeks before and 40 weeks after the disaster, medical records and death certificates relevant to SCUD were surveyed in the study area. Compared with the previous years rate, the incidence (per 10 000 person‐year) of SCUD for the initial 4 weeks after the disaster (acute phase) was double (33.5 vs 18.9), and thereafter the rate returned to the previous level. Significant relationships were found between weekly numbers of SCUD and seismic activity (intensity, r=0.43; P<0.005: frequency, r=0.46; P<0.002). The standardized incidence ratio (SIR) of SCUD in the acute phase was significantly increased compared with that of previous years (1.71, 95% CI 1.33 to 2.16). Increased SIRs were predominantly found in female subjects (1.73, 95% CI 1.22 to 2.37), the elderly (1.73, 95% CI 1.29 to 2.27), and residents living in the tsunami‐stricken area (1.83, 95% CI 1.33 to 2.46). In addition, SIRs for weekdays (1.71, 95% CI 1.28 to 2.24) and nights‐mornings (2.09, 95% CI 1.48 to 2.86) were amplified. Conclusions The present results suggest that the magnitude of a disaster, related stress, and population aging may cause a temporary increase in the incidence of SCUD with amplification of ordinary weekly and circadian variations.

Poor self-rated health is significantly associated with elevated C-reactive protein levels in women, but not in men, in the Japanese general population

OBJECTIVE Self-rated health (SRH) is associated with risk for mortality, but its biological basis is poorly understood. We examined the association between SRH and low-grade inflammation in a Japanese general population. METHODS A total of 5142 men and 11,114 women aged 40 to 69years were enrolled. SRH was assessed by a single question and classified into four categories: good, rather good, neither good nor poor, and poor. Serum high-sensitivity C-reactive protein (hsCRP) levels were measured by the latex-enhanced immunonephelometric method. Elevated CRP was defined as hsCRP level of 1.0mg/L or higher. The association between SRH and elevated CRP was evaluated by using logistic regression with adjustment for age, socioeconomic status (job status, education and marital status), health-related behaviors (smoking status, drinking status, exercise habits and sleep duration), and cardiovascular risk factors (body mass index, systolic blood pressure, total- and HDL-cholesterol, HbA1c and prevalent stroke and/or myocardial infarction). RESULTS Compared to persons with good SRH, persons with poor SRH had significantly higher risk for elevated CRP: age-adjusted ORs (95% CIs) were 1.33 (1.01-1.76) in men and 1.66 (1.36-2.02) in women. The significant association remained even after adjustment for socioeconomic status, health-related behaviors and cardiovascular risk factors in women, whereas the significance disappeared in men. CONCLUSION Poor SRH is associated with low-grade inflammation in both sexes. In women, but not in men, the association is independent of potential confounders. These findings provide an insight into the biological background of SRH in a general population.

Prehypertension Subtype With Elevated C-Reactive Protein: Risk of Ischemic Stroke in a General Japanese Population

BACKGROUND Prehypertension (PreHT) and low-grade inflammation are both known to be related to the incidence of cardiovascular events. This cohort study investigated whether the high-risk group for future ischemic stroke among PreHT subjects can be predicted by stratification of high-sensitivity C-reactive protein (hsCRP). METHODS A total of 22,676 subjects aged 40-80 years from the general population who had no cardiovascular history underwent baseline measurement of serum hsCRP, and were followed for the incidence of ischemic stroke. RESULTS During the mean follow-up period of 2.7 years, 143 subjects had a first ischemic stroke. In a Cox multivariable model after adjustment for cardiovascular risk factors, there was no significant difference in hazard ratio (HR) for incidence of ischemic stroke between the normotension (NT) and PreHT subjects (HR = 1.72, 95% confidence interval (CI): 0.93-3.18, vs. NT subjects). In contrast, the HR for incidence of ischemic stroke in PreHT subjects with higher hsCRP levels (≥0.5 mg/l in men, ≥0.4 mg/l in women, more than median levels according to sex) was increased compared to NT subjects with lower hsCRP levels (HR = 2.63, 95% CI: 1.11-6.24). Moreover, the HR for incidence of ischemic stroke in PreHT subjects with lower CRP levels (HR = 0.91, 95% CI: 0.31-2.73) did not differ from that in NT subjects with lower hsCRP levels. CONCLUSIONS This study showed that, in a Japanese general population, hsCRP was a marker for relatively short-term risk of ischemic stroke in PreHT subjects.

High risks of all-cause and cardiovascular deaths in apparently healthy middle-aged people with preserved glomerular filtration rate and albuminuria: A prospective cohort study

BACKGROUND The reason why coexistence of preserved estimated glomerular filtration rate (eGFR) and albuminuria contributes to a high risk of death and which cause of death increases all-cause mortality have not been elucidated. METHODS A total of 16,759 participants aged 40 to 69 years with normal or mildly reduced eGFR (45-119 ml/min/1.73 m(2)) were enrolled and divided into six groups (group 1, eGFR: 90-119 without albuminuria; group 2, eGFR: 90-119 with albuminuria; group 3, eGFR: 60-89 without albuminuria (reference); group 4, eGFR: 60-89 with albuminuria; group 5, eGFR: 45-59 without albuminuria; group 6, eGFR: 45-59 with albuminuria) based on GFR estimated by using the CKD-EPI study equation modified by a Japanese coefficient and albuminuria (urine albumin-creatinine ratio ≥ 30 mg/g). Outcomes included all-cause death (ACD), cardiovascular death (CVD) and neoplasm-related death (NPD). Multivariable-adjusted mortality rate ratios (RR) and their 95% confidence intervals (CIs) in the groups were estimated by Poissons regression analysis. RESULTS The highest risk of ACD (RR (95% CIs): 3.95 (2.08-7.52)), CVD (7.15 (2.25-22.7)) and NPB (3.25 (1.26-8.38)) was observed in group 2. Subjects in group 2 were relatively young and had the highest levels of body mass index, blood pressure and HbA1c and the highest prevalence of diabetes and metabolic syndrome. CONCLUSION Coexistence of preserved eGFR and albuminuria increases risks for ACD, CVD and NPD. Relatively young metabolic persons having both preserved eGFR and albuminuria should be considered as a very high-risk population.

