Motoyuki Nakamura

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

BACKGROUNDnHigh 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.nnnMETHODSnThe 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.nnnRESULTSnDuring 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).nnnCONCLUSIONnCRP 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.

OBJECTIVEnStructural 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.nnnMETHODSnSubjects 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.nnnRESULTSnDuring 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).nnnCONCLUSIONnElevated plasma BNP levels predict the risk of ischemic stroke within men from the general population.

Influence of the Great East Japan Earthquake and Tsunami 2011 on Occurrence of Cerebrovascular Diseases in Iwate, Japan

Background and Purpose— Little information is available regarding the occurrence of cerebrovascular diseases after tsunamis. This study was performed to determine the influence of the tsunami damage caused by the Great East Japan earthquake on occurrence of cerebrovascular diseases. Methods— Subjects from the coastline and inland areas of Iwate Prefecture who developed cerebrovascular diseases before and after the disaster were included in the analysis. Standardized incidence ratios of 2011 against the previous 3 years were calculated in two 4-week periods before and four 4-week periods after the disaster, according to stroke subtype, sex, age group, and flood damage. Results— The standard incidence ratio for cerebrovascular diseases was 1.20 (1.00–1.40) in the first 4-week period after the disaster and was not significant in other periods. The standard incidence ratios in the first 4-week period for cerebral infarction, intracerebral hemorrhage, and subarachnoid hemorrhage were 1.22 (0.98–1.46), 1.15 (0.76–1.55), and 1.20 (0.52–1.88), respectively. These values were 1.51 (1.19–1.88) for men, 1.35 (1.06–1.64) for subjects aged ≥75 years, and 1.35 (1.06–1.64) for the high flooding areas. The standard incidence ratio of cerebral infarction in the first 4-week period for men aged ≥75 years in the high flooding areas was 2.34 (1.34–3.34). Conclusions— In the areas highly flooded by the tsunami caused by the Great East Japan earthquake, the occurrence of cerebral infarction among elderly men more than doubled in the first 4 weeks after the disaster.

Cardiovascular risk factors in the Japanese northeastern rural population

BACKGROUNDnPeople living in the northeastern part of Japan have high prevalences of hypertension and stroke. The current status of cardiovascular risk factors in them should be elucidated.nnnMETHODSnThe survey was carried out from 2002 to 2004 in the northeastern part of the main island of Japan. A total of 26,472 Japanese men and women were enrolled (acceptance rate: 84.5%). Sex- and age-specific prevalences of cardiovascular risk factors were determined. Mean values of predictive markers (high-sensitivity C reactive protein (hsCRP), brain natriuretic peptide (BNP) and microalbuminuria) were also determined in each group. Risk factor-related variables in non-hypertensive subjects and hypertensive subjects were compared.nnnRESULTSnProportions of subjects with hypertension, diabetes and dyslipidemia were 46.0%, 7.6%, and 30.3%, respectively, in males and 38.6%, 4.0%, and 38.5%, respectively, in females. Mean values of hsCRP and BNP were 1.41 mg/L and 26.5 pg/mL, respectively, in males and 1.01 mg/L and 23.7 pg/mL, respectively, in females. Proportions of male and female subjects with microalbuminuria were 22.0% and 23.4%, respectively. These markers become higher with advance of age. Prevalence of atrial fibrillation was 1.56%, and it increased with advance of age in both men and women. High prevalences of cardiovascular risk factors in this area were found. Hypertensive subjects who did not take anti-hypertension medication accounted for about 20% of total subjects and their blood pressure remained poorly controlled.nnnCONCLUSIONnAttention should be given to cardiovascular risk factors in the Japanese northeastern rural population.

NLRP3 inflammasome activation in coronary artery disease: results from prospective and randomized study of treatment with atorvastatin or rosuvastatin.

The NLRP-3 (nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3) inflammasome has recently emerged as a pivotal regulator of chronic inflammation. The aim of the present study was to determine whether NLRP3 inflammasome is expressed in patients with CAD (coronary artery disease) and whether statins (atorvastatin or rosuvastatin) might affect NLRP3 levels. In an inxa0vitro study, human THP-1 cells treated with statins were analysed for NLRP3 inflammasome levels. The present study included 60 patients with CAD and 30 subjects without CAD (non-CAD). Patients with CAD randomly received either 8 months of treatment with atorvastatin or rosuvastatin. PBMCs (peripheral blood mononuclear cells) were obtained from peripheral blood at baseline and after 8 months of statin therapy. Levels of NLRP3 inflammasome, IL (interleukin)-1β and IL-18 were measured by real-time RT-PCR (reverse transcription-PCR) and FACS. Levels of NLRP3 inflammasome were higher in the CAD group than in the non-CAD group. There was a positive correlation between NLRP3 inflammasome and cytokines (IL-1β and IL-18) levels. A randomized clinical study has shown that atorvastatin markedly diminished NLRP3 inflammasome levels, whereas rosuvastatin had no impact on these levels. Levels of NLRP3 inflammasome decreased in THP-1 cells treated with statins compared with those treated with vehicle, and the fold changes in NLRP3 inflammasome were higher in THP-1 cells treated with atorvastatin compared with those treated with rosuvastatin. The present study suggests that atorvastatin down-regulates NLRP3 inflammasome expression in CAD, possibly contributing to the inhibitory effects of atorvastatin on chronic inflammation and atherogenic progression in this disorder.

