Min Kuang Tsai

Minimum amount of physical activity for reduced mortality and extended life expectancy: A prospective cohort study

BACKGROUND The health benefits of leisure-time physical activity are well known, but whether less exercise than the recommended 150 min a week can have life expectancy benefits is unclear. We assessed the health benefits of a range of volumes of physical activity in a Taiwanese population. METHODS In this prospective cohort study, 416,175 individuals (199,265 men and 216,910 women) participated in a standard medical screening programme in Taiwan between 1996 and 2008, with an average follow-up of 8·05 years (SD 4·21). On the basis of the amount of weekly exercise indicated in a self-administered questionnaire, participants were placed into one of five categories of exercise volumes: inactive, or low, medium, high, or very high activity. We calculated hazard ratios (HR) for mortality risks for every group compared with the inactive group, and calculated life expectancy for every group. FINDINGS Compared with individuals in the inactive group, those in the low-volume activity group, who exercised for an average of 92 min per week (95% CI 71-112) or 15 min a day (SD 1·8), had a 14% reduced risk of all-cause mortality (0·86, 0·81-0·91), and had a 3 year longer life expectancy. Every additional 15 min of daily exercise beyond the minimum amount of 15 min a day further reduced all-cause mortality by 4% (95% CI 2·5-7·0) and all-cancer mortality by 1% (0·3-4·5). These benefits were applicable to all age groups and both sexes, and to those with cardiovascular disease risks. Individuals who were inactive had a 17% (HR 1·17, 95% CI 1·10-1·24) increased risk of mortality compared with individuals in the low-volume group. INTERPRETATION 15 min a day or 90 min a week of moderate-intensity exercise might be of benefit, even for individuals at risk of cardiovascular disease. FUNDING Taiwan Department of Health Clinical Trial and Research Center of Excellence and National Health Research Institutes.

All-cause mortality attributable to chronic kidney disease: a prospective cohort study based on 462 293 adults in Taiwan

BACKGROUND Both end-stage renal disease and chronic kidney disease are increasing worldwide; however, the full effect of chronic kidney disease is unknown because mortality risks for all five stages are unavailable. We assessed prevalence and mortality risks for all stages of chronic kidney disease and quantified its attributable mortality in Taiwan. METHODS The cohort consisted of 462 293 individuals aged older than 20 years who participated in a standard medical screening programme since 1994. As of Dec 31, 2006, we identified 14 436 deaths. Chronic kidney disease was determined by glomerular filtration rate and urinary protein. We estimated national prevalence in Taiwan from the cohort by adjusting age and educational levels. Hazard ratios (HRs) were calculated with Cox proportionate hazards model. We calculated mortality attributable to chronic kidney disease for national population and for low socioeconomic status. FINDINGS The national prevalence of chronic kidney disease was 11.93% (95% CI 11.66-12.28), but only 3.54% (3.37-3.68) of participants in the cohort were aware of their disorder. Prevalence was substantially higher in the group with low socioeconomic status than in the high status group (19.87% [19.84-19.91] vs 7.33% [7.31-7.35]). 56 977 (12%) of cohort participants had chronic kidney disease; those with disease had 83% higher mortality for all cause (HR 1.83 [1.73-1.93]) and 100% higher for cardiovascular diseases (2.00 [1.78-2.25]), in a cohort that was observed for 13 years with median follow-up of 7.5 years (IQR 4.0-10.1). 10.3% (95% CI 9.57-11.03) of deaths in the entire population were attributable to chronic kidney disease, but 17.5% (16.27-18.67) of deaths in the low socioeconomic status population. 2350 (39%) deaths occurred before 65 years of age in those with chronic kidney disease. Regular users of Chinese herbal medicines had a 20% (odds ratio 1.20 [1.16-1.24]) increased risk of developing chronic kidney disease. INTERPRETATION The high prevalence of chronic kidney disease and its associated all-cause mortality, especially in people with low socioeconomic status, make reduction of this disorder a public-health priority. Promotion of its recognition through the general public knowing their glomerular filtration rate and testing their urine is crucial to reduce premature deaths from all causes and to attenuate this global epidemic.

