Age-specific incidence rates of atrial fibrillation and risk factors for the future development of atrial fibrillation in the Japanese general population

BackgroundAge-specific incidence rates of atrial fibrillation (AF) and risk factors for the development of AF have not been sufficiently determined in Japan.MethodsA total of 130,396 community dwellers in Iwate Prefecture who did not have AF as assessed by an electrocardiogram at the 2010 annual health check-up were enrolled. We checked cases of newly developed AF in the following 3-year check-ups (in 2011, 2012, and 2013). Age-specific incidence rates (in subjects aged 45?54, 55?64, 65?74, 75?84, and 85 years or older) of AF were determined in both sexes, and multivariate-adjusted logistic regression analysis was performed using incident AF as an independent variable and already known risk factors at the 2010 survey as explanatory variables.ResultsAge-specific incidence rates (per 1000 person-years) of AF in subjects aged 45?54, 55?64, 65?74, 75?84, and 85 years or older were 1.42, 3.84, 6.73, 8.53, and 14.13, respectively, in males and 0.12, 0.53, 2.15, 3.40, and 10.48, respectively, in females. Odds ratios for incident AF and their 95% confidence intervals were 1.20 (1.01–1.43) in subjects with hypertension, 1.55 (1.30–1.85) in overweight subjects, 1.79 (1.23–2.61) in subjects with coronary artery disease, and 1.29 (1.08–1.53) in subjects who drank every day among male subjects and they were 1.70 (1.19–2.45) in subjects with hypertension and 1.64 (1.17–2.30) in overweight subjects among female subjects.ConclusionsAge-specific incidence rates of AF in Iwate were determined. The results showed age, hypertension, obesity, coronary artery disease, and regular drinking habit significantly increased the risk of future development of AF.     

Long-chain n-3 polyunsaturated fatty acids intake and cardiovascular disease mortality risk in Japanese: A 24-year follow-up of NIPPON DATA80

BackgroundDietary intake of long-chain n-3 PUFA (LCn3FA) among Japanese is generally higher than that in Western populations. However, little is known whether an inverse association of LCn3FA with cardiovascular disease (CVD) risk exists in a population with higher LCn3FA intake.ObjectiveTo investigate the association between LCn3FA intake and the long-term risk of CVDs in a Japanese general population.MethodsWe followed-up a total of 9190 individuals (56.2% women, mean age 50.0 years) randomly selected from 300 areas across Japan and free from CVDs at baseline. Dietary LCn3FA intake was estimated using household weighed food records. Cox models were used to calculate multivariate-adjusted hazard ratios (HR) and confidence intervals (CI) according to sex specific quartiles of LCn3FA intake.ResultsDuring 24-year follow-up (192,897 person-years), 879 cardiovascular deaths were observed. The median daily intake of LCn3FA was 0.37% kcal (0.86 g/day). Adjusted HR for CVD mortality was lower in the highest quartile of LCn3FA intake (HR 0.80; 95% CI 0.66–0.96) compared with the lowest quartile, and the trend was statistically significant (P = 0.038). The similar but statistically non-significant trends were observed for coronary heart disease death and stroke death. In analyses by age groups, the inverse associations of LCn3FA intake with the risk of total CVD death and stroke death were significant in younger individuals (30–59 years at baseline).ConclusionLCn3FA intake was inversely and independently associated the long-term risk of total CVD mortality in a representative sample of Japanese with high LCn3FA intake.     

Stroke risk in an elderly population with atrial fibrillation

Patients with nonvalvular atrial fibrillation (AF) have an increased risk of stroke, but the absolute rate of stroke varies widely depending on coexistent vascular disease. We assessed the stroke rate and predictive value of two published schemes for stroke risk stratification in a population-derived cohort of 259 elderly people with nonvalvular AF followed for a median of 5.3 years. The rate of ischemic stroke was 2.8% per year (95% confidence interval [CI] 1.9, 3.9). Thirty-one percent were predicted to be at low risk, and their stroke rate was 1.7% per year (95% CI 0.6, 3.8). Many people with AF in this population-derived cohort had relatively low rates of stroke. Further studies to reliably stratify stroke risk in patients with AF are needed.     

Combined cardiovascular risk factors and outcome: NIPPON DATA80, 1980-1994.

