Impact on visual acuity and psychological outcomes of ranibizumab and subsequent treatment for diabetic macular oedema in Japan (MERCURY).

PURPOSE: The MERCURY study aimed to evaluate the effects on visual acuity and psychological symptoms, and safety, of ranibizumab and subsequent treatment in patients with diabetic macular oedema (DME) and impaired visual acuity (VA). We report data from the prespecified 12-month interim analysis. METHODS: This was a 24-month, phase 4, open-label, single-arm, prospective, observational study conducted at 20 specialised retinal centres in Japan. Participants were 209 patients with DME and impaired VA, not previously treated with either intravitreal or systemic anti-vascular endothelial growth factor (anti-VEGF) agents, who initiated ranibizumab 0.5 mg per investigator discretion. Following ranibizumab administration, patients were treated per routine clinical practice. Other treatments were allowed. The main outcome measure was the mean change in best-corrected VA (BCVA) in logarithmic minimum angle of resolution (logMAR) from baseline to month 12. An exploratory objective was to assess patients' psychological status using the Hospital Anxiety and Depression Scale (HADS). RESULTS: The mean ± standard deviation BCVA at baseline was 0.43 ± 0.39 logMAR. The mean number of injections of ranibizumab and anti-VEGF agents from baseline to month 11 was 3.2 ± 2.0 and 3.6 ± 2.4, respectively. The BCVA change from baseline to 12 months was - 0.08 ± 0.34 logMAR (p = 0.011), showing a significant improvement; the HADS-anxiety score also decreased significantly (p = 0.001) and the depression score decreased numerically (p = 0.080). CONCLUSION: MERCURY study data confirm the effectiveness of real-world treatment initiated with ranibizumab in Japanese patients with DME. In addition, treatment was able to positively influence anxiety via VA improvement.

Increased salt intake is associated with diabetes and characteristic dietary habits: a community-based cross-sectional study in Japan.

We investigated the association of salt intake with lifestyle-related diseases and also the association of habitually consumed foods with salt intake. A cross-sectional study was conducted using data from a baseline survey of 2,129 residents of Yonezawa city (980 males and 1,149 females), Yamagata prefecture. The residents were divided into three groups based on their estimated daily salt intake: low, medium, and high. In both genders, the prevalence of hypertension and diabetes increased in the order of high > medium > low salt intake (trend p<0.001). Similar trends were observed in the prevalence of hyperlipidemia in females and metabolic syndrome in males. The prevalence of diabetes in the high salt intake group was significantly higher than that in the control group (matched from the low and medium salt intake groups), even when confounding factors were excluded by propensity score matching (p<0.01). Network analysis showed that the low salt intake group had a greater tendency to habitually consume various vegetables than the high salt intake group. Our findings reveal that the prevalence of lifestyle-related diseases increased with higher salt intake. We speculate that a dietary shift to multiple vegetable consumption could have salt-lowering effects.

A systematic review and participant-level meta-analysis found little association of retinal microvascular caliber with reduced kidney function.

Previously, variation in retinal vascular caliber has been reported in association with chronic kidney disease (CKD) but findings remain inconsistent. To help clarify this we conducted individual participant data meta-analysis and aggregate data meta-analysis on summary estimates to evaluate cross-sectional associations between retinal vascular caliber and CKD. A systematic review was performed using Medline and EMBASE for articles published until October 2018. The aggregate analysis used a two-stage approach combining summary estimates from eleven studies (44,803 patients) while the individual participant analysis used a one-stage approach combining raw data from nine studies (33,222 patients). CKD stages 3-5 was defined as an estimated glomerular filtration rate under 60 mL/min/1.73m2. Retinal arteriolar and venular caliber (central retinal arteriolar and venular equivalent) were assessed from retinal photographs using computer-assisted methods. Logistic regression estimated relative risk of CKD stages 3-5 associated with a 20 µm decrease (approximately one standard deviation) in central retinal arteriolar and venular equivalent. Prevalence of CKD stages 3-5 was 11.2% of 33,222 and 11.3% of 44,803 patients in the individual participant and aggregate data analysis, respectively. No significant associations were detected in adjusted analyses between central retinal arteriolar and venular equivalent and CKD stages 3-5 in the aggregate analysis for central retinal arteriolar relative risk (0.98, 95% confidence interval 0.94-1.03); venular equivalent (0.99, 0.95-1.04) or individual participant central retinal arteriolar (0.99, 0.95-1.04) or venular equivalent (1.01, 0.97-1.05). Thus, meta-analysis provided little evidence to suggest that cross sectional direct measurements of retinal vascular caliber was associated with CKD stages 3-5 in the general population. Hence, meta-analyses of longitudinal studies evaluating the association between retinal parameters and CKD stages 3-5 may be warranted.