Is high serum uric acid a risk marker or a target for treatment? Examination of its independent effect in a large cohort with low cardiovascular risk.

BACKGROUND Cohort studies evaluating increased uric acid level as a cardiovascular disease (CVD) risk factor have shown variable results; studies are particularly lacking in lower risk populations. STUDY DESIGN Prospective cohort study. SETTING & PARTICIPANTS 484,568 adults participating in a medical screening program in Taiwan since 1994 were followed up for a median of 8.5 years. Two subgroups were constructed: the first (n = 246,697; 51%) excluded participants with either overt CVD or overt CVD risk factors (including hypertension, diabetes, obesity, and hypertriglyceridemia) and the second (n = 157,238; 32%) further excluded individuals with early-stage CVD risk factors (including prehypertension, prediabetes, overweight, and borderline hypertriglyceridemia). PREDICTOR Serum uric acid. OUTCOMES & MEASUREMENTS All-cause and CVD mortality risk assessed using Cox proportional hazards models for categorical and continuous serum uric acid levels. As applicable, models adjusted for 14 variables. Population-attributable fraction was applied to compare contributions to mortality between high uric acid level and other CVD risk factors. RESULTS In the total cohort, mean age was 41.4 +/- 14.0 years and 26.2% had serum uric acid levels >or=7 mg/dL. Through 2007, there were 16,246 deaths (3.4% of all participants), with 35.2% of deaths occurring in individuals with hyperuricemia. Adjusted HRs associated with serum uric acid levels >or=7 mg/dL for all-cause and CVD mortality were 1.10 (95% CI, 1.04-1.17) and 1.38 (95% CI, 1.20-1.58), respectively. In individuals with hyperuricemia, 64.3% had overt CVD risk factors and 82.5% had either overt or early-stage CVD risk factors. Individuals with serum uric acid levels >or=8 mg/dL without overt CVD risk factors constituted 13.5% of the total study population with hyperuricemia; in analyses excluding those with overt CVD risk factors, serum uric acid level >or=8 mg/dL was significantly associated with all-cause and CVD mortality, with HRs of 1.37 (95% CI, 1.18-1.60) and 2.30 (95% CI, 1.51-3.49), respectively. In the subgroup of those with serum uric acid levels >or=8 mg/dL but who lacked both overt and early-stage CVD risk factors, the HRs for all-cause and CVD mortality were also significant and were 1.39 (95% CI, 1.08-1.78) and 2.38 (95% CI, 1.24-4.54), respectively. HRs for individuals with the same risk profiles but with serum uric acid of 7.0-7.9 mg/dL were not significant. In all groups, inclusion of proteinuria and glomerular filtration rate in models substantially attenuated the association between uric acid level and outcomes. High uric acid levels contributed a relatively insignificant portion to mortality (1.2%) and CVD deaths (4.5%) in this population. LIMITATIONS A single measurement of uric acid was used. CONCLUSION Increased serum uric acid level is a minor, but significant, risk factor for all-cause and CVD mortality. However, except for a small proportion (13.5%), increased serum uric acid level is more a risk marker than a target for treatment and is not an independent risk. Determining appropriate groups to target in clinical trials for uric acid-lowering therapy is critical.

Hepatocellular carcinoma risk prediction model for the general population: The predictive power of transaminases