Low-grade albuminuria and incidence of cardiovascular disease and all-cause mortality in nondiabetic and normotensive individuals.

Background: Recent studies indicate that, in people with diabetes or hypertension and in the general population, low-grade albuminuria (LGA) below the microalbuminuria threshold is a predictor for incidence of cardiovascular disease (CVD) and mortality. However, it remains unclear whether LGA predicts the risk of CVD incidence and death in nondiabetic and normotensive individuals. Methods: A total of 3599 individuals aged not less than 40 years from the general population who are free of CVD in nondiabetic and normotensive individuals with preserved glomerular filtration rate were followed for CVD incidence and all-cause death. LGA was defined as urinary albumin to creatinine ratio (UACR) less than 30 mg/g. It was examined whether there is an association between LGA and CVD incidence or all-cause death. Results: During the average 5.9 years of follow-up, 61 individuals had first CVD events, and 85 individuals died. The hazard ratios (HRs) for CVD incidence and all-cause death after full adjustment by potential confounders increased significantly in the top tertile of LGA (UACR ≥ 9.6 mg/g for men, ≥ 12.0 mg/g for women) compared with the first tertile [HR = 2.79, 95% confidence interval (CI), 1.41–5.52, HR = 1.69, 95% CI, 1.00–2.84, respectively]. Population-attributable fractions of the top tertile of LGA for CVD incidence and all-cause death were 37.9 and 20.1%, respectively. Conclusion: In apparently healthy individuals with optimal blood pressure and no diabetes, LGA independently predicts CVD incidence and all-cause death, particularly with the large contribution to the excessive incidence of CVD.

Gender-specific risk stratification with plasma B-type natriuretic peptide for future onset of congestive heart failure and mortality in the Japanese general population.

BACKGROUND Elevated plasma B-type natriuretic peptide (BNP) levels suggest a high risk for future onset of cardiovascular events including congestive heart failure (CHF) and mortality. In the general population, although median plasma BNP levels have been reported to be higher in women than in men, the incidence of CHF and mortality are lower in women. However, no studies have examined gender-specific risk stratification of plasma BNP levels for future onset of CHF and mortality. METHODS Subjects of this study were recruited from our general population. Baseline data including plasma BNP were determined in 13,466 subjects (men 4527, women 8939; median age = 64 yrs). A multivariate Cox regression analysis was performed to examine the predictive ability of plasma BNP for new onset of CHF and mortality. RESULTS The mean follow-up duration was 2.9 years. After adjustment for traditional cardiovascular risk factors including atrial fibrillation, hazard ratios for CHF development for values above the 75th percentile of BNP were 13.4 (p<0.001) in men and 8.5 (p<0.001) in women. Similarly, each increment of 1SD in log BNP levels increased the hazard ratio by 8.8 (p<0.001) in men, and 6.7 (p<0.001) in women. The area under the receiver operating characteristic curve was significant for prediction of the onset of CHF (men; 0.853, women; 0.838). In addition, increased plasma BNP levels implied high risk of any-cause mortality in men (above the 75th percentile; hazard ratio = 1.8, p=0.005: increment of 1SD; hazard ratio = 1.4, p=0.024), but this relationship was suboptimal in women. CONCLUSION Measurements of plasma BNP provides strong predictive information about future onset of CHF in both sexes, with predictive ability for death being effective especially in men.

Sex-Specific Threshold Levels of Plasma B-Type Natriuretic Peptide for Prediction of Cardiovascular Event Risk in a Japanese Population Initially Free of Cardiovascular Disease

Elevated plasma B-type natriuretic peptide (BNP) levels have been reported to be related to a high risk for cardiovascular (CV) disease in the general population. However, there has been no accurate determination of the threshold levels of plasma BNP that indicate an increased potential for the development of general CV events (i.e., heart failure, stroke, and myocardial infarction) and the validity of these levels for predicting CV events compared to classic risk markers. To establish gender-specific thresholds of plasma BNP levels associated with increased risk for CV disease in the general population, baseline BNP levels were determined in community-dwelling adults (n = 13,209, mean age 62 ± 10 years,) and CV events in the cohort were captured prospectively. The cohort was divided by deciles of plasma BNP level in each gender. A Cox proportional-hazards model was used to determine the relative hazard ratios among the deciles. In addition, to compare the utility of plasma BNP to the Framingham 10-year risk score for predicting general CV events, receiver-operating characteristic analysis was performed. During follow-up, CV events were identified in 429 patients in the cohort. Compared to the reference decile level (first to fourth), the hazard ratio was significantly increased from the ninth decile in men (greater than approximately 37 pg/ml) and the highest decile in women (greater than approximately 55 pg/ml). The area under the curve generated on receiver-operating characteristic analysis of plasma BNP testing was comparable to that for the Framingham risk scoring system (0.67 vs 0.68 in men, 0.63 vs 0.68 in women; p = NS for both). In conclusion, within a community-based general population with no CV history, plasma BNP levels higher than defined thresholds show increased risk for general CV events, and the predictive ability for CV events occurring within several years may be comparable to that of an established long-standing risk score.