Circadian Clock Gene Polymorphisms and Sleep-Onset Problems in a Population-Based Cohort Study: The Yamagata Study.

A number of genome-wide association studies have investigated sleep phenotypes and disorders in humans. However, the contribution of genetic variation to sleep problems in Japanese populations has remained unclear. Sleep-onset problems are the most common symptom of insomnia. Here, we examined the relationship between single nucleotide polymorphisms (SNPs) of BMAL1 (ARNTL1), CLOCK, CRY1, CRY2, and PER2, which are genes involved in the clock mechanism, and sleep-onset problems in a Japanese general population. This study included 1,397 subjects aged ≥ 40 years who participated in an annual health check-up in Yamagata Prefecture. A total of 80 SNPs of 5 circadian clock genes were analyzed. Multivariate logistic regression analyses identified variant rs11113179 in CRY1 and variants rs1026071 and rs1562438 in BMAL1 as genetic risk factors for sleep induction disorder. These findings suggest that CRY1 and BMAL1 polymorphisms are related to sleep-onset problems in a Japanese general population. However, none of the SNPs remained significant at a stringent level of multiple correction.

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.

Prevalence and Pattern of Geographic Atrophy in Asia: The Asian Eye Epidemiology Consortium.

PURPOSE: Although there have been many population-based studies of age-related macular degeneration (AMD), only limited information is available in Asia on the epidemiology of geographic atrophy (GA). We aimed to determine the prevalence and patterns of GA through an analysis of multiple studies conducted within the Asian Eye Epidemiology Consortium (AEEC). DESIGN: Cross-sectional meta-analyses. PARTICIPANTS: A total of 97 213 individuals aged 40 years and older. METHODS: Data from 22 population-based studies from countries belonging to the AEEC were included. In all studies, AMD was defined on the basis of standardized grading systems. Geographic atrophy was defined as an area of pallor in the fundus with visibility of the underlying choroidal blood vessels and sharply defined borders. Random-effects meta-analysis was performed to estimate overall and age-, gender-, and region-specific pooled prevalence of GA. MAIN OUTCOME MEASURES: Prevalence of GA per 1000 persons. RESULTS: The mean age was 60.8 ± 10.0 years, and 42 673 (43.9%) were male. Overall, a total of 223 individuals (0.2%) had GA. The pooled overall prevalence of GA was 1.57 per 1000 persons (95% confidence interval [CI], 1.04-2.10), which was 3 times less than that of neovascular AMD of 5.20 per 1000 persons (95% CI, 3.97-6.43). Compared with those aged 50 to 59 years, the prevalence of GA increased from 0.34 per 1000 persons (95% CI, 0.07-0.62) to 2.90 per 1000 persons (95% CI, 1.55-4.25) in those aged ≥70 years. The GA prevalence per 1000 persons was similar between urban (2.22; 95% CI, 1.22-3.23) and rural residents (1.33; 95% CI, 0.70-1.96). Geographic atrophy was more prevalent in South Asia (based on studies from India and Nepal, 3.82 per 1000 persons; 95% CI, 1.72-5.93) compared with East Asia (based on studies from China, Korea, Hong Kong, Taiwan, and Japan, and the Singapore Chinese Eye Study, 0.76 per 1000 persons; 95% CI, 0.31-1.22, P = 0.005). CONCLUSIONS: Geographic atrophy is uncommon in Asian populations compared with those of European ancestry. Even within Asia, geographic differences in GA prevalence were seen. The findings of this meta-analysis suggest that better dissection of risk factors in the Asian population for GA may provide insights into the biological pathways that drive these late-stage manifestations, thus suggesting better targets for prevention.