BACKGROUND Risk prediction models for hepatocellular carcinoma are available for individuals with chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections who are at high risk but not for the general population with average or unknown risk. We developed five simple risk prediction models based on clinically available data from the general population. METHODS A prospective cohort of 428 584 subjects from a private health screening firm in Taiwan was divided into two subgroups-one with known HCV test results (n = 130 533 subjects) and the other without (n = 298 051 subjects). A total of 1668 incident hepatocellular carcinomas occurred during an average follow-up of 8.5 years. Model inputs included age, sex, health history-related variables; HBV or HCV infection-related variables; serum levels of alanine transaminase (ALT), aspartate transaminase (AST), and alfa-fetoprotein (AFP), as well as other variables of routine blood panels for liver function. Cox proportional hazards regression method was used to identify risk predictors of hepatocellular carcinoma. Receiver operating characteristic curves were used to assess discriminatory accuracy of the models. Models were internally validated. All statistical tests were two-sided. RESULTS Age, sex, health history, HBV and HCV status, and serum ALT, AST, AFP levels were statistically significant independent predictors of hepatocellular carcinoma risk (all P < .05). Use of serum transaminases only in a model showed a higher discrimination compared with HBV or HCV only (for transaminases, area under the curve [AUC] = 0.912, 95% confidence interval [CI] = 0.909 to 0.915; for HBV, AUC = 0.840, 95% CI = 0.833 to 0.848; and for HCV, AUC = 0.841, 95% CI = 0.834 to 0.847). Adding HBV and HCV data to the transaminase-only model improved the discrimination (AUC = 0.933, 95% CI = 0.929 to 0.949). Internal validation showed high discriminatory accuracy and calibration of these models. CONCLUSION Models with transaminase data were best able to predict hepatocellular carcinoma risk even among subjects with unknown or HBV- or HCV-negative infection status.

Adiposity, Its Related Biologic Risk Factors, and Suicide: A Cohort Study of 542,088 Taiwanese Adults

Recent studies in Western nations have shown inverse associations between body mass index (BMI, measured as weight (kg)/height (m)(2)) and suicide. However, it is uncertain whether the association is similar in non-Western settings, and the biologic pathways underlying the association are unclear. The authors investigated these issues in a cohort of 542,088 Taiwanese people 20 years of age or older who participated in a health check-up program (1994-2008); there were 573 suicides over a mean 8.1 years of follow up. There was a J-shaped association between BMI and suicide risk (P for the quadratic term = 0.033) but limited evidence of a linear association (adjusted hazard ratio per 1-standard-deviation increase = 0.95 (95% confidence interval: 0.85, 1.06)); compared with individuals whose BMI was 18.5-22.9, adjusted hazard ratios for those with a BMI <18.5 or ≥35 were 1.56 (95% confidence interval: 1.07, 2.28) and 3.62 (95% confidence interval: 1.59, 8.22), respectively. A high waist-to-hip ratio was associated with an increased risk of suicide. There was some evidence for a reverse J-shaped association of systolic blood pressure and high density lipoprotein cholesterol with suicide and an association of higher triglyceride level with increased suicide risk; these associations did not appear to mediate the associations of BMI and waist-to-hip ratio with suicide.

Minimal Amount of Exercise to Prolong Life: To Walk, to Run, or Just Mix It Up?∗

In order for man to succeed in life, God provided two means, education and physical activity. Lack of activity destroys the good condition of every human being, while movement and methodical physical exercise can save it and preserve it. —Plato 400 B.C. [(1,2)][1] For man to assume great

Urine Dipstick to Detect Trace Proteinuria: An Underused Tool for an Underappreciated Risk Marker

In the medical evaluations of healthy individuals, urinalysis receives relatively little attention compared to blood work. However, one finding from the urinalysis--proteinuria--carries a risk far higher than many abnormalities identified from blood studies. 1-4 Even small quantities of albumin in the urine (an albumin-creatinine ratio [ACR] of 30-300 mg/g, often termed “microalbuminuria”) is not only a sign of kidney damage, 5 but is also associated with an increased risk for cardiovascular diseases, 1