Comparison of low-density lipoprotein cholesterol concentrations measured by a direct homogeneous assay and by the Friedewald formula in a large community population

BACKGROUNDnWe compare the direct homogeneous low-density lipoprotein cholesterol (LDL-C) assay with the Friedewald formula (FF) for determination of LDL-C in a large community-dwelling population.nnnMETHODSnA total of 21,194 apparently healthy subjects aged 40 to 79 years with triglyceride (TG) concentrations <4.52 mmol/l were enrolled. LDL-C were directly measured by the enzymatic homogeneous assay (LDL-C (D)) and also estimated by the FF (LDL-C (F)). Paired t-test, Pearsons correlation coefficient and linear regression analysis were performed and the concordances of the National Cholesterol Education Program (NCEP) risk category were estimated.nnnRESULTSnBoth in fasting (n=3270) and nonfasting samples (n=17,924), LDL-C (D) highly correlated with LDL-C (F): r=0.971 and 0.955, respectively. Concordant results for NCEP categories were 84.8% for fasting samples and 80.1% for nonfasting samples. However, the bias between the 2 measurements increased in samples with TG concentrations >1.69 mmol/l, especially in nonfasting samples.nnnCONCLUSIONSnThe results showing less variability of the direct LDL-C assay than that of the FF in nonfasting samples suggest that epidemiological studies can use LDL-C measured by the direct assay both in fasting and nonfasting samples.

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.

Dietary intake of n-3 polyunsaturated fatty acids is inversely associated with CRP levels, especially among male smokers

OBJECTIVEnTo examine whether dietary intake of n-3 polyunsaturated fatty acid (n-3PUFA) is associated with serum C-reactive protein (CRP) levels with regard to smoking status in the Japanese general population in a cross-sectional study.nnnMETHODS AND RESULTSnA total of 14,191 participants aged 40-69 years were enrolled and divided into quartile groups according to their intake of n-3PUFA. Multivariate-adjusted logarithm-transformed CRP levels were compared between the quartile groups with regard to smoking status after adjusting for traditional risk factors and intake of saturated fatty acids. Adjusted CRP levels were inversely associated with dietary intake of n-3PUFA for both the male subjects and female subjects (p<0.05 for trend). A linear trend was not seen between intake of n-3PUFA and adjusted CRP levels in male nonsmokers. Adjusted CRP level in the lowest quartile group of n-3PUFA was significantly higher than the levels in other groups in male smokers.nnnCONCLUSIONnSufficient dietary intake of n-3PUFA may attenuate inflammatory reaction and this effect is more evident among high-risk populations such as male smokers although the small numbers of female ex-smokers and nonsmokers limited statistical power to draw strong conclusions about these groups.

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.

Standardized Prevalence Ratios for Chronic Hepatitis C Virus Infection Among Adult Japanese Hemodialysis Patients

Background Many studies have estimated the prevalence of anti-hepatitis C virus (HCV) antibody among hemodialysis (HD) patients; however, the prevalence of HCV core antigen—which indicates the presence of chronic HCV infection—is not known. Methods Standardized prevalence ratios (SPRs) for anti-HCV antibody and HCV core antigen among HD patients (n = 1214) were calculated on the basis of data from the general population (n = 22 472) living in the same area. Results The prevalences of anti-HCV antibody and HCV core antigen were 12.5% and 7.8%, respectively, in male hemodialysis patients, and 8.5% and 4.1% in female hemodialysis patients. The SPRs (95% confidence interval) for anti-HCV antibody and HCV core antigen were 8.39 (6.72–10.1) and 12.9 (9.66–16.1), respectively, in males, and 5.42 (3.67–7.17) and 8.77 (4.72–12.8) in females. Conclusions The prevalences of chronic HCV infection among male and female HD patients were 13-fold and 9-fold, respectively, those of the population-based controls. Further studies should therefore be conducted to determine the extent of chronic HCV infection among HD patients in other populations and to determine whether chronic HCV infection contributes to increased mortality in HD patients.