Mortality risk in patients with preserved ratio impaired spirometry: assessing the role of physical activity.

BACKGROUND: While all-cause mortality is reportedly increased in preserved ratio impaired spirometry (PRISm), no remedial efforts have been suggested. AIM: To study the ability of physical activity (PA) on reducing the morality increased in PRISm patients. DESIGN: We prospectively enrolled a cohort of Taiwanese adults from 1994 to 2018 in a health surveillance program. METHODS: Mortality risks of those who were inactive were compared against those meeting the current recommendation of 150 min/week of physical activity. Cox proportional hazards models were used for hazard ratios and life table method was for estimating loss of life expectancy. RESULTS: A total of 461,183 adults was enrolled. Among them, one seventh of the cohort (65,832 or 14.3%) had PRISm, and 53.1% were inactive. Those who were inactive with PRISm had 28% increased mortality from all-cause, 45% from cardiovascular diseases and 67% from respiratory disease, with a 3-year reduction in life expectancy (males, 3.72 and females, 2.93). In PRISm patients who met the exercise recommendation, excess mortality was reduced by 2/3, both all-cause (from 28% to 9%) and CVD (from 45% to 15%). CONCLUSION: PRISm involves a large portion of general population (14.3%) and shortens life expectancy by 3 years. More than half of the subjects were physically inactive, and adherence to 150 min/week of physical activity was associated with a two-third reduction of excess mortality from all cause and from CVD. Recommending physical activity among those with PRISm might be highly beneficial, although exercise alone may not eliminate all risks associated with PRISm.

Uncovering a dose-response relationship between positive fecal immunochemical test (FIT) and all-cause, cardiovascular and cancer-related mortality.

BACKGROUND: Fecal immunochemical test (FIT) is for colorectal cancer (CRC) screening. Its association with non-CRC mortality has been overlooked. Given the quantitative FIT values, its dose-response relationships with different causes of deaths and years of life shortened were assessed. METHODS: This retrospective study included 546,214 adults aged ≥ 20 who attended a health surveillance program from 1994 to 2017 and were followed up until the end of 2020. FIT ≥ 20 µg Hb/g was defined as positive. The Cox model was used to assess adjusted hazard ratios (aHR). RESULTS: Positive FIT was associated with increased all-cause mortality (aHR: 1.34, 95 % CI: 1.25-1.44) and all-cancer mortality (aHR: 1.71, 95 % CI: 1.55-1.89), with a reduction of life expectancy by 4 years. The association remained even with CRC excluded. With each 10 µg Hb/g increase in FIT above 20 µg Hb/g, life expectancy was reduced by one year, and mortality increased by 4 %. About 18.6 % of deaths with positive FIT were attributed to cardiovascular disease (CVD), followed by CRC (13.5 %) and upper gastrointestinal (GI) cancers (4.5 %). The all-cause mortality rate after excluding CRC for positive FIT was 3.56/1,000 person-year, comparable to the all-cause mortality rate of 3.69/1,000 person-year for hypertension. CONCLUSION: Positive FIT was associated with increased mortality in a dose-response manner and shortened life expectancy by 4 years, an overlooked risk comparable to hypertension, even with CRC excluded. After a negative colonoscopy, subjects with positive FIT should undergo a workup on CVD risk factors and look for other upper GI cancers.

Association of Sugar-Sweetened Beverages and Cardiovascular Diseases Mortality in a Large Young Cohort of Nearly 300,000 Adults (Age 20-39).

