Development of a Novel Multidimensional Measure of Aging to Predict Mortality and Morbidity in the Prospective MJ Cohort.

BACKGROUND: Although biological aging has been proposed as a more accurate measure of aging, few biological aging measures have been developed for Asians, especially for young adults. METHODS: A total of 521 656 participants were enrolled in the MJ cohort (1996-2011) and were followed until death, loss-to-follow-up, or December 31, 2011, whichever came first. We selected 14 clinical biomarkers, including chronological age, using a random forest algorithm, and developed a multidimensional aging measure (MDAge). Model performance was assessed by area under the curve (AUC) and internal calibration. We evaluated the associations of MDAge and residuals from regressing MDAge on chronological age (MDAgeAccel) with mortality and morbidity, and assessed the robustness of our findings. RESULTS: MDAge achieved an excellent AUC of 0.892 in predicting all-cause mortality (95% confidence interval [CI]: 0.889-0.894). Participants with higher MDAge at baseline were at a higher risk of death (per 5 years, hazard ration [HR] = 1.671, 95% CI: 1.662-1.680), and the association remained after controlling for other variables and in different subgroups. Furthermore, participants with higher MDAgeAccel were associated with shortened life expectancy. For instance, compared to men who were biologically younger (MDAgeAccel ≤ 0) at baseline, men in the highest tertiles of MDAgeAccel had shortened life expectancy by 17.23 years. In addition, higher MDAgeAccel was associated with having chronic disease either cross-sectionally (per 1-standard deviation [SD], odds ratio [OR] = 1.564, 95% CI: 1.552-1.575) or longitudinally (per 1-SD, OR = 1.218, 95% CI: 1.199-1.238). CONCLUSION: MDAge accurately predicted mortality and morbidity, which has great potential in the early identification of individuals at higher risk and therefore promoting early intervention.

Converting health risks into loss of life years - a paradigm shift in clinical risk communication.

For facilitating risk communication in clinical management, such a ratio-based measure becomes easier to understand if expressed as a loss of life expectancy. The cohort, consisting of 543,410 adults in Taiwan, was recruited between 1994 and 2008. Health risks included lifestyle, biomarkers, and chronic diseases. A total of 18,747 deaths were identified. The Chiang's life table method was used to estimate a loss of life expectancy. We used Cox regression to calculate hazard ratios (HRs) for health risks. The increased mortality from cardio-metabolic risks such as high cholesterol (HR=1.10), hypertension (HR=1.48) or diabetes (HR=2.02) can be converted into a loss of 1.0, 4.4, and 8.9 years in life expectancy, respectively. The top 20 of the 30 risks were associated with a loss of 4 to 10 years of life expectancy, with 70% of the cohort having at least two such risk factors. Smoking, drinking, and physical inactivity each had 5-7 years loss. Individuals with diabetes or an elevated white count had a loss of 7-10 years, while prolonged sitting, the most prevalent risk factor, had a loss of 2-4 years. Those with diabetes (8.9 years) and proteinuria (9.1 years) present at the same time showed a loss of 16.2 years, a number close to the sum of each risk. Health risks, expressed as life expectancy loss, could facilitate risk communication. The paradigm shift in expressing risk intensity can help set public health priorities scientifically to promote a focus on the most important ones in primary care.

Loss of Life Expectancy by 10 Years or More From Elevated Aspartate Aminotransferase: Finding Aspartate Aminotransferase a Better Mortality Predictor for All-Cause and Liver-Related than Alanine Aminotransferase.

