High Parity Is an Independent Risk Factor for Tooth Loss in Women: A Community-Based Takahata Study in Japan.

Risk factors for tooth loss have been widely examined previously. However, no previous study has comprehensively investigated the risk factors, including lifestyle-related specific factors (parity, oral health habits, and socioeconomic status), for fewer than 20 teeth among women in the general population in Japan. This cross-sectional study explored the association of these risk factors, especially parity, with having fewer than 20 teeth among Japanese women. A self-reported questionnaire including items on lifestyle-related risk factors (parity, oral health, diet [e.g., alcohol and sucrose consumption]) and socioeconomic status was sent by post to female residents (age ≥ 40 years) of Takahata town, Yamagata Prefecture, in 2005. Multivariate logistic regression analysis including 3,854 eligible participants was performed to investigate the association between various factors (including parity) and having fewer than 20 teeth. The results indicated that, compared with nulliparous women, women with two, three, and four completed pregnancies had 2.485-, 2.844-, and 4.305-fold increased risk of having fewer than 20 teeth, respectively. Our study is the largest-scale study of the general female population in Japan and the first study to comprehensively investigate risk factors (parity, oral health status, and socioeconomic status) for fewer than 20 teeth. We thus found that higher parity, especially, two or more, was independent risk factors for having less than 20 teeth among Japanese women. In conclusion, the present study emphasizes the importance of good oral health habits in women, especially, during pregnancy and in the postpartum period, to maintain 20 or more teeth.

Growth Factor Midkine Aggravates Pulmonary Arterial Hypertension via Surface Nucleolin.

Pulmonary arterial hypertension (PAH) is a progressive fatal disease caused by pulmonary arterial remodeling. Midkine regulates cell proliferation and migration, and it is induced by hypoxia, but its roles in pulmonary arterial remodeling remain unclear. Serum midkine levels were significantly increased in PAH patients compared with control patients. Midkine expression was increased in lungs and sera of hypoxia-induced PAH mice. Hypoxia-induced pulmonary arterial remodeling and right ventricular hypertrophy were attenuated in midkine-knockout mice. Midkine-induced proliferation and migration of pulmonary arterial smooth muscle cells (PASMC) and epidermal growth factor receptor (EGFR) signaling were significantly increased under hypoxia, which also induced cell-surface translocation of nucleolin. Nucleolin siRNA treatment suppressed midkine-induced EGFR activation in vitro, and nucleolin inhibitor AS1411 suppressed proliferation and migration of PASMC induced by midkine. Furthermore, AS1411 significantly prevented the development of PAH in Sugen hypoxia rat model. Midkine plays a crucial role in PAH development through interaction with surface nucleolin. These data define a role for midkine in PAH development and suggest midkine-nucleolin-EGFR axis as a novel therapeutic target for PAH.

The Landscape Montage Technique for diagnosing frontotemporal dementia starting as primary progressive aphasia: a case report.

BACKGROUND: The Landscape Montage Technique was originally developed by Hisao Nakai, a Japanese psychiatrist, to pursue the possibility and application of a psychotherapeutic approach using drawing for patients with schizophrenia. Drawing was initially adopted to evaluate patients with an impaired ability for verbal expression, particularly for the diagnosis and treatment of patients with schizophrenia. Since its development, the Landscape Montage Technique has been utilized in various clinical settings throughout Japan. This study aimed to evaluate the psychiatric conditions of a patient diagnosed as having primary progressive aphasia using the Landscape Montage Technique at a 3-year follow-up. CASE PRESENTATION: We present the case of a 64-year-old, right-handed Japanese woman initially diagnosed as having logopenic variant primary progressive aphasia or logopenic aphasia. At a 3-year follow-up, logopenic aphasia progressed to behavioral variant frontotemporal dementia or frontotemporal dementia. According to her husband, she began to have speech difficulties approximately 5 years before her first visit. The results of neurocognitive tests suggested mild cognitive impairment or early stages of dementia. Her clinical dementia rating score was 0.5, suggesting a diagnosis of mild cognitive impairment. She had a Raven's Colored Progressive Matrices score of 31 out of 36, which indicated a nonverbal cognitive ability that was greater than the 90th percentile for her age. The Japanese Standard Language Test of Aphasia, which was performed at two points during the follow-up, indicated the possibility for a diagnosis of primary progressive aphasia given the progression of her aphasia. Based on her clinical symptoms and Japanese Standard Language Test of Aphasia results, a diagnosis of logopenic variant primary progressive aphasia was established. Magnetic resonance imaging revealed severe predominant left frontal and anterior temporal atrophy, as well as bilateral parietal atrophy. Amyloid beta deposition was negative. At the 3-year follow-up, logopenic variant primary progressive aphasia had progressed to behavioral variant frontotemporal dementia. However, the Landscape Montage Technique allowed for the diagnosis of behavioral variant frontotemporal dementia only 2 years after baseline. CONCLUSIONS: The present study showed that the Landscape Montage Technique can be useful for diagnosing behavioral variant frontotemporal dementia that starts as logopenic variant primary progressive aphasia at earlier stages.

