Impact of overweight and obesity on the risk of hepatocellular carcinoma: a prospective cohort study in 14.3 million Koreans.

BACKGROUND: Whether obesity and being overweight, defined by body mass index (BMI), increase hepatocellular carcinoma (HCC) has been less apparent in Asian populations. METHODS: Overall, 14,265,822 Korean adults who underwent routine health examinations during 2003-2006 were followed up for HCC. Multivariable-adjusted hazard ratios (HRs) associated with BMI were calculated. RESULTS: During 13.7 years (mean) of follow-up, 47,308 individuals developed HCC. HRs of HCC associated with BMIs of 25.0-26.4, 26.5-27.9, 28.0-29.4, 29.5-30.9 and ≥31 kg/m² compared to those for 23.5-24.9 kg/m² were 1.05, 1.20, 1.39, 1.59 and 2.13, respectively. For BMI < 25 kg/m², linear associations were not apparent. For BMI ≥ 25 kg/m2, the HR per 5 kg/m2 increase in BMI was 1.60 (total), 1.60 (men), and 1.59 (women). The corresponding HRs were 1.56, 1.61 and 1.60 for individuals aged <45, 45-64 and ≥65 years, respectively. Further adjustment for alanine transaminase (ALT) levels substantially reduced the HRs for high BMI, especially in men and younger adults. CONCLUSIONS: Overweight and obesity clearly increase HCC risk in Koreans. ALT levels are a mediator of the impact of obesity, but it may not accurately predict high BMI-induced liver damage that can potentially progress to HCC, especially in women and older adults.

Associations between the triglyceride-glucose index and cardiovascular disease in over 150,000 cancer survivors: a population-based cohort study.

BACKGROUND: The prevention of subsequent cardiovascular disease (CVD) is an essential part of cancer survivorship care. We conducted the present study to investigate the association between the TyG index (a surrogate marker of insulin resistance) and the risk of cardiovascular disease (CVD) events in cancer survivors. METHODS: Adult cancer patients, who underwent routine health examinations during 2009-2010 and were survived for more than 5 years as of January 1, 2011, were followed for hospitalization of CVD (either ischemic heart disease, stroke, or heart failure) until December 2020. Cox model was used to calculate hazard ratios associated with baseline TyG index (loge [fasting triglyceride (mg) × fasting glucose (mg)/2]) for the CVD hospitalization. RESULTS: A total of 155,167 cancer survivors (mean age 59.9 ± 12.0 years, female 59.1%) were included in this study. A graded positive association was observed between TyG and CVD hospitalization. An 8% elevated risk for CVD hospitalization was observed for a TyG index of 8-8.4 (aHR 1.08 [95% CI 1.01-1.14]); 10% elevated risk for a TyG index of 8.5-8.9 (aHR 1.10 [95% CI 1.03-1.17]); 23% elevated risk for a TyG index of 9.0-9.4 (aHR 1.23 [95% CI 1.15-1.31]); 34% elevated risk for a TyG index of 9.5-9.9 (aHR 1.34 [95% CI 1.23-1.47]); and 55% elevated risk for a TyG index ≥ 10 compared to the reference group (TyG index < 8). Per 1-unit increase in the TyG index, a 16% increase in CVD hospitalization and a 45% increase in acute myocardial infarction hospitalization were demonstrated. Graded positive associations were evident for atherosclerotic CVD subtypes, such as ischemic heart disease, acute myocardial infarction, and ischemic stroke, but not for hemorrhagic stroke or heart failure. CONCLUSIONS: The TyG index may serve as a simple surrogate marker for the risk stratification of future CVD events, particularly atherosclerotic subtypes, in cancer survivors.

Complex interaction of fasting glucose, body mass index, age and sex on all-cause mortality: a cohort study in 15 million Korean adults.