Associations of Frequency of Laughter With Risk of All-Cause Mortality and Cardiovascular Disease Incidence in a General Population: Findings From the Yamagata Study.

BACKGROUND: Positive and negative psychological factors are associated with mortality and cardiovascular disease. This study prospectively investigated associations of daily frequency of laughter with mortality and cardiovascular disease in a community-based population. METHODS: This study included 17,152 subjects ≥40 years old who participated in an annual health check in Yamagata Prefecture. Self-reported daily frequency of laughter was grouped into three categories (≥1/week; ≥1/month but <1/week; <1/month). Associations of daily frequency of laughter with increase in all-cause mortality and cardiovascular disease incidence were determined using Cox proportional hazards modeling. RESULTS: During follow-up (median, 5.4 years), 257 subjects died and 138 subjects experienced cardiovascular events. Kaplan-Meier analysis revealed that all-cause mortality and cardiovascular disease incidence were significantly higher among subjects with a low frequency of laughter (log-rank P < 0.01). Cox proportional hazard model analysis adjusted for age, gender, hypertension, smoking, and alcohol drinking status showed that risk of all-cause mortality was significantly higher in subjects who laughed <1/month than in subjects who laughed ≥1/week (hazard ratio [HR] 1.95; 95% confidence interval [CI], 1.16-3.09). Similarly, risk of cardiovascular events was higher in subjects who laughed ≥1/month but <1/week than in subjects who laughed ≥1/week (HR 1.62; 95% CI, 1.07-2.40). CONCLUSION: Daily frequency of laughter represents an independent risk factor for all-cause mortality and cardiovascular disease in a Japanese general population.

Preoperative factors to select vitrectomy or scleral buckling for retinal detachment in microincision vitrectomy era.

BACKGROUND: To determine the preoperative factors associated with selecting scleral buckling (SB) or pars plana vitrectomy (PPV) to treat rhegmatogenous retinal detachments (RRDs) in the era of microincision vitrectomy surgery. METHODS: A nationwide, multicenter, observational study in the Japan Retinal Detachment Registry was done. From February 2016 to March 2017, 3446 cases were registered, and 3219 among them were analyzed. The factors related to the patient or surgeon were selected; the surgeon's factor included years of experience, number of cases registered, and current activity. The odds ratio (OR) for factors associated with SB or PPV was estimated by a mixed logistic regression model. RESULTS: SB was selected in 24.2% (779/3219), PPV was in 71.5% (2238/3219), and PPV+SB was in 6.3% (202/3219). Multivariate analysis showed that age [< 70 years old, OR 4.27, 95% confidence interval (CI) 2.34-7.79, P < 0.001], visual acuity [1.0+ (OR 7.41, 95% CI 3.47-15.82, P < 0.001)], pseudo-phakia (OR 4.83, 95%CI 2.11-10.56, P < 0.001), retinal tear (OR 6.92, 95% CI 4.83-9.92, P < 0.001), breaks at/near the vitreous base (OR 8.07, 95% CI 3.50-18.62, P < 0.001), 90+° retinal tear (OR 108.24, 95% CI 7.44-1574.34, P < 0.001), and number of breaks 4+ (OR 3.15, 95% CI 1.95-5.09, P < 0.001), were significantly associated with selecting PPV over SB. The surgeons' activity defined as the number of cases experienced during the registry period was related to the selection of PPV (OR 3.83, 95% CI 2.11-6.93, P < 0.001). CONCLUSIONS: The choice of PPV for the RRD was associated not only with patients' preoperative factors but also the surgeon's activity. Active surgeons selected PPV more than SB.

