Elevated Aminotransferase Levels and Intracerebral Hemorrhage Deaths in a General Japanese Population.

Although chronic liver disease has been associated with cardiovascular disease, to which metabolic syndrome might be related, intracerebral hemorrhage (ICH) generally has not been focused. Associations of chronic liver disease assessed by aspartate (AST) and alanine (ALT) aminotransferase levels with ICH deaths were examined using 15,952 subjects without a history of cardiovascular disease who underwent annual health checkups in 1997 in Japan. Proportional hazards regression analyses adjusted for age, sex, hypertension, current smoking, diabetes mellitus, drinking habits, excess body weight, and hypercholesterolemia were performed. During a mean follow-up of 18.6 ± 7.2 years, there were 227 stroke deaths (including 124 ischemic and 60 ICH deaths) and 135 coronary deaths. Elevated aminotransferase levels, defined as a serum AST or ALT level of ≥ 30 IU/L were significantly associated with ICH deaths (hazard ratio (HR) = 2.72, 95% confidence interval (CI) = 1.56-4.73, P = 0.0004). Because elevated aminotransferase levels are frequently observed in alcoholic or metabolic liver diseases, additional analyses were performed to examine the effect of drinking habits and/or metabolic syndrome on the association of elevated aminotransferase levels with ICH deaths. After exclusion of subjects with any drinking habit (n = 9,941), elevated aminotransferase levels were significantly associated with ICH deaths (HR = 2.88, 95%CI = 1.44-5.76, P = 0.0028). After exclusion of subjects with at least one metabolic syndrome component (n = 5,672), elevated aminotransferase levels were significantly associated with ICH deaths (HR = 6.47, 95% CI = 1.85-22.6, P = 0.0035). Elevated aminotransferase levels were not associated with ischemic stroke or coronary deaths in any models. Elevated aminotransferase levels were significantly associated with ICH deaths, independent of drinking habits, or metabolic syndrome.

Increased Incidence of ECG Abnormalities in the General Population During the COVID-19 Pandemic.

To examine the effect of the COVID-19 pandemic on the cardiovascular system in the general population, we compared ECG changes after the onset of the COVID-19 pandemic with those before the pandemic period. The incidence of newly appeared ECG abnormalities (T wave abnormalities, ST-segment depression including minor changes, and abnormal Q waves) from 2019 to 2020 (COVID-19 period) was compared with that from 2018 to 2019 (control period) in subjects 40 to 74 years of age without a history of cardiovascular disease who had 12-lead ECG recordings during annual health checkups offered to adult citizens of Moriguchi City, Osaka, Japan. Logistic regression analyses were performed after adjusting for cardiovascular risk factors. There were 5,221 eligible subjects in the control period and 4,100 eligible subjects in the COVID-19 period. The incidences of newly appeared ECG abnormalities were 5.2% for T wave abnormalities, 2.8% for ST-segment depression, and 1.1% for abnormal Q waves in the control period, whereas they were 5.8%, 4.3%, and 1.7% respectively, in the COVID-19 period. The incidence of ST-segment depression (odds ratio (OR) = 1.59, 95% confidence interval (CI) = 1.27-1.98, P < 0.0001) and that of abnormal Q waves (OR = 1.56, 95%CI = 1.09-2.22, P = 0.0149) in the COVID-19 period were significantly higher compared to those of the control period. In conclusion, increased incidences of newly appeared ST-segment depression and abnormal Q waves were observed during the COVID-19 pandemic period.

[Effect of the national lifestyle modification project conducted in Japan on the parameters of metabolic syndrome].

OBJECTIVES: Although the national lifestyle modification project targeting metabolic syndrome in the general population conducted by the Japanese government started in 2008, the project's long-term effects have not yet been evaluated. Associations of taking the project's lifestyle modification guidance with improvement of parameters related to metabolic syndrome after 1, 2, 3, and 4 years were assessed in participants who met the metabolic syndrome criteria for the guidance. METHODS: While improvement was defined when the parameters had met the criteria for metabolic syndrome at the initial checkup but did not at the time of evaluation without medication, deterioration was defined when they had not met the criteria at the initial checkup but, at the time of evaluation, they did or the subjects received the medication. Logistic regression analyses were used to evaluate improvement by the guidance adjusted for age, sex, systolic blood pressure, HDL cholesterol level, and hemoglobin (Hb)A1c level at baseline. RESULTS: From 2008 to 2011, 3742 participants (mean age 61±10 years, men 62%) met the criteria for the lifestyle modification guidance. Numbers of participants eligible for evaluation were 2690, 1894, 1330, and 779 at 1, 2, 3, and 4 years after the initial checkup, respectively. Based on the multivariate logistic regression analyses, receiving the guidance was significantly associated with improvement of body mass index (BMI) (odds ratio (OR)=1.66, 95% confidence interval (CI)=1.17-2.37), waist (OR=1.77, 95%CI=1.35-2.31), and HbA1c (OR=1.82, 95%CI=1.05-3.13) at the 1-year evaluation; improvement of BMI (OR=1.51, 95%CI=1.01-2.26) and waist (OR=1.61, 95%CI=1.18-2.20) at the 2-year evaluation; and improvement of waist (OR=1.67, 95%CI=1.12-2.48) at the 3-year evaluation. However, BMI, waist, and HbA1c at other evaluations including the 4-year evaluation and the remaining parameters at any evaluations were not significantly improved by the guidance. In addition, receiving the guidance was significantly associated with deterioration of HbA1c at the 4-year evaluation (OR=2.49, 95%CI=1.18-5.24). CONCLUSION: Although HbA1c at the 1-year evaluation and parameters related to overweight were improved at the 1-, 2-, and 3-year evaluations, no parameters of metabolic syndrome were significantly improved by the guidance at the 4-year evaluation.