AIMS/HYPOTHESIS: The aim of this work was to examine whether synergistic associations with mortality exist for BMI and fasting blood glucose (FBG) and to identify FBG-BMI combined subgroups with higher mortality according to sex and age. METHODS: A total of 15,149,275 Korean adults participated in health examinations during 2003-2006 and were followed up until December 2018. Mortality HRs of 40 FBG-BMI combined groups were assessed by Cox proportional hazards models. RESULTS: During a mean 13.7 years of follow-up, 1,213,401 individuals died. A J-shaped association was seen between FBG and all-cause mortality for all BMI categories. Those with BMI <20 kg/m2 had the highest mortality for any given FBG level, followed by those with BMI 20-22.4 kg/m2. The detrimental effect of elevated FBG was greater among leaner individuals than more corpulent individuals. Moreover, the synergistic adverse effects of hyperglycaemia and leanness was stronger in younger adults than in older adults. Compared with the reference group (overweight with normoglycaemia), age- and sex-adjusted HRs of the leanest with normoglycaemia (BMI <20 kg/m2 and FBG 4.4-5.2 mmol/l), overweight with diabetes (BMI 25-27.4 kg/m2 and FBG ≥10.0 mmol/l) and leanest with diabetes (BMI <20 kg/m2 and FBG ≥10.0 mmol/l) were 1.29, 2.59 and 11.18, respectively, in those aged 18-44 years and 1.56, 1.72 and 2.87, respectively, in those aged 75-99 years. The identification of BMI-FBG subgroups associated with higher mortality was not straightforward, illustrated by the group with FBG 6.1-6.9 mmol/l and BMI 20-22.4 kg/m2 having a similar or higher mortality compared with the group with FBG 7.0-9.9 mmol/l and BMI ≥22.5 kg/m2. In women aged <45 years with FBG <6.9 mmol/l, those with BMI ≥27.5 kg/m2 had the highest mortality, whereas individuals with BMI <20 kg/m2 had the highest mortality for each given FBG level in other age and sex groups. CONCLUSIONS/INTERPRETATION: Leanness and hyperglycaemia interact together to increase mortality in a supra-multiplicative manner, especially in younger adults; the interactions of BMI, FBG, sex and age with mortality are complex. Graphical abstract.

Higher cholesterol levels, not statin use, are associated with a lower risk of hepatocellular carcinoma.

We aimed to examine whether statin users have a lower risk of hepatocellular carcinoma (HCC) after careful consideration of prevalent statin use and cholesterol levels. During a mean prospective follow-up of 8.4 years in 400,318 Koreans, 1686 individuals were diagnosed with HCC. When prevalent users were included, HCC risk was reduced by >50% in statin users, regardless of adjustment for total cholesterol (TC). When prevalent users were excluded, new users who initiated statins within 6 months after baseline had a 40% lower risk of HCC (hazard ratio [HR] = 0.59) in a TC-unadjusted analysis. However, this relationship disappeared (HR = 1.16, 95% CI = 0.80-1.69) after adjusting for TC levels measured within 6 months before statin initiation. TC levels had strong inverse associations with HCC in each model. High cholesterol levels at statin initiation, not statin use, were associated with reduced risk of HCC. Our study suggests no protective effect of statins against HCC.

Body mass index and the risk of acute pancreatitis by etiology: A prospective analysis of Korean National Screening Cohort.