Relationship between social support status and mortality in a community-based population: a prospective observational study (Yamagata study).

BACKGROUND: Social support, defined as the exchange of support in social relationships, plays a vital role in maintaining healthy behavior and mitigating the effects of stressors. This study investigated whether functional aspect of social support is related to 5-year mortality in health checkup participants. METHODS: This study recruited 16,651 subjects (6797 males, 9854 females). Social support was evaluated using five-component questions: Do you have someone 1) whom you can consult when you are in trouble? 2) whom you can consult when your physical condition is not good? 3) who can help you with daily homework? 4) who can take you to hospital when you don't feel well? and 5) who can take care of you when you are ill in bed? The association between the component of social support and all-cause and cardiovascular mortality was examined using Cox proportional hazard analysis. RESULTS: The percentage of subjects without social support components was 7.7-15.0%. They were more likely to be male, non-elderly, and living alone. During the follow-up period, there were 166 all-cause and 38 cardiovascular deaths. Cox proportional analysis adjusted for confounders showed that only the lack of support for transportation to hospital was significantly associated with all-cause (hazard ratio [HR] 2.01, 95% confidence interval [CI] 1.26-3.05) and cardiovascular mortality (HR 3.30, 95% CI 1.41-6.87). These associations were stronger in males than females. CONCLUSION: This study showed that the lack of social support for transportation to the hospital was independently associated with all-cause and cardiovascular mortality in a community-based population.

Association between presence of 20 or more natural teeth and all-cause, cancer-related, and cardiovascular disease-related mortality: Yamagata (Takahata) prospective observational study.

BACKGROUND: Several studies have surveyed the relationship between the presence of ≥ 20 natural teeth and mortality. However, very few have evaluated this association over a long-term follow-up of more than ten years within a large population in Japan. This study aimed to prospectively confirm the associations between mortality and the presence of ≥ 20 natural teeth within a community-based population in Japan. METHODS: A prospective observational study including 2208 participants aged ≥ 40 years was conducted in Takahata Town, Japan, between May 2005 and December 2016. All participants answered a self-administered questionnaire to provide their background characteristics, including their number of teeth. The participants were classified into two categories based on their self-reported number of teeth (< 20 and ≥ 20 teeth). Hazard ratios (HR) and 95% confidence intervals (CI) were calculated using Cox proportional-hazards regression model to assess risk factors for all-cause, cancer-, and cardiovascular disease-related mortality. RESULTS: The total follow-up period was 131.4 ± 24.1 months (mean ± SD). After adjusting for covariates, the risk of all-cause mortality was significantly higher in the group with < 20 teeth than in those with ≥ 20 teeth (HR = 1.604, 95% CI 1.007-2.555, p = 0.047). However, the risk of cancer- and cardiovascular disease-related mortalities was not statistically significant between the two groups. CONCLUSION: In this study, participants with < 20 teeth had a significantly higher risk of all-cause mortality, although the difference was borderline significant. These results emphasize the importance of having ≥ 20 natural teeth for a healthy life expectancy.

The association between genotypes of urate transporter-1, Serum uric acid, and mortality in the community-based population: the Yamagata (Takahata) Study.