(1) Background: The association of sugar-sweetened beverages (SSBs) with cardiovascular disease (CVD) mortality in younger adults (age 20−39) is rarely mentioned in the literature. Younger adults are less vulnerable to CVDs, but they tend to consume more SSBs. This prospective study aimed to assess the association between CVD mortality and SSBs in younger adults between 1994 and 2017. (2) Methods: The cohort enrolled 288,747 participants consisting of 139,413 men and 148,355 women, with a mean age 30.6 ± 4.8 years, from a health surveillance program. SSBs referred to any drink with real sugar added, such as fructose corn syrup or sucrose. One serving of SSB contains about 150 Kcal of sugar in 12 oz of drink. Cox models were used to estimate the mortality risk. (3) Results: There were 391 deaths from CVDs in the younger adults, and the positive association with CVD mortality started when SSB intake was ≥2 servings/day (HR: 1.59, 95% CI: 1.16−2.17). With mortalities from diabetes and kidney disease added to CVDs, the so-called expanded CVD mortality risk was 1.49 (95% CI: 1.11−2.01). By excluding CVD risk factors (hypertension, diabetes, and smoking), the CVD mortality risk increased to 2.48 (95% CI: 1.33−4.62). The dose−response relationship persisted (p < 0.05 for trend) in every model above. (4) Conclusions: Higher intake of SSBs (≥2 servings/day) was associated with increased CVD mortality in younger adults. The younger adults (age 20−39) with SSB intake ≥2 servings/day had a 50% increase in CVD mortality in our study, and the mortality risk increased up to 2.5 times for those without CVD risk factors. The dose−response relationship between the quantity of SSB intake and the mortality risk of CVD in younger adults discourages SSB intake for the prevention of CVD mortality.

The effects of modest drinking on life expectancy and mortality risks: a population-based cohort study.

Modest drinking has been repeatedly discussed in scientific papers as protective against certain diseases, such as cardiovascular diseases, but in most cases, alcohol worsens health conditions, especially when consumed at high risk levels. The complexity of the risk relationship between alcohol and health conditions has confused clinicians as to whether it should be recommended. The study aims to balance the risks and benefits of modest drinking. This retrospective cohort study of 430,016 adults recruited from a standard health-screening program since 1994, with 11,031 deaths identified as of 2008. Drinking distinguished "modest drinker" (no more than one drink a day) from "regular drinker". Mortality risks including all-cause mortality and diseases-specific mortality with hazard ratio (HR) were calculated by adjusting for 15 confounders. Life table was used for life expectancy. Risk predictors were subjected to Cox proportional hazards regression analysis to identify significant predictors in multivariate models and life expectancy analysis. Nearly one out of 4 males (23%) was a modest drinker, who gained 0.94 year (95% CI 0.65-1.23 year) in life over non-drinker and had 8% reduction in adjusted all-cause mortality (HR 0.92, 95% CI 0.86-0.97). In contrast, regular drinkers had 43% increase in overall mortality (HR 1.43, CI 1.35-1.52) and shortened life by 6.9 years (95% CI 6.6-7.1 years). As most drinkers also smoked, 59% in modest and 75% in regular, the combined effect shortened life by 2.0 years (95% CI 1.6-2.4 years) in modest drinker and 10.3 years (95% CI 9.8-10.7 years) in regular drinker. Cancer were increased in modest drinkers for oral (HR 2.35, CI 1.38-4.01) and esophageal (HR 3.83, CI 1.90-7.73) cancer. The gain of one year by modest drinkers was erased by a two to fourfold increase in oral and esophageal cancer and that drinking beyond modest amount led to a large loss of life expectancy. Given that drinkers are prone to cross the line of drinking, clinicians should balance the risks and benefits of drinking, as well as the understanding of whether the patient is at risk for addiction.

"Sugar-Sweetened Beverages" Is an Independent Risk From Pancreatic Cancer: Based on Half a Million Asian Cohort Followed for 25 Years.

Although the link between sugar-sweetened beverages (SSB) and pancreatic cancer has been suggested for its insulin-stimulating connection, most epidemiological studies showed inconclusive relationship. Whether the result was limited by sample size is explored. This prospective study followed 491,929 adults, consisting of 235,427 men and 256,502 women (mean age: 39.9, standard deviation: 13.2), from a health surveillance program and there were 523 pancreatic cancer deaths between 1994 and 2017. The individual identification numbers of the cohort were matched with the National Death file for mortality, and Cox models were used to assess the risk. The amount of SSB intake was recorded based on the average consumption in the month before interview by a structured questionnaire. We classified the amount of SSB intake into 4 categories: 0-<0.5 serving/day, ≥0.5-<1 serving per day, ≥1-<2 servings per day, and ≥2 servings per day. One serving was defined as equivalent to 12 oz and contained 35 g added sugar. We used the age and the variables at cohort enrolment as the reported risks of pancreatic cancers. The cohort was divided into 3 age groups, 20-39, 40-59, and ≥60. We found young people (age <40) had higher prevalence and frequency of sugar-sweetened beverages than the elderly. Those consuming 2 servings/day had a 50% increase in pancreatic cancer mortality (HR = 1.55, 95% CI: 1.08-2.24) for the total cohort, but a 3-fold increase (HR: 3.09, 95% CI: 1.44-6.62) for the young. The risk started at 1 serving every other day, with a dose-response relationship. The association of SSB intake of ≥2 servings/day with pancreatic cancer mortality among the total cohort remained significant after excluding those who smoke or have diabetes (HR: 2.12, 97% CI: 1.26-3.57), are obese (HR: 1.57, 95% CI: 1.08-2.30), have hypertension (HR: 1.90, 95% CI: 1.20-3.00), or excluding who died within 3 years after enrollment (HR: 1.67, 95% CI: 1.15-2.45). Risks remained in the sensitivity analyses, implying its independent nature. We concluded that frequent drinking of SSB increased pancreatic cancer in adults, with highest risk among young people.