Cardiac Nuclear High-Mobility Group Box 1 Ameliorates Pathological Cardiac Hypertrophy by Inhibiting DNA Damage Response.

High-mobility group box 1 (HMGB1) is a deoxyribonucleic acid (DNA)-binding protein associated with DNA repair. Decreased nuclear HMGB1 expression and increased DNA damage response (DDR) were observed in human failing hearts. DNA damage and DDR as well as cardiac remodeling were suppressed in cardiac-specific HMGB1 overexpression transgenic mice after angiotensin II stimulation as compared with wild-type mice. In vitro, inhibition of HMGB1 increased phosphorylation of extracellular signal-related kinase 1/2 and nuclear factor kappa B, which was rescued by DDR inhibitor treatment. DDR inhibitor treatment provided a cardioprotective effect on angiotensin II-induced cardiac remodeling in mice.

The association between urinary sodium excretion and blood pressure in a community-based population: the Yamagata (Takahata) study.

BACKGROUND: The association between salt intake and blood pressure levels is still inconclusive, and may be influenced by patient characteristics. We thus conducted a community-based cross-sectional study. METHODS: This study included 2297 subjects aged ≥ 40 years not on antihypertensive medication at the time of a health check-up. We examined the association between blood pressure levels and the estimated amount of 24-h urinary sodium excretion (e24hUNa) stratified by background characteristics. The 24-h urinary excretion levels of sodium and potassium were estimated from Kawasaki's equation using a spot urine sample. RESULTS: The association of systolic blood pressure (SBP) and diastolic blood pressure (DBP) with e24hUNa was significantly positive in a multiple linear regression model adjusted for confounders including age, sex, smoking, alcohol consumption, body mass index, diabetes, hypercholesterolemia, renal function, and potassium excretion. The regression coefficients of changes in SBP and DBP per 1 SD increase in e24hUNa (53 mEq/day) were + 1.91 mmHg and + 0.94 mmHg, respectively. In the subgroup analyses, the increase in SBP was especially greater in the elderly, in subjects with diabetes, and in subjects with reduced renal function compared to those in the counterparts. The association between SBP and e24hUNa was insignificant in subjects with eGFR ≥ 90 ml/min/1.73m2, while the association with progression of renal dysfunction was stronger and significant. CONCLUSIONS: These results demonstrated that the association between blood pressure and urinary sodium excretion was strengthened by characteristics of subjects such as aging, presence of diabetes, and renal impairment in the community-based population.

Increased plasma xanthine oxidoreductase activity deteriorates coronary artery spasm.