BACKGROUND: The urate transporter-1 (URAT1) is crucial in developing hyperuricemia via reabsorption of uric acid in renal tubules, and its function is regulated by several single nucleotide polymorphisms (SNPs) within SLC22A12 gene encoding URAT1. This study investigated whether the genetic predisposition of URAT1 is associated with the mortality in general population. METHODS: This study enrolled 1596 participants (male 45%, mean age 61 years) who registered at local health checkup in Takahata, Japan, and the association between the rs505802 genotypes in SLC22A12 gene and the 7-year mortality, was examined. RESULTS: The serum uric acid levels (mean ± SD) at baseline in the subjects with GG and AG + AA genotypes of rs505802 were 5.1 ± 1.3 mg/dL and 5.0 ± 1.5 mg/dL, respectively. Kaplan-Meier analysis revealed that the mortality was nonsignificantly higher in the subjects with GG genotype than in those with AG + AA genotype (P = 0.09). Cox proportional hazard model adjusted with age, gender, renal function, comorbidities, and other possible confounders, demonstrated that the GG genotype was significantly associated with the mortality [hazard ratio (HR) 2.23, 95% confidence interval (CI) 1.05-4.85, (vs. AG + AA genotype)]. Furthermore, adjustment with serum uric acid levels, along with aforementioned confounders retained the significant association (HR 2.26, 95% CI 1.05-4.85). CONCLUSIONS: This study revealed that the genetic predisposition of URAT1 was independently associated with mortality in the Japanese community-based population. This association might be due to the mechanism independent of serum uric acid levels.

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.

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.

Corneal vesicles accumulate collagen VI associated with tissue remodeling in apolipoprotein a-I deficiency: a case report.

BACKGROUND: Apo A-I deficiency clinically shows low serum levels of HDL cholesterol and corneal opacity at a young age. Histopathological evaluations of affected corneas are not enough, and the mechanism of corneal opacity is still unclear. CASE PRESENTATION: A 61-year-old woman suffered from blurred vision with a corneal opacity. She had significantly reduced serum levels of high-density lipoprotein cholesterol and Apo A-I, stenosis of the coronary arteries, and ischemic heart failure. On genetic examination, a homozygous mutation of Apo A-ITsukuba was identified. Histopathological examination of the corneal button after PKP showed numerous vesicles in the corneal stroma, which were more prominent in the deep stroma than in the shallow stroma. Collagen VI was observed in some of those vesicles. CONCLUSION: We experienced a rare case of corneal opacity due to Apo A-I deficiency. Our histopathological findings indicated that structural changes in corneal collagen fibrils contribute to the formation of stromal vesicles.

Gene-environment interactions in obesity: implication for future applications in preventive medicine.

Obesity is associated with environmental factors; however, information about gene-environment interactions is lacking. We aimed to elucidate the effects of gene-environment interactions on obesity, specifically between genetic predisposition and various obesity-related lifestyle factors, using data from a population-based prospective cohort study. The genetic risk score (GRS) calculated from East Asian ancestry single-nucleotide polymorphisms was significantly associated with the body mass index (BMI) at baseline (P<0.001). Significant gene-environment interactions were observed for six nutritional factors, alcohol intake, metabolic equivalents-hour per day and the homeostasis model assessment ratio. The GRS altered the effects of lifestyle factors on BMI. Increases in the BMI at baseline per unit intake for each nutritional factor differed depending on the GRS. However, we did not observe significant correlations between the GRS and annual changes in BMI during the follow-up period. This study suggests that the effects of lifestyle factors on obesity differ depending on the genetic risk factors. The approach used to evaluate gene-environment interaction in this study may be applicable to the practice of preventive medicine.

Health management in cancer survivors: Findings from a population-based prospective cohort study-the Yamagata Study (Takahata).