Prognosis of subjects with Brugada-type electrocardiogram in a population of middle-aged Japanese diagnosed during a health examination.

There is controversy about the clinical significance of an incidental finding of a Brugada-type electrocardiogram (ECG) pattern. To assess the prognosis of subjects with a diagnosis of a Brugada-type ECG pattern during a health examination, 13,904 subjects (mean age 58 +/- 10 years) who had the annual health examination including an ECG offered to adult citizens of Moriguchi City, Osaka, Japan, in 1997 were studied. A Brugada-type ECG pattern was found in 98 subjects, and 37 subjects had type 1. During a mean follow-up of 7.8 +/- 1.6 years, there were 4 deaths (4.1%) and 1 cardiovascular death (1.0%) in subjects with a Brugada-type ECG pattern, whereas there were 612 deaths (4.4%) and 142 cardiovascular deaths (1.0%) in those without. One cardiovascular death in a subject with a Brugada-type ECG pattern was sudden death. Unadjusted proportional hazards regression analyses showed that Brugada-type ECG pattern was not associated with either all-cause (hazard ratio [HR] 0.90, 95% confidence interval [CI] 0.34 to 2.41) or cardiovascular mortality (HR 0.97, 95% CI 0.14 to 6.93). After adjustment for cardiovascular risk factors, Brugada-type ECG pattern had no association with either all-cause (HR 0.77, 95% CI 0.29 to 2.07) or cardiovascular mortality (HR 1.01, 95% CI 0.14 to 7.31). In conclusion, Brugada-type ECG patterns diagnosed during a health examination in a middle-aged population had a low risk of sudden death and were not associated with increased risk of either cardiovascular or all-cause mortality.

Effect of beta-blockers on the mortality of Japanese patients with myocardial infarction.

BACKGROUND: After a myocardial infarction, a higher prevalence of coronary vasospastic response has been reported in the Japanese population than in the Caucasian population. Beta-blockers may exacerbate coronary vasospasm. However, beta-blockers are given to Japanese patients after an acute myocardial infarction, though the mortality benefit is unknown. Thus, we investigated the mortality benefit of beta-blockers given to Japanese patients after an acute myocardial infarction. METHODS: We prospectively studied consecutive patients with a first myocardial infarction admitted to the coronary care unit of Kansai Medical University Hospital, Osaka, Japan from May 1994 through the end of 2001. Patients who died during hospitalization or who were referred for coronary artery bypass graft surgery were excluded. The association of beta-blocker use with mortality after discharge was assessed by a proportional hazards regression analysis. RESULTS: There were 546 patients and 400 (73.3%) patients were treated with beta-blockers at the time of discharge from hospital. During a mean follow-up of 2 years, 46 (8.4%) patients died. Beta-blocker therapy was associated with a reduced mortality after adjustment for age, gender, Q wave myocardial infarction, reperfusion therapy during acute phase, Killip functional class, serum creatinine level, cardiovascular risk factors, and medications (hazard ratio=0.51, 95% confidence interval=0.27 to 0.95). CONCLUSIONS: Contrary to the concern that beta-blocker therapy might induce coronary vasospasm and reduce survival, beta-blocker therapy improved survival after discharge in Japanese patients with a first myocardial infarction.

Haemoglobin level influences plasma brain natriuretic peptide concentration.

OBJECTIVE: It has been demonstrated that the haemoglobin (Hb) level is associated with the prognosis of congestive heart failure (CHF). Correction of anaemia has improved CHF outcomes even in patients without anaemia. Lower Hb level may play a more important role in left ventricular (LV) dysfunction than previously recognized. This study aimed to evaluate the association of Hb level with plasma brain natriuretic peptide (BNP) level as a marker of LV function adjusted for known determinants of BNP. METHODS AND RESULTS: Association of Hb level with plasma BNP level was studied in 279 outpatients of cardiology (mean age 61 +/- 16, 54% men) using multivariate regression analysis. Mean Hb level was 13.7 +/- 1.5 g/dl and 14% of patients had anaemia. Median BNP level was 28 pg/ml (range < 4 to 580 pg/ml). In total subjects, the multivariate model adjusted for age, sex, history of CHF, atrial fibrillation, serum creatinine level, LV wall motion abnormality, end-diastolic LV dimension, LV mass index, and cardiovascular risk factors showed that a lower Hb level was significantly associated with higher BNP level (p = 0.0243). In "normal" subjects who did not have a history of CHF, atrial fibrillation, LV wall motion abnormality, LV dilatation, valvular abnormality, or LV hypertrophy, a lower Hb level was significantly associated with a higher BNP level (p = 0.0012) after adjustment for age, sex, serum creatinine level, and cardiovascular risk factors. CONCLUSIONS: Lower Hb levels are associated with higher plasma BNP levels independent of age, sex, serum creatinine level, LV wall motion abnormality, LV hypertrophy, history of CHF, atrial fibrillation, and cardiovascular risk factors.