Increased reactive oxygen species (ROS) contributes to the development of endothelial dysfunction, which is involved in coronary artery spasm (CAS). Xanthine oxidoreductase (XOR) plays a pivotal role in producing both uric acid and ROS. However, the association between plasma XOR activity and CAS has not been elucidated. The aim of this study was to investigate whether plasma XOR activity is associated with CAS. We measured XOR activity in 104 patients suspected for CAS, who presented without significant coronary artery stenosis and underwent intracoronary acetylcholine provocation tests. CAS was provoked in 44 patients and they had significantly higher XOR activity as compared with those without CAS. The patients were divided into three groups based on the XOR activity. The prevalence rate of CAS was increased with increasing XOR activity. A multivariate logistic regression analysis showed that the 3rd tertile group exhibited a higher incidence of CAS as compared with the 1st tertile group [odds ratio (OR) 6.9, P = 0.001) and the 2nd tertile group (OR 3.2, P = 0.033) after adjustment for conventional CAS risk factors, respectively. The C index was significantly improved by the addition of XOR activity to the baseline model based on CAS risk factors. Furthermore, the 3rd tertile group had the highest incidence of severe spasm defined as total obstruction, flow-limiting stenosis, diffuse spasm, multivessel spasm, and/or lethal arrhythmia. This is a first report to elucidate the association of plasma XOR activity with CAS. Increased plasma XOR activity is significantly associated with CAS.

Risk factors for tooth loss in community-dwelling Japanese aged 40 years and older: the Yamagata (Takahata) study.

OBJECTIVES: The aim of the present study was to investigate comprehensively the risk factors, including some lifestyle-associated factors, oral health habits, and socioeconomic status, for having less than 20 teeth in cross-sectional study in the general population of Japan. MATERIALS AND METHODS: The survey population was the general population of individuals aged greater than or equal to 40 years in Takahata town, Japan in 2005. A postal survey with a self-administered questionnaire was distributed, and 7542 participants were entered into the final statistical analysis. The self-administered questionnaire contained items regarding some lifestyle-associated factors, oral health, and dietary intake, including alcohol and sucrose consumption. To confirm the independent association between the number of teeth and several parameters, a multivariate logistic regression analysis was used to estimate the adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs). RESULTS: A low educational status, no dental check-ups, low frequency of brushing, older age, and smoking habit were independent risk factors for less than 20 teeth. A low educational status was a particularly significant risk factor for less than 20 teeth (OR = 1.352, 95% CI = 1.125-1.624). CONCLUSION: These results emphasize the importance of good oral health habits, such as frequent tooth brushing, routine dental check-ups, and no smoking, and indicate that more appropriate and compulsory education regarding oral health is needed to lessen the education level-derived differences in oral health. CLINICAL RELEVANCE: Poor oral health habits and low educational status are the independent risk factors for having less than 20 teeth.

Fewer teeth are a risk factor for being underweight in community-dwelling Japanese aged 40 years and older: The Yamagata (Takahata) Study.

OBJECTIVE: The aim of the present study was to investigate comprehensively, the risk factors for underweight in cross-sectional study in the general population of Japan. METHODS: The survey population was the general population of individuals aged >40 years in Takahata town, Japan in 2005. A postal survey in the form of a self-administered questionnaire was distributed, and 6084 individuals were entered into the final statistical analysis. The self-administered questionnaire contained items regarding lifestyle, oral health status, socio-economic status and dietary intake. To examine the independent relationships between an underweight status and several parameters, a multivariate logistic regression analysis was used to estimate adjusted odds ratios (ORs). RESULTS: The number of teeth, age, alcohol consumption, hypertension, spousal status, smoking habit, appetite, body weight at 20 years of age, habit of going out and physical activity were independently associated with an underweight status compared with the normal weight group. Individuals with fewer than 10 teeth were especially more likely to be underweight than individuals with more than 20 teeth (OR = 1.956, 95% CI = 1.261-3.035). CONCLUSION: This study showed an independent association between the number of teeth and an underweight status, indicating that fewer teeth can increase the risk of being underweight.

Biatrial volume, estimated using magnetic resonance imaging, predicts atrial fibrillation recurrence after ablation.