High serum iron is associated with increased cancer risk

Epidemiologic studies linking high serum iron with cancer risks are limited and inconclusive, despite evidence implicating body iron in human carcinogenesis. A cohort of 309,443 adults in Taiwan who had no history of cancer had serum iron levels tested at the time of recruitment (1997-2008). Initially measured iron levels were associated with subsequent cancer risk by linking individuals with the National Cancer Registry and National Death File. HRs were calculated by the Cox model. One third of males (35%) and one fifth of females (18%) had high serum iron (≥120 μg/dL), which was associated with a 25% increase in risk for incidence of all cancers [HR, 1.25; 95% confidence interval (CI), 1.16-1.35] and with a 39% increase in risk for mortality from all cancers (HR, 1.39; 95% CI, 1.23-1.57). The relationship between serum iron and cancer risk was a J-shaped one, with higher cancer risk at both ends, either at lower than 60 μg/dL or higher than 120 μg/dL. At the higher end, cancer risk increased by 4% for every 10 μg/dL increment above 80 μg/dL, showing a dose-response relationship, with 60 to 79 μg/dL as a reference level. In a sensitivity analysis, the increases in risk were still observed after the first 5 years of cancer cases were excluded. Liver cancer risk was increased in HBV (-) non-hepatitis B carrier (3-fold) and HBV (+) hepatitis B carrier (24-fold). Lifestyle risks such as smoking, drinking, or inactivity interacted synergistically with high serum iron and significantly increased the cancer risks. The liver (HR, 2.49; 95% CI, 1.97-3.16) and the breast (HR, 1.31; 95% CI, 1.01-1.70) were the two major cancer sites where significant cancer risks were observed for serum iron either ≥120 μg/dL or ≥140 μg/dL, respectively. This study reveals that high serum iron is both a common disorder and a marker of increased risk for several cancers.

The ability of bilirubin in identifying smokers with higher risk of lung cancer: a large cohort study in conjunction with global metabolomic profiling

Purpose: We aimed to identify serum metabolites as potential valuable biomarkers for lung cancer and to improve risk stratification in smokers. Experimental Design: We performed global metabolomic profiling followed by targeted validation of individual metabolites in a case–control design of 386 lung cancer cases and 193 matched controls. We then validated bilirubin, which consistently showed significant differential levels in cases and controls, as a risk marker for lung cancer incidence and mortality in a large prospective cohort composed of 425,660 participants. Results: Through global metabolomic profiling and following targeted validation, bilirubin levels consistently showed a statistically significant difference among healthy controls and lung cancer cases. In the prospective cohort, the inverse association was only seen in male smokers, regardless of smoking pack-years and intensity. Compared with male smokers in the highest bilirubin group (>1 mg/dL), those in the lowest bilirubin group (<0.75 mg/dL) had 55% and 66% increase in risks of lung cancer incidence and mortality, respectively. For every 0.1 mg/dL decrease of bilirubin, the risks for lung cancer incidence and mortality increased by 5% and 6% in male smokers, respectively (both P < 0.001). There was a significant interaction between low serum bilirubin level and smoking on lung cancer risk (Pinteraction = 0.001). Conclusion: Low levels of serum bilirubin are associated with higher risks of lung cancer incidence and mortality in male smokers and can be used to identify higher risk smokers for lung cancer. Clin Cancer Res; 21(1); 193–200. ©2014 AACR.

Attenuating the mortality risk of high serum uric acid: the role of physical activity underused

Background High serum uric acid (sUA) has been associated with increased mortality risks, but its clinical treatment varied with potential side effects. The role of physical activity has received limited attention. Methods A cohort, consisting of 467 976 adults, who went through a standard health screening programme, with questionnaire and fasting blood samples, was successively recruited between 1996 and 2008. High sUA is defined as uric acid above 7.0 mg/dL. Leisure time physical activity level was self-reported, with fully active defined as those with 30 min per day for at least 5 days a week. National death file identified 12 228 deaths with a median follow-up of 8.5 years. Cox proportional model was used to analyse HRs, and 12 variables were controlled, including medical history, life style and risk factors. Findings High sUA constituted one quarter of the cohort (25.6%). Their all-cause mortality was significantly increased [HR: 1.22 (1.15–1.29)], with much of the increase contributed to by the inactive (HR: 1.27 (1.17–1.37)), relative to the reference group with sUA level of 5–6 mg/dL. When they were fully active, mortality risks did not increase, but decreased by 11% (HR: 0.89 (0.82–0.97)), reflecting the benefits of being active was able to overcome the adverse effects of high sUA. Given the same high sUA, a 4–6 years difference in life expectancy was found between the active and the inactive. Conclusions Physical activity is a valuable alternative to pharmacotherapy in its ability to reduce the increases in mortality risks from high sUA. By being fully active, exercise can extend life span by 4–6 years, a level greater than the 1–4 years of life-shortening effect from high sUA.