BACKGROUND: To examine the prognostic significance of the high-risk group with combined cardiovascular risk factors in the Japanese, we analyzed the relationship between the high-risk group with combined risks and coronary heart disease (CHD) and stroke mortality using the NIPPON DATA80 database. METHODS AND RESULTS: At baseline in 1980, those of age>or=30 years were randomly selected and 4,144 men and 5,318 women without CHD and/or stroke at baseline were followed for 14 years. The cutoff values for risk components obtained heuristically by Cox analysis were hypertension (systolic>or=130, or diastolic>or=85 mmHg, or on antihypertensive drugs), hypercholesterolemia (total cholesterol>or=200 mg/dl), hyperglycemia (>or=130 mg/dl, or self-reported diabetes) and obesity (body mass index>or=27 kg/m2). Subjects were divided into 3 groups (0, 1-2 and 3-4 risks). Compared with those men in the risk 0 group, the hazard ratios in men in the risk 3-4 for CHD mortality was 8.04 (95% confidence interval: 1.03-62.6), and the stroke mortality was 5.06 (1.53-16.7). In women, no statistically significant difference was found due to a lesser number of events. CONCLUSION: The high-risk group with combined risk factors is important risk for Japanese men.     

Association of proteinuria with incident atrial fibrillation in the general Japanese population

BackgroundAlthough proteinuria has been associated with incident atrial fibrillation (AF) in Western countries, the association has not been investigated in the general Japanese population.MethodsParticipants aged ≥40 years who underwent the Japanese specific health check-up in Kanazawa City in 2013 and who completed a urine dipstick test were included in this study. Exposure was considered as presence or absence of proteinuria (≥1+). The outcome was incident AF confirmed by 12-lead electrocardiography. The Cox proportional hazard model was used to compute hazard ratio (HR) of proteinuria (≥1+) for incident AF after adjustment for traditional risk factors. We also completed stratified analyses by baseline characteristics.ResultsA total of 37,910 participants aged ≥40 years were included (mean age: 72.3 years, male sex: 37%). Proteinuria ≥1+ was observed in 2.765 (7.3%) participants. During a median follow-up period of 5 years, 708 incident AF cases were observed. Proteinuria ≥1+ was associated with incident AF (HR, 1.47: 95% confidence interval, 1.18–1.84) after covariate adjustment. Stratified analysis demonstrated that the association of proteinuria with AF was stronger in participants <75 years [HR 1.89 (95% CI 1.32–2.70)] compared with those ≥75 years [HR 1.27 (95% CI 0.95–1.69)] (interaction p-value = 0.02).ConclusionsProteinuria was significantly associated with incident AF in the general Japanese population. The evaluation of proteinuria using urine dipstick test may be useful in the evaluation of incident AF, especially in younger general population.     

The proportion of individuals with alcohol-induced hypertension among total hypertensives in a general Japanese population: NIPPON DATA90.

Japanese men consume more alcoholic beverages than men in many other developed countries. The high consumption rate of alcoholic beverages among Japanese men may contribute to the high prevalence of hypertension in Japan. In the present study, we calculated the odds ratio for hypertension in alcohol drinkers based on recent criteria using data from a nationwide survey conducted in Japan in 1990, and estimated, among total hypertensives in a general Japanese population, the percentage of hypertensives whose condition was due to alcohol consumption. Of 3,454 male participants, 64.8% were drinkers (1 gou/day, 28.9%; 2 gou/day, 20.1%; 3 gou/day or more, 8.7%; ex-drinkers, 7.0%) and 49.8% were hypertensive, whereas 7.6% of 4,808 female participants were drinkers (1 gou/day, 5.2%; 2 gou/day or more, 1.3%; ex-drinkers, 1.1%) and 43.1% were hypertensive (1 gou=23.0 g of alcohol). In both sexes, drinkers had a higher odds ratio for hypertension than never drinkers, and there was a significant dose-response relationship between the amount of alcohol consumed and the odds ratio for hypertension. Among all hypertensives, the percentage whose hypertension was due to alcohol consumption was 34.5% (95% confidence interval, 10.9%-51.9%) for men and 2.6% (0.8%-5.8%) for women. The corresponding proportion based on daily alcohol intake was 12.7% for 1 gou/day, 11.1% for 2 gou/day, 5.8% for 3 gou/day or more, and 4.8% for ex-drinkers in men, and 1.8% for 1 gou/day, 0.7% for 2 gou/day or more, and -0.1% for ex-drinkers in women. In conclusion, we found that a large percentage of the hypertensives in a general Japanese male population had alcohol-induced hypertension.     

Hospitalizations for atrial fibrillation in the general male population: morbidity and risk factors