INTRODUCTION: The predictive value of left atrial volume (LAV) in atrial fibrillation (AF) is known, but the relationship of right atrial volume (RAV) and biatrial volume (BAV) with AF recurrence after pulmonary vein isolation (PVI) is not clear. Cardiac magnetic resonance (CMR) imaging allows us to more precisely quantify atrial volume. We investigated LAV, RAV, and BAV as predictors of AF recurrence following PVI in AF patients. METHODS AND RESULTS: We assessed 100 AF patients (age = 59.8 ± 9.5 years, 74 males, 26 females) who underwent nonenhanced CMR before their first PVI. LAV and RAV were measured using CMR. All patients were in sinus rhythm during CMR. BAV was calculated as the sum of LAV and RAV. During the 8-month follow-up, AF recurrence occurred in 23 patients. LAV, RAV, and BAV were significantly greater in patients with AF recurrence than in those without (LAV, 103.7 ± 25.8 vs 81.8 ± 24.2 mL, P < 0.001; RAV, 109.4 ± 27.0 vs 82.2 ± 19.6 mL, P < 0.001; BAV, 213.1 ± 46.7 vs 164.1 ± 38.7 mL, P < 0.001). Multivariate logistic regression analysis revealed that increased LAV, RAV, and BAV were significantly correlated with AF recurrence. The area under the receiver operation characteristic curve for BAV showed the largest value compared to that of LAV or RAV alone. CONCLUSIONS: LAV, RAV, and BAV were independent predictors of AF recurrence after PVI. Quantifying BAV may additionally improve prognostic stratification compared with LAV or RAV.

Ventricular wall stress and silent myocardial damage are associated with pulse pressure in the general population.

Pulse pressure (PP) is a risk factor for cardiovascular diseases and is associated with increased afterload and myocardial oxygen demand. Brain natriuretic peptide (BNP) and heart-type fatty acid-binding protein (H-FABP) are known as biomarkers indicating ventricular wall stress and silent myocardial damage. However, the association between PP and ventricular wall stress and silent myocardial damage in the general population is unclear. The authors enrolled 3504 patients who participated in a community-based annual health check. Serum levels of BNP and H-FABP were measured as markers of ventricular wall stress and silent myocardial damage. Patients were divided into four groups according to the quartiles of PP. Patients in the highest PP group showed higher serum BNP and H-FABP levels than that of the other groups. Multivariate logistic analysis showed that high PP was independently associated with ventricular wall stress and silent myocardial damage on the basis of BNP and H-FABP levels. Compared with systolic blood pressure, diastolic blood pressure, and mean blood pressure, PP was superior in predicting ventricular wall stress and silent myocardial damage evaluated according to BNP and H-FABP levels, which was reflected by the receiver operating characteristic analysis. Screening of healthy patients revealed that high PP was related to high BNP and H-FABP levels, suggesting that an asymptomatic general population with high PP may be exposed to ventricular wall stress and myocardial damage and might be susceptible to silent heart failure.

Circulating Surfactant Protein-D Is Associated With Clinical Outcomes in Peripheral Artery Disease Patients Following Endovascular Therapy.

BACKGROUND: Peripheral artery disease (PAD) is a risk factor for the development of cardiovascular disease and death. Surfactant protein-D (SP-D) is a 43-kDa protein secreted from type II pneumocytes in the lungs. Recent studies have demonstrated that circulating SP-D plays a key role in the development of atherosclerosis and is related to clinical outcomes in patients with ischemic heart disease. However, it remains unclear whether circulating SP-D is associated with clinical outcomes in patients with PAD.Methods and Results:We enrolled 364 patients with PAD who underwent endovascular therapy. We measured serum levels of SP-D and Krebs von den Lungen-6 (KL-6). During a median follow-up period of 974 days, there were 69 major adverse cardiovascular and leg events (MACLE), including 48 major adverse cardiovascular events (MACE). Kaplan-Meier analysis demonstrated that patients with high SP-D (≥110 ng/mL) had higher rates of MACE and MACLE than those with low SP-D. Multivariate Cox proportional hazard regression analysis demonstrated that SP-D, but not KL-6, was an independent predictor of MACE and MACLE. The addition of SP-D to known risk factors significantly improved the C index and net reclassification index. The circulating SP-D level was affected by sex, diabetes mellitus, and cilostazol prescription. CONCLUSIONS: Circulating SP-D was associated with clinical outcomes in patients with PAD, suggesting that it may be a new therapeutic target in these patients.