OBJECTIVES: Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are 2 commonly ordered liver function tests, and ALT has long been considered more liver-specific than AST. Between the 2, the one which is better in predicting liver or non-liver-related mortality remains unsettled. METHODS: The cohort, 416,122 adults, came from a self-paying comprehensive health surveillance program during 1994-2008 and was followed up till 2008. Mortality came from National Death Index, with 10,412 deaths identified. Hazard ratios (HRs), computed by Cox model, and life expectancy, by life table method, were presented for 5 levels of AST and ALT with elevated AST or ALT defined as ≥40 IU/L. Liver disease included liver cancer and other liver conditions. RESULTS: There were 3 times more elevated ALT (15.4%) than AST (5.7%). However, those with elevated AST had higher mortality for all-cause (HR = 2.44), for liver disease (HR = 27.2), and for liver cancer (HR = 47.6) than its ALT counterparts (HR = 1.69, 10.8, and 20.2, respectively). Elevated AST also lost more years of life expectancy (10.2) than those lost by ALT (5.2) and larger than most common risks. Elevated AST had increased mortality from all cancers (HR = 3.57), stroke (HR = 1.36), respiratory diseases (HR = 1.34), and injuries (HR = 1.82), other than just liver disease. All-cause mortality remained significantly increased, when high risk groups were excluded, such as frequent drinkers, hepatitis carriers, those died from nonmedical conditions, those died in the first 3 years, or advanced fibrosis index based on 4 factors or aspartate transaminase-to-platelet ratio index. Results were consistent between those returned for second visits and those analyzed in initial visits. DISCUSSION: Those with elevated AST (≥40 IU/L) had life expectancy cut short by 10.2 years, doubled the number of years lost with elevated ALT. For all-cause and for liver-related mortality, AST was an important predictor, better than ALT.

Cancer risk associated with chronic diseases and disease markers: prospective cohort study.

OBJECTIVES: To assess the independent and joint associations of major chronic diseases and disease markers with cancer risk and to explore the benefit of physical activity in reducing the cancer risk associated with chronic diseases and disease markers. DESIGN: Prospective cohort study. SETTING: Standard medical screening program in Taiwan. PARTICIPANTS: 405 878 participants, for whom cardiovascular disease markers (blood pressure, total cholesterol, and heart rate), diabetes, chronic kidney disease markers (proteinuria and glomerular filtration rate), pulmonary disease, and gouty arthritis marker (uric acid) were measured or diagnosed according to standard methods, were followed for an average of 8.7 years. MAIN OUTCOME MEASURES: Cancer incidence and cancer mortality. RESULTS: A statistically significantly increased risk of incident cancer was observed for the eight diseases and markers individually (except blood pressure and pulmonary disease), with adjusted hazard ratios ranging from 1.07 to 1.44. All eight diseases and markers were statistically significantly associated with risk of cancer death, with adjusted hazard ratios ranging from 1.12 to 1.70. Chronic disease risk scores summarizing the eight diseases and markers were positively associated with cancer risk in a dose-response manner, with the highest scores associated with a 2.21-fold (95% confidence interval 1.77-fold to 2.75-fold) and 4.00-fold (2.84-fold to 5.63-fold) higher cancer incidence and cancer mortality, respectively. High chronic disease risk scores were associated with substantial years of life lost, and the highest scores were associated with 13.3 years of life lost in men and 15.9 years of life lost in women. The population attributable fractions of cancer incidence or cancer mortality from the eight chronic diseases and markers together were comparable to those from five major lifestyle factors combined (cancer incidence: 20.5% v 24.8%; cancer mortality: 38.9% v 39.7%). Among physically active (versus inactive) participants, the increased cancer risk associated with chronic diseases and markers was attenuated by 48% for cancer incidence and 27% for cancer mortality. CONCLUSIONS: Chronic disease is an overlooked risk factor for cancer, as important as five major lifestyle factors combined. In this study, chronic diseases contributed to more than one fifth of the risk for incident cancer and more than one third of the risk for cancer death. Physical activity is associated with a nearly 40% reduction in the cancer risk associated with chronic diseases.

Liver Fat, Hepatic Enzymes, Alkaline Phosphatase and the Risk of Incident Type 2 Diabetes: A Prospective Study of 132,377 Adults.