The ability of physical activity in reducing mortality risks and cardiovascular loading and in extending life expectancy in patients with COPD.

For chronic obstructive pulmonary disease (COPD), the role of physical activity in reducing COPD mortality and heart loading and in extending life expectancy remains unclear. Participants in comprehensive medical screening were recruited with spirometry on everyone. We analyzed physical activity volume calculated from intensity, duration and frequency of self-reported exercise history. Deaths were identified from the National Death File. The impacts of physical activity on mortality, heart rate and life expectancy were analyzed. Among the cohort of 483,603 adults, 32,535 had spirometry-determined COPD, indicating an adjusted national prevalence of 11.4% (male) and 9.8% (female). On the average, COPD increased all-cause mortality with a hazard ratio of 1.44 and loss of 6.0 years in life expectancy. Almost two thirds (65%) of the causes of deaths were extra-pulmonary, such as cardiovascular disease, diabetes, cancer and kidney diseases. In addition, COPD was associated with increases in heart rate proportionate to its severity, which led to higher mortality. Participants with COPD who were fully active physically could reduce mortality and have improved heart rates as compared with those without physical activity. In addition, their life expectancy could be extended close to those of the no COPD but inactive cohort. Fully active physical activity can help patients with COPD overcome most of the mortality risks, decrease heart rate, and achieve a life expectancy close to that of patients without COPD. The effectiveness of physical activity on COPD is facilitated by its systemic nature beyond lung disease.

Smoking and nasopharyngeal cancer: individual data meta-analysis of six prospective studies on 334 935 men.

BACKGROUND: The role of smoking in nasopharyngeal carcinoma (NPC) remains uncertain, especially in endemic regions. We conducted an individual participant data (IPD) meta-analysis of prospective cohort studies to investigate the associations between smoking exposure and risk of NPC. METHODS: We obtained individual participant data of 334 935 male participants from six eligible population-based cohorts in NPC-endemic regions, including two each in Guangzhou and Taiwan, and one each in Hong Kong and Singapore. We used one- and two-stage approaches IPD meta-analysis and Cox proportional hazard models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) of NPC for smoking exposure adjusting for age and drinking status. RESULTS: During 2 961 315 person-years of follow-up, 399 NPC evens were ascertained. Risks of NPC were higher in ever versus never smokers (HRone-stage = 1.32, 95% CI = 1.07-1.63, P = 0.0088; HRtwo-stage = 1.27, 1.01-1.60, 0.04). These positive associations appeared to be stronger in ever smokers who consumed 16+ cigarettes/day (HRone-stage = 1.67, 95% CI = 1.29-2.16, P = 0.0001), and in those who started smoking at age younger than 16 (2.16, 1.33-3.50, 0.0103), with dose-response relationships (P-values for trend = 0.0028 and 0.0103, respectively). Quitting (versus daily smoking) showed a small reduced risk (stopped for 5+ years: HRone-stage = 0.91, 95% CI = 0.60-1.39, P = 0.66; for former smokers: HRtwo-stage = 0.84, 0.61-1.14, 0.26). CONCLUSIONS: This first IPD meta-analysis from six prospective cohorts in endemic regions has provided robust observational evidence that smoking increased NPC risk in men. NPC should be added to the 12-16 cancer sites known to be tobacco-related cancers. Strong tobacco control policies, preventing young individuals from smoking, would reduce NPC risk in endemic regions.