The Association between Glomerular Filtration Rate Estimated Using Different Equations and Mortality in the Japanese Community-Based Population: The Yamagata (Takahata) Study.

BACKGROUND: To evaluate renal function, the indices of estimated glomerular filtration rate (eGFR) obtained using several equations, including the Japanese versions of the serum creatinine-based MDRD equation (eGFRcreat), Chronic Kidney Disease Epidemiology Collaboration equation (eGFR-EPI), and serum cystatin C-based equation (eGFRcys), are utilized. This study prospectively examined the association between these eGFR values and all-cause mortality during a 12-year observational period in a community-based population. METHODS AND RESULTS: The subjects of this study were 1312 participants undergoing a health checkup, aged ≥40 years. In the total population, the mean eGFR values (mL·min-1·1.73 m-2) were 81.5 for eGFRcreat, 78.1 for eGFR-EPI, and 76.6 for eGFRcys. There were 141 deaths during the observation period, and the area under the receiver operating characteristic curve for predicting mortality was 0.59 for eGFRcreat, 0.67 for eGFR-EPI, and 0.70 for eGFRcys (all P < 0.01). In the Cox proportional analysis adjusted for age and sex, eGFRcys, but not eGFRcreat and eGFR-EPI, showed a significant association with all-cause mortality (per 15 mL·min-1·1.73 m-2 decrease: hazard ratio 1.40, 95% confidence interval 1.18-1.67). CONCLUSIONS: This study revealed that eGFRcys showed lower values than eGFRcreat and eGFR-EPI and was significantly associated with all-cause mortality in the Japanese community-based population.

Impact of reduced forced expiratory volume on cardiac prognosis in patients with chronic heart failure.

In patients with chronic heart failure (CHF), comorbidity of airflow limitation is associated with poor outcomes. The forced expiratory volume in 1 s (FEV1) is used to evaluate the severity of airflow limitation. However, the impact of FEV1 severity on prognosis has only been partially elucidated in patients with CHF. In total, 248 consecutive patients with CHF who successfully fulfilled spirometric measurement criteria were enrolled and prospectively followed. Percent predicted FEV1 (FEV1%predicted) was associated with the New York Heart Association Functional Classification. FEV1%predicted was significantly associated with diastolic dysfunction, evaluated using echocardiography; elevated inflammation markers; and increased pulmonary arterial pressure. There were 60 cardiac events, including 9 cardiac-related deaths and 51 re-hospitalizations due to the exacerbation of CHF during a follow-up period. Kaplan-Meier analysis revealed that the lowest FEV1%predicted group had the highest event rate, irrespective of the presence of smoking history. Multivariate Cox proportional hazard analysis showed that FEV1%predicted was an independent predictor of cardiac events after adjusting for confounders. The net reclassification improvement and integrated discrimination improvement were improved by the addition of FEV1%predicted to other cardiac risk factors. Decreased FEV1%predicted was independently associated with the poor cardiac outcomes in patients with CHF.

Impact of cigarette smoking on decline in forced expiratory volume in 1s relative to severity of airflow obstruction in a Japanese general population: The Yamagata-Takahata study.