Previous studies have reported inconsistent results of the associations of alanine transaminase (ALT), aspartate transaminase (AST), gamma-glutamyltransferase (GGT) and alkaline phosphatase (ALP) with incident type 2 diabetes (diabetes hereafter). We aimed to resolve the controversy by taking nonalcoholic fatty liver disease (NAFLD) into account. The study population comprised 132,377 non-diabetic individuals (64,875 men and 67,502 women) aged 35-79 who had two or more health examinations during 1996-2014. A total of 6,555 incident diabetes (3,734 men and 2,821 women) were identified, on average, over 5.8 years of follow-up. Cox regression was used to calculate the hazard ratio (HR) for incident diabetes, adjusting for classical confounders. The risk of incident diabetes was significantly associated with NAFLD [HR = 2.08 (men) and 2.65 (women)]. Elevated ALT, AST, GGT and ALP were also significantly associated with the increased risk of diabetes, with HRs of 1.27, 1.23, 1.58 and 1.37, respectively, in men, and 1.56, 1.18, 1.48 and 1.44, respectively in women. Our results suggest that NAFLD, ALT, AST, GGT and ALP are independent predictors for incident diabetes in both men and women.

Diabetes with early kidney involvement may shorten life expectancy by 16 years.

This study aimed to identify the excess risks associated with diabetic patients with early kidney involvement (early diabetic kidney disease). The mortality risks of early diabetic kidney disease, defined as diabetes in early stages 1-3 chronic kidney disease (CKD), were assessed from a cohort of 512,700 adults in Taiwan participating in a health surveillance program from 1994-2008. Three related groups were identified and compared: diabetes without CKD, early diabetic kidney disease, and early CKD without diabetes. Deaths were ascertained through the National Death Registry. One-third of diabetics had early kidney disease, and approximately two-thirds of patients were classified with early CKD due to proteinuria. Patients with early diabetic kidney disease had more lifestyle risks such as inactivity or obesity, which characteristically amplified excess mortality by up to five times. The three-fold increase in all-cause mortality (hazard ratio 3.16) and a 16-year loss in life expectancy made early diabetic kidney disease a serious and yet often overlooked disease, with most patients unaware of their kidney involvement. Mortality for early diabetic kidney disease was nearly twice as high as that for early CKD (hazard ratio 2.01) or diabetes without CKD (hazard ratio 1.79). The 16-year life span loss is much worse than individually from early CKD (six years) or diabetes (ten years). Thus, identifying early proteinuria among diabetic patients and realizing the importance of reducing lifestyle risks like inactivity is a clinical challenge, but can save lives.

Physical activity to overcome the adversity of widowhood: Benefits beyond physical health.

Widowhood has been increasingly encountered because of increasing longevity of women, often characterized by social stigmatization and poor physical and mental health. However, applied research to overcome its adversity has been quite limited. The goal of this study is to explore the role of physical activity in improving the health of widows.A cohort of 446,582 adults in Taiwan who successively participated in a comprehensive medical screening program starting in 1994, including 232,788 women, was followed up for mortality until 2008. Each individual provided detailed health history, and extensive lab tests results.The number of widows increased with time trend. Every other woman above age 65 was a widow (44%). Widows were less active, more obese, and smoked and drank more, had sleep problems, were more depressed with taking sedatives or psychoactive drugs, leading to more suicides. In the global development of health policies by World Health Organization (WHO), physical activity is one of the main factors to reverse poor health. The poor health of inactive widow was mitigated when becoming fully active in this study. Exercise not only reduced the observed 18% increase in all-cause mortality, but also gained 4 years and as much as 14% mortality advantage over the married but inactive. More importantly, becoming physically active energized their mental status, improved sleep quality and quantity, reduced depressions and the need for psychoactive drugs, and increased socialization circles.Widows, a rapidly growing and socially stigmatized group, suffered from social and financial inequality and tended to develop poorer health. Sustained physical activity could be one of the ways for them to overcome and reverse some of the physical and mental adversities of widowhood, and improve their quality and quantity of life.

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.

Attributable mortality burden of metabolic syndrome: comparison with its individual components.