Is baseline autonomic tone associated with new onset atrial fibrillation?: Insights from the framingham heart study.

BACKGROUND: Recent reports have indicated that autonomic tone fluctuations measured by heart rate variability (HRV) precede episodes of paroxysmal atrial fibrillation (AF). Little is known about the impact of baseline autonomic tone and the development of new onset AF in a population-based cohort. The purpose of this study was to assess the role of HRV as a predictor of new onset AF. METHOD: Ambulatory ECG recordings obtained from the Framingham Heart Study subjects attending a routine examination were processed for HRV. The HRV variables analyzed included standard deviation of normal R-R intervals (SDNN), low frequency power (LF), high frequency power (HF), and LF/HF ratio. There were 1434 women and 1142 men (54 +/- 14.1 years) eligible for the study. RESULTS: In 12 years of follow-up, 65 women and 67 men had new onset AF. The study had 80% power to detect a hazard ratio (HR) of 1.3 per standard deviation (SD) decrement in HRV. A one SD decrement in log LF/HF was associated with increased risk of developing AF (HR = 1.23; 95% confidence intervals (CI) = 1.06-1.44) in age- and sex-adjusted models; the association was no longer significant (HR = 1.15; 95% CI = 0.98-1.35) after adjusting for potential confounders. CONCLUSION: Autonomic dysregulation at baseline, as reflected by an altered HRV is associated with risk of AF; however, this association does not persist after adjusting for potential confounders. Much of the apparent association between HRV and AF is mediated by traditional risk factors.

Usefulness of plasma brain natriuretic peptide levels in predicting dobutamine-induced myocardial ischemia.

Plasma brain natriuretic peptide (BNP) levels have been associated with left ventricular dysfunction and acute myocardial infarction. Although natriuretic peptide responses have been linked to exercise-induced myocardial ischemia, it is not known whether BNP levels predict dobutamine-induced myocardial ischemia. The aim of this study was to determine whether elevations in BNP levels immediately before or after dobutamine-induced stress are associated with echocardiographic myocardial ischemia. Plasma BNP was measured before and after stress during dobutamine-stress echocardiography in 317 patients (aged 68 +/- 11 years; 46% women) who had creatinine <1.5 mg/dl and did not have valvular disease. Ischemia, as assessed by blinded echocardiographic interpretation, was noted in 31 patients (10%). In univariable analyses, prestress BNP was predictive of echocardiographic ischemia (rates of ischemia according to tertiles of BNP 4%, 9%, and 16%, chi-square for trend = 8, p = 0.0059). The change in BNP levels with dobutamine stress was not associated with ischemia. In multivariable analyses, after adjusting for age, gender, and left ventricular ejection fraction, BNP before and after stress remained predictive of ischemia (1 SD increase in the log of resting BNP adjusted odds ratio 2.0, 95% confidence interval 1.3 to 3.0, p = 0.002). In this pilot study, resting BNP was predictive of dobutamine-induced ischemia. Future work is needed to confirm these findings.

Genome scan linkage results for heart rate variability (the Framingham Heart Study).

There is a substantial heritable component to the beat-to-beat variation in heart rate. However, the molecular mechanisms underlying the control of heart rate variability (HRV) remain unknown. The present study sought to identify chromosomal regions linked to HRV phenotypes. The first 2 hours of ambulatory electrocardiographic recordings obtained from Framingham Heart Study subjects attending a routine examination were processed for HRV. HRV variables analyzed included very-low-frequency power, low-frequency power, and high-frequency power. Gender-specific residuals were used for log-transformed HRV data after adjustment for age, HR, systolic and diastolic blood pressures, and coffee and alcohol consumption. In conjunction with a 10-cM genome-wide scan, HRV data were available for 725 subjects in 230 extended families, including 390 sibling pairs. Variance component log-of-the-odds (LOD) scores were obtained. The highest multipoint LOD scores were obtained for log very-low frequency on chromosome 15 at 62 cM (LOD 1.84) and for log low frequency on chromosome 2 at 153 cM (LOD 1.81). These data suggest there may be influential genetic regions contributing to HRV. Further studies are warranted to identify genes in these regions that may influence autonomic tone. Recognition of the genetic determinants of HRV may provide additional insights into the pathophysiology of the autonomic nervous system and offer clues to its modulation.