BACKGROUND: Few studies are available regarding the annual decline of forced expiratory volume in 1s (FEV1) in chronic obstructive pulmonary disease patients with mild airflow obstruction. This study sought to clarify to what extent cigarette-smoking individuals with mild airflow obstruction lose pulmonary function annually. METHODS: From 2004 to 2006, pulmonary function tests were performed on people >40 years of age, during the annual health checkup held in Takahata, Yamagata, Japan (initial study population, n=3253). In 2011, pulmonary function tests were performed again on participants who agreed to undergo reexamination (follow-up study population, n=838). RESULTS: Smokers have decreased pulmonary function in terms of percent forced vital capacity (FVC), %FEV1, and FEV1/FVC; the stages of airflow obstruction were also more severe in smokers than never-smokers. The annual decline in FEV1 was significantly greater in smokers than in never-smokers. The median annual decline in FEV1 was most significant in individuals with mild airflow obstruction. The annual decline in FEV1 was greater in smokers with mild airflow obstruction than in smokers with moderate airflow obstruction. In analyzing the decline in %FEV1, the annual change in smokers with mild airflow obstruction was greater than that in smokers with normal spirometric values. CONCLUSION: The annual decline in FEV1 was most significant in smokers with mild airflow obstruction in a Japanese general population. This highlights the importance of early detection of chronic obstructive pulmonary disease patients among the general population in order to prevent disease progression in undiagnosed patients.

The Association between Serum Uric Acid and Renal Damage: The Takahata Study - New Insights.

BACKGROUND: Hyperuricemia is a risk factor for causing end-stage kidney disease and cardiovascular disease in the general population; however, several aspects, such as the site of kidney damaged by hyperuricemia and the threshold levels of serum uric acid for the development of renal damage, have not been fully clarified. SUMMARY: To examine these aspects, we analyzed data from the Takahata study, a community-based cohort study involving participants of an annual health check-up, and used urinary albumin creatinine ratio (UACR) and urinary ß2-microglobulin creatinine ratio (UBCR) in spot urine as indices of glomerular and tubular damage respectively. In cross-sectional analysis, increased serum uric acid levels were accompanied by higher UACR values and lower UBCR values. Multivariate analysis revealed that albuminuria (UACR ≥30 mg/g), but not elevated UBCR, was independently associated with increased uric acid (≥7 mg/dL for males, ≥6 mg/dL for females). In longitudinal analysis, uric acid at baseline was an independent factor for a 1-year increase in the UACR. Cox-proportional hazard model analysis with adjustment for possible confounders including age, renal function, and comorbidities revealed that hyperuricemia was an independent risk factor for all-cause and cardiovascular mortality in females. Key Messages: Our results revealed that elevated uric acid is an independent risk factor for glomerular damage, but not tubular damage, and that the risk for renal damage and mortality might be increased at the high-normal range of uric acid in the community-based population.

Prevalence of diabetes mellitus in individuals with airflow obstruction in a Japanese general population: The Yamagata-Takahata Study.

BACKGROUND: Diabetes has been reported as a comorbidity of chronic obstructive pulmonary disease (COPD) in Western countries, but it has not been demonstrated in epidemiological reports in Japan. The purpose of this study was to clarify whether the relationship between airflow obstruction and diabetes can be confirmed in a Japanese general population. METHODS: From 2004 to 2006, blood sampling and pulmonary function tests were performed on 3045 people over the age of 40 years in annual health check-ups held in Takahata, Yamagata Prefecture, Japan. Pulmonary function was re-evaluated in 2009 and 2011. RESULTS: The prevalence of diabetes did not differ between subjects with and without airflow obstruction. Furthermore, although body mass index decreased, no increase in the prevalence of diabetes was observed with the progression of airflow obstruction. The annual changes in forced expiration volume in 1s (FEV1) did not differ depending on the presence or absence of diabetes in the study population. CONCLUSION: There was no difference in the prevalence of diabetes between subjects with airflow obstruction and those without. As patients with COPD in Japan are thinner than in the West, diabetes may not be a common comorbidity in Japanese patients with COPD.

Sex differences in impact of coronary artery calcification to predict coronary artery disease.