AIM: To estimate the national prevalence, mortality risk and population mortality burden of metabolic syndrome, and compare the values with those of its individual components. METHODS AND RESULTS: A total of 486,341 apparently healthy adults who went through a screening programme in Taiwan were recruited from 1994 onwards. As of 2007, 15,268 deaths had occurred at least one year after the examination. Six definitions of metabolic syndrome were used. Components of metabolic syndrome include obesity, hypertension, hyperglycaemia, dyslipidaemia and albuminuria. Hazard ratios (HRs) were calculated using the Cox proportional hazard model. The population mortality burden considered both national prevalence and HRs. The national prevalence of metabolic syndrome defined by the Adult Treatment Panel (ATP) III was 16.3%, the HR for all causes was 1.36 (95%, CI 1.31-1.41) and the HR for cardiovascular disease (CVD) was 1.63 (95%, CI 1.51-1.77). The population mortality burden of metabolic syndrome was 5.5% for all causes, in contrast to 9.0% for hypertension, 8.9% for albuminuria, 6.6% for diabetes, 3.5% for dyslipidaemia and 1.5% for obesity. For CVD it was 9.4%, lower than 10.7% for albuminuria and 25.0% for hypertension. CONCLUSION: The mortality burden of metabolic syndrome was relatively small at national level. Three of the five components of metabolic syndrome alone, namely hypertension, diabetes and albuminuria, contributed more than metabolic syndrome to all-cause mortality. Successful management of any of these three components would have achieved a greater impact on mortality than management of metabolic syndrome.

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.

The reduction of tuberculosis risks by smoking cessation.

BACKGROUND: Smoking is known to aggravate tuberculosis (TB), but such information has been ignored in clinical practice, as it was not thought to be relevant. The aim of this study is to assess the benefits of smoking cessation on TB mortality reduction. METHODS: The study attempts to quantify smokers' risks on subsequent TB mortality and the change in such risks after smokers quit smoking. In this prospective cohort study, the TB mortality risks of smokers, never smokers and former smokers were compared, by using the Cox proportional model to estimate the hazard ratio (HR) of TB.The cohort, consisting of 486,341 adults, participated in standard medical screening programs since 1994, including 5,036 with self-reported TB history. Of 15,268 deaths identified as of 2007, 77 were coded as TB. RESULTS: Smokers with self-reported TB history (1.2%) had very high TB mortality (HR = 44.02). Among those without self-reported TB history, smoking increased TB mortality by nine-fold (HR = 8.56), but when they quit smoking, the risk was reduced by more than half (65%), to a level not different from those who had never smoked. The overwhelming majority of TB deaths (83%) occurred among those without self-reported TB history. Given the high smoking prevalence and the high HR, smoking accounted for more than one-third (37.7%) of TB mortality in Taiwan. Smokers reported less TB history but died more from TB than those who had never smoked. CONCLUSIONS: Smokers had very high TB mortality, as much as nine times those who had never smoked, but once they quit, the risk reduced substantially and was similar to those who never smoked. Smoking cessation has benefits to the smokers far beyond reducing TB risk, but successful tobacco control could favorably impact the TB mortality rate and reduce this public health burden, which has long haunted the Taiwanese population. Smoking cessation could reduce nearly one-third of tuberculosis deaths.

Cancer risks from betel quid chewing beyond oral cancer: a multiple-site carcinogen when acting with smoking.