BACKGROUND: It is unclear whether obesity increases the incidence of acute pancreatitis (AP) in the general population. Further, no study has prospectively examined the associations of the risk of AP by etiology with measured body mass index (BMI) values. METHODS: A total of 512 928 Korean participants in routine health examinations during 2002-2003 were followed up until 2013 via linkage to national hospital discharge records to assess AP incidence. Multivariable-adjusted hazard ratios were calculated using BMI measurements. RESULTS: During 10.5 mean years of follow-up, 1656 persons developed AP (337 gallstone related and 1319 non-gallstone related). Nonlinear associations were found: U-curves for total and non-gallstone-related AP and a reverse L-curve for gallstone-related AP. Each 5 kg/m2 increment in BMI increased gallstone-related AP by 123% (95% confidence interval = 48-234%) and non-gallstone-related AP by 42% (9-84%) in the range ≥ 25 kg/m2 (Pheterogeneity  = 0.068). Obese persons had a doubled risk of gallstone-related AP compared with normal-weight persons. In the range < 25 kg/m2 , BMI had inverse association with non-gallstone-related AP but no association with gallstone-related AP (Pheterogeneity  < 0.001). In subgroup analyses, for non-gallstone-related AP, hazard ratios per each 5 kg/m2 BMI increment were 0.50 (men), 0.73 (women), 0.46 (alcohol drinkers), 0.69 (alcohol non-drinkers), 0.43 (ever smokers), and 0.73 (never smokers). CONCLUSIONS: Gallstone-related AP and non-gallstone-related AP have different nonlinear associations with BMI. Higher BMI increases the risk of both gallstone-related AP and non-gallstone-related AP but more strongly for gallstone-related AP. For non-gallstone-related AP, in the range < 25 kg/m2 , BMI has inverse associations that were stronger in men, current alcohol drinkers, and ever smokers than in their counterparts.

Risk factors for hepatocellular carcinoma by age, sex, and liver disorder status: A prospective cohort study in Korea.

BACKGROUND: To the authors' knowledge, relatively little is known regarding the interaction of risk factors for hepatocellular carcinoma (HCC) with age, sex, and liver disorder status. METHODS: The authors followed 504,646 Korean patients aged 40 to 80 years who underwent routine health checkups between 2002 and 2003 until 2013 via linkage to national hospital discharge records. RESULTS: HCC occurred in 2744 individuals. In the sex-adjusted and age-adjusted analysis, cirrhosis increased the incidence of HCC by 42-fold, followed by hepatitis B virus (21-fold), hepatitis C virus (HCV; 19-fold), male sex (4.3-fold), and each 5-year age increment (1.24-fold). In the multivariable adjusted analysis, diabetes increased the risk of HCC by 80%, alcohol consumption ≥80 g/day increased the risk by 75%, alcohol consumption of 40 to 79 g/day increased the risk by 37%, and being a current smoker increased the risk by 25%. The multivariable adjusted hazard ratios of male sex and HCV were 6.27 and 5.72, respectively, at age <50 years, but were 2.09 and 22.51, respectively, at age ≥70 years. Each 20 g/day of alcohol consumption increased the risk of HCC by 6% (P = .11), 8% (P = .02), 16% (P<.001), and 30% (P<.001), respectively, in individuals aged <50 years, 50 to 59 years, 60 to 69 years, and 70 to 80 years. In individuals without a liver disorder, body mass index was found to be positively associated with HCC, whereas patients with a liver disorder demonstrated an inverse association. Women had higher adjusted hazard ratios associated with age and cirrhosis compared with men. CONCLUSIONS: With advancing age, the effects of alcohol use and HCV on the development of HCC become stronger, whereas the effect of male sex weakens. Lifetime moderate alcohol consumption may cause HCC in the elderly. Smoking increases the risk of HCC irrespective of viral hepatitis, and diabetes increases the risk of HCC independent of cirrhosis. Cancer 2018;124:2748-2757. © 2018 American Cancer Society.

Body mass index and gastrointestinal cancer mortality in Korean adults: A prospective cohort study.