OBJECTIVE: To assess sex-specific differences regarding use of conventional risks and coronary artery calcification (CAC) to detect coronary artery disease (CAD) using coronary CT angiography (CCTA). METHODS: The Nationwide Gender-specific Atherosclerosis Determinants Estimation and Ischemic Cardiovascular Disease Prospective Cohort study is a prospective, multicentre, nationwide cohort study. Candidates with suspected CAD aged 50-74 years enrolled from 2008 to 2012. The outcome was obstructive CAD defined as any stenosis ≥50% by CCTA. We constructed logistic regression models for obstructive CAD adjusted for conventional risks (clinical model) and CAC score. Improvement in discrimination beyond risks was assessed by C-statistic; net reclassification index (NRI) for CAD probability of low (<30%), intermediate (30%-60%) and high (≥60%); and risk stratification capacity. RESULTS: Among 991 patients (456 women, 535 men; 65.2 vs 64.4 years old), women had lower CAC scores (median, 4 vs 60) and lower CAD prevalence (21.7% vs 37.0%) than men. CAC significantly improved model discrimination compared with clinical model in both sexes (0.66-0.79 in women vs 0.61-0.83 in men). The NRI for women was 0.33, which was much lower than that for men (0.71). Adding CAC to clinical model had a larger benefit in terms of moving an additional 43.3% of men to the most determinant categories (high or low risk) compared with -1.4% of women. CONCLUSIONS: The addition of CAC to a prediction model based on conventional variables significantly improved the classification of risk in suspected patients with CAD, with sex differences influencing the predictive ability. TRIAL REGISTRATION NUMBER: UMIN-CTR Clinical Trial: UMIN000001577.

Presence of Myocardial Damage Predicts Future Development of Hypertension in a Normotensive Japanese General Population: The Yamagata (Takahata) Study.

BACKGROUND: A modest rise in blood pressure (BP) reportedly increases cardiovascular mortality despite not reaching obvious hypertension, suggesting that target organ damages are latently induced by slight BP rising. The goal of this study was to determine whether presence of subclinical myocardial damage can predict the future development of hypertension in the normotensive general population. METHODS AND RESULTS: The cohort study was conducted with subjects who participated in a community-based annual health check. Normotensive subjects without prior cardiovascular diseases at baseline were eligible for analyses (n = 524, mean age 58 ± 9 years; 53% women). We measured heart-type fatty acid binding protein (H-FABP) at baseline as a biomarker of ongoing myocardial damage. Longitudinal changes in BP were examined during median follow-up period of 6.2 years, and we investigated the association between the baseline H-FABP level and longitudinal BP changes. RESULTS: During the follow-up, 177 subjects (34%) developed hypertension. In multivariate Cox proportional hazard analysis adjusted for potential confounders including age and baseline BP, presence of myocardial damage was significantly associated with the development of hypertension (hazard ratio 1.80, 95% confidence interval, 1.26-2.54; P = 0.0014). Furthermore, relative risk of myocardial damage for incident hypertension was higher in younger subjects and lower BP category. CONCLUSIONS: Presence of subclinical myocardial damage was independently associated with the future development of hypertension in the normotensive general population.

The impact of non-alcoholic fatty liver disease fibrosis score on cardiac prognosis in patients with chronic heart failure.

Liver abnormalities have a strong impact on clinical outcomes in patients with heart failure (HF), and are known as cardio-hepatic syndrome. The non-alcoholic fatty liver disease (NAFLD) fibrosis score (NFS) has been developed to identify liver fibrosis in patients with NAFLD. It remains to be determined whether NFS is associated with cardiovascular prognosis in patients with chronic heart failure (CHF). We calculated NFS in 516 patients with CHF admitted to our hospital. The clinical endpoints were deaths due to progressive HF, myocardial infarction, stroke, and sudden cardiac death, and rehospitalization for worsening HF. There were 173 cardiovascular events noted during a median follow-up of 464 days. Patients with cardiovascular events showed a higher NFS as compared with those without. We divided the patients into four groups according to quartiles of NFS. The proportion of New York Heart Association functional class III/IV and serum brain natriuretic peptide levels were increased with increasing NFS. Kaplan-Meier analysis revealed that cardiovascular event rate was increased with increasing NFS in patients with CHF. In multivariate Cox proportional hazards analysis, NFS was independently associated with cardiovascular events after adjustment for confounding factors. Elevated NFS was associated with unfavorable outcomes in patients with CHF. Liver fibrosis assessed by NFS may provide valuable prognostic information in patients with CHF.