OBJECTIVES: This cohort study is to assess the extent of cancer risks of betel quid chewing (without tobacco added) beyond oral cancer, as such information was limited from case-control studies. METHODS: The cohort, selected from participants in a medical screening program since 1994, consisted of 177,271 adult men with 19.2% chewers of betel quid. As of 2006, out of 4,840 deaths, 1,901 cancer deaths were identified. Mortality hazard ratios (HR) were estimated by Cox proportional hazard model. Life expectancy was calculated by life table method. RESULTS: One-third of smokers chewed (33%) but most of chewers smoked (90%). Risk for all cancer doubled among chewers (HR = 2.00). Risks of at least six cancer sites were increased among chewers: oral cavity (HR = 12.52), esophagus (HR = 5.64), liver (HR = 2.27), pancreas (HR = 2.67), larynx (HR = 6.24), and lung (HR = 2.43) with risks increased with increasing betel quid amount consumed. All-cancer age-adjusted mortality rates in Taiwan increased 25%, including 223% increase in oral cancer, during the last 20 years when chewing rate increased five- to tenfolds. Chewing on top of smoking increased the risks synergistically, and these two were responsible for at least half (50%) of all cancer deaths among 2 million chewers in Taiwan. Life expectancy of chewers was shorter than non-chewers by 5.93 years at age 20 and 5.55 years at age 40. CONCLUSION: In addition to oral cancer, significant increases were seen among chewers for cancer of the esophagus, liver, pancreas, larynx, lung, and all cancer. Chewing and smoking, as combined by most chewers, interacted synergistically and was responsible for half of all cancer deaths in this group. They were responsible for the recent increases in oral, esophageal, pancreatic, and liver cancer in Taiwan. Chewing and smoking shortened their life span by nearly 6 years.

Are Asians at greater mortality risks for being overweight than Caucasians? Redefining obesity for Asians.

OBJECTIVES: To assess whether overweight Asians, assessed on the basis of WHO criteria, are at greater mortality risk than overweight Caucasians, and to determine whether alternative cut-off points (BMI = 23.0-24.9 kg/m2 for overweight and BMI >or= 25.0 kg/m2 for obesity) suggested by the WHO Western Pacific Regional Office are appropriate. DESIGN: The cohort was followed prospectively until the end of 2001. All-cause and CVD mortality risks of the overweight and obese group, relative to the reference group (BMI = 18.5-24.9 or 18.5-22.9 kg/m2), were assessed using Cox regression analysis, adjusting for age, smoking and gender. Excess deaths were estimated with a method proposed by the US Centers for Disease Control and Prevention. SETTING: National Health Interview Survey (NHIS 2001) and a middle-aged perspective cohort in Taiwan. SUBJECTS: Subjects comprised 36 386 civil servants and school teachers, aged 40 years and older, who underwent a medical examination during 1989-1992. RESULTS: In the WHO-defined overweight group, Asians showed a significant increase in all-cause mortality risk compared with Caucasians. Asians showed risks equivalent to Caucasians' at lower BMI (around 5 units). Every unit of BMI increase, at 25.0 kg/m2 or above, was associated with a 9 % increase in relative mortality risk from all causes. Applying a cut-off point of 25.0 kg/m2 for obesity would result a prevalence of 27.1 %, while the traditional WHO cut-off point of 30.0 kg/m2 yielded obesity prevalence of 4.1 %. Excess deaths due to obesity accounted for 8.6 % of all deaths and 21.1 % of CVD deaths, based on the alternative cut-offs. CONCLUSIONS: In this Asian population, significant mortality risks started at BMI >or= 25.0 kg/m2, rather than at BMI >or= 30.0 kg/m2. The study supports the use of BMI >or= 25.0 kg/m2 as a new cut-off point for obesity and BMI = 23.0-24.9 kg/m2 for overweight. The magnitude of obesity-attributable deaths has been hitherto under-appreciated among Asians.

The effects of pre-disease risk factors within metabolic syndrome on all-cause and cardiovascular disease mortality.