BACKGROUND: The association between body mass index (BMI) and mortality from gastrointestinal (GI) cancer remains unclear, especially in Asian populations. METHODS: A total of 510 148 Korean adults who participated in routine health examinations during the period 2002-2003 were followed up until 2013. RESULTS: During a mean follow up of 10.5 years, 7831 individuals died of GI cancer. Various associations with BMI were found: U-curve (overall GI, colorectal, liver, and gallbladder cancer), L-curve (stomach cancer), linear (esophageal, extrahepatic bile duct [EBD], and small intestine cancer), and none (pancreatic cancer). Overall GI cancer mortality was lowest at approximately 23.5-26 kg/m2 . For cancers with linear associations, the multivariable adjusted hazard ratios per each 5 kg/m2 higher BMI were 0.53 (95% confidence interval = 0.43-0.65, esophagus), 1.19 (1.02-1.40, EBD), and 0.64 (0.41-0.999, small intestine). For cancers with U-curve or L-curve associations, the corresponding hazard ratios ≥25 kg/m2 were 1.19 (1.08-1.32, overall GI), 1.30 (1.04-1.64, colorectal), 1.28 (1.07-1.53, liver), and 1.30 (0.85-1.97, gallbladder), while in the range of <25 kg/m2 , they were 0.81 (0.76-0.87, overall GI), 0.43 (0.32-0.58, esophagus), 0.70 (0.62-0.79, stomach), and 0.77 (0.65-0.90, colorectal), and these inverse associations did not weaken after excluding the first 7 years of follow up and ever smokers. CONCLUSIONS: Both low and high BMIs were associated with excess mortality from GI cancers in Korean adults. EBD cancer had a positive association, while esophageal and small intestine cancers had inverse associations. Above 25 kg/m2 , liver and colorectal cancers had positive associations with BMI, whereas below 25 kg/m2 , stomach and colorectal cancers had inverse associations.

Low Systolic Blood Pressure and Vascular Mortality Among More Than 1 Million Korean Adults.

BACKGROUND: The association between low systolic blood pressure (SBP) and vascular disease is unclear, especially in nonclinical populations. METHODS AND RESULTS: We studied 1 235 246 individuals who participated in routine medical examinations between 1992 and 1995. The hazard ratios (HRs) were adjusted for potential confounders. During 22.7 million person-years of follow-up, 34 816 individuals died of atherosclerotic vascular diseases. An increase in SBP was directly related to an increase in vascular mortality at SBP above ≈100 mmHg. The group with the lowest SBP (<90 mm Hg) had a higher HR for mortality from atherosclerotic vascular disease (HR, 1.53; 95% confidence interval, 1.15-2.03) in comparison with those with an SBP of 90 to 99 mm Hg. The HR associated with the lowest SBP was 2.54 (95% confidence interval, 1.51-4.29) for ischemic heart disease and 1.21 (95% confidence interval, 0.79-1.85) for stroke. Regarding stroke subtype, mortality from hemorrhagic stroke (HR per 10 mm Hg increase, 0.53; 95% confidence interval, 0.29-0.96), rather than mortality from ischemic stroke (HR per 10 mm Hg increase, 1.00; 95% confidence interval, 0.51-1.97), was inversely associated with SBP when SBP fell to <100 mm Hg. Even when excluding the first 5 years of follow-up, the HRs associated with the lowest SBP did not decrease. The inverse association between SBP and vascular mortality in the range <100 mm Hg tended to be apparent in people aged 60 to 95 years in comparison with individuals aged 30 to 59 years. CONCLUSIONS: J-curve associations exist between SBP and vascular mortality, which reach a nadir at ≈100 mm Hg. SBP of <90 mm Hg may portend death from vascular disease, particularly from ischemic heart disease.

Agent Orange exposure and disease prevalence in Korean Vietnam veterans: the Korean veterans health study.

Between 1961 and 1971, military herbicides were used by the United States and allied forces for military purposes. Agent Orange, the most-used herbicide, was a mixture of 2,4-dichlorophenoxyacetic acid (2,4-D) and 2,4,5-trichlorophenoxyacetic acid, and contained an impurity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Many Korean Vietnam veterans were exposed to Agent Orange during the Vietnam War. The aim of this study was to evaluate the association between Agent Orange exposure and the prevalence of diseases of the endocrine, nervous, circulatory, respiratory, and digestive systems. The Agent Orange exposure was assessed by a geographic information system-based model. A total of 111,726 Korean Vietnam veterans were analyzed for prevalence using the Korea National Health Insurance claims data from January 2000 to September 2005. After adjusting for covariates, the high exposure group had modestly elevated odds ratios (ORs) for endocrine diseases combined and neurologic diseases combined. The adjusted ORs were significantly higher in the high exposure group than in the low exposure group for hypothyroidism (OR=1.13), autoimmune thyroiditis (OR=1.93), diabetes mellitus (OR=1.04), other endocrine gland disorders including pituitary gland disorders (OR=1.43), amyloidosis (OR=3.02), systemic atrophies affecting the nervous system including spinal muscular atrophy (OR=1.27), Alzheimer disease (OR=1.64), peripheral polyneuropathies (OR=1.09), angina pectoris (OR=1.04), stroke (OR=1.09), chronic obstructive pulmonary diseases (COPD) including chronic bronchitis (OR=1.05) and bronchiectasis (OR=1.16), asthma (OR=1.04), peptic ulcer (OR=1.03), and liver cirrhosis (OR=1.08). In conclusion, Agent Orange exposure increased the prevalence of endocrine disorders, especially in the thyroid and pituitary gland; various neurologic diseases; COPD; and liver cirrhosis. Overall, this study suggests that Agent Orange/2,4-D/TCDD exposure several decades earlier may increase morbidity from various diseases, some of which have rarely been explored in previous epidemiologic studies.