Low-Density Lipoprotein Cholesterol and Mortality in Patients With Intracerebral Hemorrhage in Taiwan.

Objective: Lower serum low-density lipoprotein cholesterol (LDL-C) levels are associated with increased intracerebral hemorrhage (ICH) risk. However, reverse causality and residual confounding has not attracted public attention. Therefore, we assessed whether people with LDL-C have increased risk of mortality adjusting for potential confounders using two large Taiwan cohorts. Methods: The Mei-Jhao (MJ) cohort has 414,372 adults participating in a medical screening program with 378 ICH deaths within 15 years of follow-up (1994-2008). Cox proportional hazards regressions estimated hazard death ratios according to LDL-C levels. We identified 4,606 ICH patients from the Taiwan Stroke Registry (TSR) and analyzed the impact of LDL-C on 3-month mortality. Results: Low cholesterol (LDL-C <100 mg/dL), found in 1/4 of the MJ cohort, was highly prevalent (36%) among young adults (age 20-39). There was a graded relationship between cholesterol and mortality for ICH [Hazard ratio, 1.56; 95% confidence interval (CI), 1.13-2.16]. Compared with patients with an LDL-C of 110-129 mg/dL in TSR, the risk for mortality was 1.84 (95% CI, 1.28-2.63) with an LDL-C of <100 mg/dL. Conclusion: Lower serum LDL-C level independently predicts higher mortality after acute ICH. While its causative role may vary, low cholesterol may pose potential harms in Taiwan.

A novel cardiovascular death prediction model for Chinese individuals: A prospective cohort study of 381,963 study participants.

BACKGROUND AND AIMS: We aimed at developing a novel risk prediction model for death from cardiovascular disease (CVD) for Chinese individuals, based upon a large cohort from Taiwan. METHODS: This Chinese cohort came from Taiwan, with 381,963 individuals free from CVD, recruited from a private health surveillance program. With a median follow-up of 8.8 years, 1894 CVD deaths out of a total of 10,829 deaths were identified by linking cohort ID with the National Death File. RESULTS: A novel CVD death risk prediction model for Chinese individuals was established from this cohort. An increase in the resting heart rate was the statistically independent predictor in this model. The discriminatory accuracy was measured by generating the receiver operating characteristic (ROC) curve, and the area under the ROC curve was 0.913 (95% CI = 0.907 to 0.920). CONCLUSIONS: A novel cardiovascular death prediction model with high predictability for Chinese individuals was demonstrated in the present study.

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.

The Role of Physical Activity in Harm Reduction among Betel Quid Chewers from a Prospective Cohort of 419,378 Individuals.

OBJECTIVE: To assess the benefits of regular exercise in reducing harms associated with betel quid (BQ) chewing. METHODS: The study cohort, 419,378 individuals, participated in a medical screening program between 1994 and 2008, with 38,324 male and 1,495 female chewers, who consumed 5-15 quids of BQ a day. Physical activity of each individual, based on "MET-hour/week", was classified as "inactive" or "active", where activity started from a daily 15 minutes/day or more of brisk walking (≥3.75 MET-hour/week). Hazard ratios for mortality and remaining years in life expectancy were calculated. RESULTS: Nearly one fifth (18.7%) of men, but only 0.7% of women were chewers. Chewers had a 10-fold increase in oral cancer risk; and a 2-3-fold increase in mortality from lung, esophagus and liver cancer, cardiovascular disease, and diabetes, with doubling of all-cause mortality. More than half of chewers were physically inactive (59%). Physical activity was beneficial for chewers, with a reduction of all-cause mortality by 19%. Inactive chewers had their lifespan shortened by 6.3 years, compared to non-chewers, but being active, chewers improved their health by gaining 2.5 years. The improvement, however, fell short of offsetting the harms from chewing. CONCLUSIONS: Chewers had serious health consequences, but being physically active, chewers could mitigate some of these adverse effects, and extend life expectancy by 2.5 years and reduce mortality by one fifth. Encouraging exercise, in addition to quitting chewing, remains the best advice for 1.5 million chewers in Taiwan.

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.

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.