The metabolic syndrome has been criticized for being "polluted with the inclusion of frank "diseases" with "pre-diseases". We assessed the effect of a single and a combination of "pre-disease" risk factors of metabolic syndrome on the overall and cardiovascular disease (CVD) mortality. These pre-disease risk factors included pre-diabetes, pre-hypertension, overweight and borderline hypertriglycerdemia and were defined as: fasting glucose at 110-125 mg/dL, systolic blood pressure at 120-139 mmHg, body mass index at 25-29.9 kg/m(2) and serum triglyceride at 150-199 mg/dL, respectively. The metabolic syndrome in this paper was based on the version defined by the ATP III. The cohort consisted of 35,259 adults (>==40 years) with a medium follow-up of 15 years. Relative risks (RRs) for all-causes, CVD and "CVD plus diabetes" mortality were calculated with the Cox proportional hazards model. Prevalence of the pre-disease risk factors (40.2%) was nearly four times larger than the metabolic syndrome (10.6%). Individual pre-disease risk factor was associated with significant increases of 13% and 67% (pre-diabetes), 22% and 62% (pre-hypertension), 23% and 32% (overweight) and 17% and 46% (borderline hypertriglyceridemia) on all-cause and "CVD plus diabetes" mortality, respectively. Smoking had comparable risks as "pre-diseases", and, as such, should also be considered as the fifth "pre-disease". Like metabolic syndrome, each "Pre-disease" is a major and significant risk factor for all cause and cardiovascular mortality, but unlike metabolic syndrome, the definition or clinical follow up of "Pre-disease" is simple and straightforward. Recognizing each of the four "pre-disease" as a clinical entity, a hitherto sub-clinical status but involving significantly increased mortality, can alert and justify early intervention through changing lifestyle and modifying biologic risk factors.

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.

Assessing physical activity in an Asian country: low energy expenditure and exercise frequency among adults in Taiwan.

Leisure-time physical activity (LTPA) has been closely related to health improvement. The under-appreciation for energy output by nutritionists stems in part from limited data expressed in caloric equivalent. We converted the frequency, duration, and intensity of LTPA, reported from 15,390 adults in the Taiwan National Health Interview Survey 2001, into kilocalories (kcal). Half of Taiwanese adults admit to no LTPA. Women, lower education or income, younger age, smokers and chewers of betel quid; exercised significantly less than their counterparts. Less than 1/5 (18.9%) of the population in Taiwan was physically active at >or=750 kcal/week, and only 1/7 (13.9%) reached a more desirable goal of >or=1,000 kcal/week, compared with 1/3 in the U.S. The most disconcerting finding was the Taiwan unique U-shaped prevalence for males, with the 25-44 age group being the least active, >or=65 age group being the most active; and S-shaped for females, lowest at age 18-24 years and highest at the two older groups (45-64 and >or=65 years). LTPA was under-appreciated, particularly among the most productive work force (25-44-year group), who exercised with a prevalence only 1/4 of their U.S. counterparts. Expressing LTPA in kcal makes direct comparison easier. Invoking a goal of >or=750 kcal/week for Asians, attainable by exercising 4 hours/week, can facilitate nutritionists in assessing LTPA adequacy. Currently, 4/5 of adults in Taiwan failed to reach this goal. Recognizing the concept of cumulative energy expenditure, in contrast to disciplined daily work for 5 or more days, will encourage the infrequent exercisers such as "weekend warriors" to continue with their activities.

Making hypertensive smokers motivated in quitting: developing 'blood pressure equivalence of smoking'.

OBJECTIVE: To express the increased risk from smoking in terms of 'blood pressure' so that hypertensive smokers are motivated into quitting. METHODS: Mortality risks of smokers were compared with nonsmokers in a large worker cohort in Taiwan (n = 23755 with a 17-year follow-up) for all-cause and for cardiovascular diseases. The blood pressure equivalence of smoking was then identified by the difference in mortality risks between smokers and nonsmokers. RESULTS: Some interaction between hypertension and smoking was found to be synergistic. When hypertension and smoking co-existed, the all-cause mortality outcome [relative risk (RR) = 4.25] was larger than the sum or product of each individual risk for hypertension (RR = 2.16) or for smoking (RR = 1.97). The excess mortality risks of smoking for smokers were converted into a 'blood pressure equivalence'. The results demonstrate that the addition of smoking was similar to an increase of mortality risk approximately equivalent to an increase in blood pressure of 40 mmHg. CONCLUSIONS: Smoking cessation in hypertensive patients could provide a reduction of mortality risks similar to a permanent reduction of 40 mmHg in blood pressure, over and above any antihypertensive medications. Appreciating this relationship enables physicians to bridge the clinical disconnection and motivates hypertensive smokers to seek smoking cessation. The use of a 'blood pressure equivalence of smoking' can link the two separate risk factors and may lead to a paradigm shift in overcoming an existing clinical challenge.