OBJECTIVES: To analyse the incidence, prevalence, aetiology, risk factors and prognosis of hospitalizations for atrial fibrillation. SUBJECTS: A random population sample of 7495 men aged 47-55 years was first examined in 1970-73. During follow-up until 1996 (mean 25.2 years) 754 men were hospitalized with a diagnosis of atrial fibrillation. RESULTS: In the age groups of 55-64, 65-74 and 75-79 years, the incidence rate was 2.0, 5.8 and 17.3 per 1000 person years, and the prevalence 1.2, 4.2 and 8.0%, respectively. Definite or possible coronary heart disease was diagnosed in 46.0%, heart failure in further 20.2% and valvular heart disease or cardiomyopathy in 4.5%. In bivariate analysis adjusted for age, the following factors were significantly associated with future hospitalization for fibrillation: a family history of myocardial infarction, stroke in mother, dyspnoea at entry, alcohol abuse, high body stature and body weight, high blood pressure but not diabetes, high serum cholesterol, high heart rate, smoking, coffee consumption or psychological stress. Significant risk factors in multivariate analysis were age, odds ratio (OR) [95% confidence interval (CI)] -1.11 (1.07, 1.16) per year, hospitalization for coronary heart disease or heart failure -6.77 (5.17, 8.87), stroke in mother - 1.49 (1.15, 1.93), high body stature -1.04 (1.03, 1.06) per cm, high body mass index (BMI) -1.07 (1.04, 1.10) per kg m(-2), as well as hypertension -1.33 (1.07, 1.65). After a diagnosis of atrial fibrillation, mortality was increased by 3.3 times. CONCLUSION: In spite of a clinical association with coronary heart disease, risk factors for atrial fibrillation were only partly the same. Prevention includes avoidance of weight gain and control of blood pressure as well as prevention of myocardial infarction and heart failure.     

Effect of conventional risk factors for excess cardiovascular death in men: NIPPON DATA80.

BACKGROUND: The present study examined how sex differences in conventional risk factors for cardiovascular disease (CVD), especially smoking, account for excess male mortality from CVD in Japan. METHODS AND RESULTS: In a 14-year follow-up study, causes of death were ascertained among 10,546 Japanese aged 30 years or older at the baseline. The proportion of the excess male risk of CVD explained by the differences in risk factors was estimated as (HR0-HR1)/(HR0-1), where HR0 is the age-adjusted hazard ratio (men vs women) and HR1 is the age and risk factor-adjusted hazard ratio. The age-adjusted male:female ratios were 1.60 (95% confidence interval (CI), 1.32-1.94) for CVD, 1.75 (95% CI, 1.33-2.30) for stroke, and 1.55 (95% CI, 0.97-2.49) for coronary heart disease. The proportion of excess male risk of CVD explained by smoking was 46% and excess risk explained by all risk factors including smoking was 36%. In men, drinking habits decreased the excess risk of CVD. Except for the association between drinking habits and CVD, the impact of the hazard ratios of conventional risk factors had no sex difference. CONCLUSIONS: Smoking contributes substantially to excess male mortality from CVD when the smoking rates vary substantially by sex.     

Electrocardiogram screening for left high R-wave predicts cardiovascular death in a Japanese community-based population: NIPPON DATA90.

Little is known about the efficacy of left ventricular hypertrophy diagnosed by electrocardiography for predicting cardiovascular disease in a general Japanese population. In a large cohort of participants selected randomly from the overall Japanese population, we attempted to evaluate the usefulness of a high amplitude R-wave (left high R-wave) on the electrocardiogram for predicting cardiovascular death. A total of 6,688 Japanese (mean age, 50.7 years old; 57% women) free of previous cardiovascular disease and use of antihypertensive agents at baseline were followed for 10 years, from 1990 to 2000. Left high R-wave on the electrocardiogram (the Minnesota Code, 3-1 or 3-3) was found in 9.4% of the 6,688 participants, in 14.6% of the 2,413 hypertensives and in 6.4% [corrected] of the 4,275 normotensives. During the follow-up period, 133 [corrected] participants died due to cardiovascular disease. After adjustment for systolic blood pressure and other risk factors, left high R-wave conferred an increased risk of cardiovascular death; the hazard ratio among all the participants was 1.88 (95% confidence interval, 1.22-2.89; p < 0.01), that among hypertensives was 1.97 (1.20-3.24; p = 0.01), and that among normotensives was 1.66 (0.69-3.98; p = 0.26). The population attributable risk percent of left high R-wave for cardiovascular death was 7.6% among all participants, 12.4% among hypertensives and 4.1% among normotensives. Left high R-wave on electrocardiogram, irrespective of the level of systolic blood pressure, was a predictive marker for cardiovascular death among community-dwelling Japanese.     

Prognostic value of ST-T abnormalities and left high R waves with cardiovascular mortality in Japanese (24-year follow-up of NIPPON DATA80)