The number of cancer survivors is increasing; however, optimal health management of cancer survivors remains unclear due to limited knowledge. To elucidate the risk of non-communicable diseases, and the effect of lifestyle habits on risk of non-communicable diseases, we compared cancer survivors and those who never had cancer (non-cancer controls) using a population-based prospective cohort study. The baseline survey of 2292 participants was carried out from 2004 to 2006, and the follow-up survey of 2124 participants was carried out in 2011. We compared the baseline characteristics and the risk of non-communicable diseases between cancer survivors and non-cancer controls. Analyzed participants included 124 cancer survivors (men/women, 57/67), and 2168 non-cancer controls (939/1229). Several lifestyle factors and nutritional intake significantly differed between survivors and non-cancer controls, although smoking status did not differ between the groups (P = 0.30). Univariate logistic regression analysis showed increased risk of death (odds ratio [OR], 3.64; 95% confidence interval [CI], 2.19-6.05) and heart disease (OR, 2.60; 95% CI, 1.06-6.39) in cancer survivors. Increased risk of heart disease was also significant (OR, 2.95; 95% CI, 1.05-8.26; P = 0.04) in the multivariate analysis of the smoking-related cancer subgroup. Current smoking significantly increased risk of death (OR, 2.42; 95% CI, 1.13-5.18). Specific management should be implemented for cancer survivors. More intense management against smoking is necessary, as continued smoking in cancer survivors may increase the risk of second primary cancer. Moreover, cancer survivors are at a high risk of heart disease; thus, additional care should be taken.

Lower aldosterone-renin ratio is a risk factor for total and cancer death in Japanese individuals: the Takahata study.

OBJECTIVE: A higher plasma aldosterone-renin ratio (ARR) is an established marker for screening for primary aldosteronism (PA). The association between higher ARR and mortality in a general population has not been fully explored. We here examined whether higher ARR is a risk factor for total and cause-specific mortality in a Japanese population. SUBJECTS AND METHODS: A population-based, longitudinal study of 1,310 Japanese individuals (age: 63·9 ± 9·8 years) enrolled in the Takahata study between 2004 and 2006 and followed for up to 8 years. The incidence and causes of death were monitored annually until 10 January 2012 (median follow-up: 2691 days). RESULTS: During the follow-up period, 64 subjects died. Kaplan-Meier analysis showed a significantly increased risk for total and cancer mortality in subjects with lower ARR (log-rank P < 0·001). Cox's proportional hazard model analyses with adjustment for age and gender showed that lower ARR was associated with increased total and cancer mortality in subjects with low (≦72) vs high (>72) ARR (hazard ratios and 95% confidential intervals: 2·56, 1·44-4·56 and 2·78, 1·16-6·65, respectively). CONCLUSIONS: Lower ARR was a significant and independent risk factor for increased total and cancer mortality in this Japanese population. Subjects with higher ARR were not-at-risk for total death in general. These findings increase the necessity for identifying people with PA from those with higher ARR. People with higher ARR without PA may be at very low risk for total and cancer death.

Likelihood ratio-based integrated personal risk assessment of type 2 diabetes.

To facilitate personalized health care for multifactorial diseases, risks of genetic and clinical/environmental factors should be assessed together for each individual in an integrated fashion. This approach is possible with the likelihood ratio (LR)-based risk assessment system, as this system can incorporate manifold tests. We examined the usefulness of this system for assessing type 2 diabetes (T2D). Our system employed 29 genetic susceptibility variants, body mass index (BMI), and hypertension as risk factors whose LRs can be estimated from openly available T2D association data for the Japanese population. The pretest probability was set at a sex- and age-appropriate population average of diabetes prevalence. The classification performance of our LR-based risk assessment was compared to that of a non-invasive screening test for diabetes called TOPICS (with score based on age, sex, family history, smoking, BMI, and hypertension) using receiver operating characteristic analysis with a community cohort (n = 1263). The area under the receiver operating characteristic curve (AUC) for the LR-based assessment and TOPICS was 0.707 (95% CI 0.665-0.750) and 0.719 (0.675-0.762), respectively. These AUCs were much higher than that of a genetic risk score constructed using the same genetic susceptibility variants, 0.624 (0.574-0.674). The use of ethnically matched LRs is necessary for proper personal risk assessment. In conclusion, although LR-based integrated risk assessment for T2D still requires additional tests that evaluate other factors, such as risks involved in missing heritability, our results indicate the potential usability of LR-based assessment system and stress the importance of stratified epidemiological investigations in personalized medicine.