A 10-year experience with universal health insurance in Taiwan: measuring changes in health and health disparity.

BACKGROUND: Universal national health insurance, financed jointly by payroll taxes, subsidies, and individual premiums, commenced in Taiwan in 1995. Coverage expanded from 57% of the population (before the introduction of national health insurance) to 98%. OBJECTIVE: To assess the role of national health insurance in improving life expectancy and reducing health disparities in Taiwan. DESIGN: A before-and-after comparison of the decade before the introduction of national health insurance (1982-1984 to 1992-1994) with the decade after (1992-1994 to 2002-2004). SETTING: Taiwan. PATIENTS: All townships (n = 358) in Taiwan were ranked according to overall mortality rates before the introduction of national health insurance and then ranked into 10 health class groups in descending order of health (groups 1 [healthiest] to 10 [least healthy]). MEASUREMENTS: Health improvement (change in life expectancy after the introduction of national health insurance) and health disparity (reduction in the difference in life expectancy between the highest- and lowest-ranked health class groups). RESULTS: After the introduction of national health insurance, life expectancy increased more in health class groups that had higher mortality rates before the introduction of national health insurance and health disparity narrowed, reversing an earlier trend toward widening disparity. The major contributors to the reduction in disparity were relatively larger reductions in death from cardiovascular diseases, ill-defined conditions, infectious diseases, and accidents in the lower-ranked health class groups. However, death from cancer increased more in the lower-ranked health class groups. Utilization of medical services increased, whereas cost remained at 5% to 6% of the gross domestic product. The per capita average annual number of visits to the physician's office was 14. LIMITATION: The interpretation of comparisons before and after the introduction of national health insurance assumes that the changes were entirely due to the effect of national health insurance rather than secular trends. CONCLUSION: Life expectancy after the introduction of national health insurance improved more for lower-ranked health classes, resulting in narrowed health disparity. The magnitude of the reduced disparity was small compared with the size of the remaining gaps. Relying on universal insurance alone to eliminate health disparity does not seem realistic. To further reduce health disparity, universal insurance programs should incorporate primary prevention, focusing on lifestyle risk reductions.

Increased mortality risks of pre-diabetes (impaired fasting glucose) in Taiwan.

OBJECTIVE: The objective of this article was to assess mortality risks at different levels of fasting blood glucose (FBG) in Taiwan, with particular attention to those pre-diabetic subjects with impaired fasting glucose (IFG). RESEARCH DESIGN AND METHODS: Governmental employees and schoolteachers were followed up for an average of 11 years. With the use of Cox regression analyses, mortality risks were calculated for 36,386 subjects, aged 40-69. RESULTS: FBG > or =110 mg/dl was associated with increased mortality risks for all causes, cardiovascular diseases (CVD), and diabetes. IFG, when defined as 110-125 mg/dl, was associated with a significant increase for CVD and/or diabetes mortality. These mortality risks remained elevated when known CVD risk factors were adjusted for. The IFG group shared risk factor characteristics more with the FBG > or =126 mg/dl group than with the FBG <110 mg/dl group. When IFG was defined as 100-125 mg/dl, the number of subjects quadrupled, but mortality risks diminished substantially because of the inclusion of 100-109 mg/dl group. The lowest FBG group, 50-75 mg/dl, had a significant 2-fold risk from all causes. CONCLUSIONS: There was an overall J-shaped relationship between all-cause mortality and FBG. IFG, when defined as 110-125 mg/dl, is an independent risk factor and should be aggressively treated as a disease because its subsequent mortality risks for CVD and diabetes were significantly increased. The newly defined IFG at 100-125 mg/dl did not have the predictive power for later increases in CVD or diabetes mortality.