Little is known about the prognostic value of ST-segment depression and/or T wave (ST-T abnormalities) with or without left high R waves on electrocardiogram recorded at rest for death from cardiovascular disease (CVD) in Asian populations. Japanese participants without a history of CVD and free of major electrocardiographic (ECG) abnormalities were followed for 24 years. Subjects were divided into 4 groups based on baseline ECG findings: isolated left high R waves, isolated ST-T abnormalities, ST-T abnormalities with left high R waves, and normal electrocardiogram. Cox proportional hazard model was used to estimate risk of CVD mortality in groups with ECG abnormalities compared to the normal group. Of 8,572 participants (44.4% men, mean age 49.5 years; 55.6% women, mean age 49.4 years), 1,142 had isolated left high R waves, 292 had isolated ST-T abnormalities, and 128 had ST-T abnormalities with left high R waves at baseline. Multivariable-adjusted hazard ratios of ST-T abnormalities with left high R waves for CVD mortality were 1.95 (95% confidence interval 1.25 to 3.04) in men and 2.68 (95% confidence interval 1.81 to 3.97) in women. Isolated ST-T abnormalities increased the risk for CVD death by 1.66 times (95% confidence interval 1.01 to 2.71) in men and 1.62 times (95% confidence interval 1.18 to 2.24) in women. Association of ECG abnormalities with CVD mortality was independent of age, body mass index, systolic blood pressure, serum cholesterol, blood glucose, smoking and drinking, and antihypertensive medication. In conclusion, ST-T abnormalities with or without left high R waves on electrocardiogram recorded at rest constitute an independent predictor of CVD mortality in Japanese men and women.     

Dietary Factors,Dietary Patterns,and Cardiovascular Disease Risk in Representative Japanese Cohorts: NIPPON DATA80/90

Diet is one of the most important factors affecting healthy life expectancy through the onset of cardiovascular disease (CVD) risk as well as various chronic diseases. Because dietary habits and disease structure differ depending on the country, region, and/or race, evidence from each population is required. NIPPON DATA80/90 is a long-term cohort study of a representative Japanese population that participated in national nutrition surveys. Among the many findings of this cohort study, a dietary pattern with higher intake of fruits, vegetables, fish (n-3 polyunsaturated fatty acids), and dietary fiber and lower intake of salt as well as sodium-to-potassium ratio was found to be associated with a lower risk of CVD mortality. The results from our cohort study would be useful for effectively preventing CVD. This article reviews the published studies from the NIPPON DATA80/90 to highlight the significant findings that may be used to develop risk prevention strategies for CVD.     

Lone atrial fibrillation in elderly persons: a marker for cardiovascular risk.

BACKGROUND: The risk of stroke in persons aged 60 years and younger with lone atrial fibrillation (LAF) is no greater than in the general population. The effect of older age on the risk of stroke in persons with LAF is less well established. PARTICIPANTS AND METHODS: The risk of stroke in persons with LAF and without substantial comorbidities was examined in a population-based study at a single institution in Olmsted County, Minnesota, and compared with that in an age- and sex-matched population. The mean age was 74 years (range, 61-97 years). The median duration of follow-up was 9.6 years until death or last follow-up. RESULTS: Of 55 patients, 26 had 31 cardiovascular events during follow-up, occurring a median of 5.1 years after diagnosis (range, 0.7-18 years). Of 11 cerebrovascular events, 6 were transient ischemic attacks and 5 were strokes. The event rates (percentage per person-year) were 0.9% for stroke, 1.1% for transient cerebral ischemia, and 2.6% for myocardial infarction, for a total cardiovascular event rate of 5.0% per person-year. The corresponding rates for the age- and sex-matched control group were 0.2%, 0%, and 1.1%, for a total of 1.3% per person-year. The incidence of total cardiovascular events was significantly greater (P< .01) in those with LAF, although there was no difference in survival. CONCLUSION: Lone atrial fibrillation occurring after age 60 years is a risk marker for a substantial increase in cardiovascular events that warrants consideration for antithrombotic therapy.     

Joint impact of smoking and hypertension on cardiovascular disease and all-cause mortality in Japan: NIPPON DATA80, a 19-year follow-up.

Hypertension and smoking are major risk factors for death due to cardiovascular disease (CVD). These attributions for CVD mortality should be higher in the countries where obesity-related conditions are uncommon. However, the joint effect of these risk factors on CVD and all-cause mortality have not been described. We followed a representative 8,912 Japanese men and women without a history of stroke and heart disease. Participants were categorized into 4 groups as follows: a group of individuals who neither smoked nor had hypertension (HT), a group of current smokers, a group with HT, and a group of current smokers with HT. We further calculated population-attributable fractions (PAF) of CVD and all-cause mortality based on relative hazards assessed by proportional hazard regression models. After 19 years of follow-up, we observed 313 and 291 CVD and 948 and 766 all-cause deaths for men and women, respectively. The PAF of CVD mortality due to smoking or HT were 35.1% for men and 22.1% for women. The PAF of CVD mortality was higher in participants <60 years of age (57.4% for men and 40.7% for women) vs. those who were older (26.3% for men and 18.1% for women). Aggressive attempts to discourage smoking and to curb HT could yield large health benefits in Japan and throughout Asia, particularly for those aged <60 years. Efforts to warn about the adverse consequence of HT and smoking during adolescence and youth could yield the greatest health benefits, since positive behaviors adopted early are more easily continued into middle adulthood and later life.