Impact of hypertriglyceridaemia on cardiovascular mortality according to low-density lipoprotein cholesterol in a 15.6-million population.

AIMS: The aim of this study was to assess the association between triglyceride (TG) levels and cardiovascular disease (CVD) mortality concerning low-density lipoprotein cholesterol (LDL-C) and age in the general population. METHODS AND RESULTS: From the Korean National Health Insurance Service database, 15 672 028 participants aged 18-99 who underwent routine health examinations were followed up for CVD mortality. Hazard ratios for CVD mortality were calculated using Cox models after adjusting for various confounders. During a mean of 8.8 years of follow-up, 105 174 individuals died of CVD. There was a clear log-linear association between TG and overall CVD mortality down to 50 mg/dL. Each two-fold increase in TG was associated with 1.10-fold (overall CVD), 1.22-fold [ischaemic heart disease (IHD)], 1.24-fold [acute myocardial infarction (AMI)], and 1.10-fold (ischaemic stroke) higher CVD mortality. Haemorrhagic stroke and heart failure were not associated with TG levels. The impact of hypertriglyceridaemia (HTG) on CVD weakened but remained present in persons with LDL-C < 100 mg/dL, in whom each two-fold higher TG was associated with 1.05-fold (overall CVD), 1.12-fold (IHD), 1.15-fold (AMI), and 1.05-fold (ischaemic stroke) higher CVD mortality. The younger population (18-44 years) had stronger associations between TG levels and mortality from overall CVD, IHD, and AMI than the older population. CONCLUSION: Hypertriglyceridaemia independently raises CVD mortality with lingering risks in young and older individuals with low LDL-C levels, suggesting the importance of management of HTG even with controlled LDL-C.

This prospective study evaluated the association between triglyceride (TG) levels and cardiovascular disease (CVD) mortality in the general population, particularly in individuals with well-controlled low-density lipoprotein cholesterol (LDL-C) levels. The TG levels log-linearly increased the mortality from CVD, especially ischaemic heart disease and ischaemic stroke, down to at least 50 mg/dL (0.56 mmol/L), as residual CVD risks associated with high TG were apparent in individuals, even with LDL-C < 100 mg/dL (2.59 mmol/L). Maintaining TG levels below 100 mg/dL may be beneficial even in seemingly low-risk groups, such as young people with normal or optimal LDL-C levels.

Socioeconomic status and cardiovascular mortality in over 170,000 cancer survivors.

AIMS: Cardiovascular health is acknowledged as a crucial concern among cancer survivors. Socioeconomic status (SES) is an essential but often neglected risk factor for cardiovascular disease (CVD). We conducted this study to identify the relationship between SES and CVD mortality in cancer survivors. METHODS AND RESULTS: Using the National Health Insurance Service-National Health Examinee database, we identified cancer survivors diagnosed and surviving beyond 5 years post-diagnosis. SES was assessed based on insurance premiums and classified into 5 groups. The primary outcome was overall CVD mortality. This study analyzed 170 555 individuals (mean age 60.7 ± 11.9 years, 57.8% female). A gradual increase in risk was observed across SES groups: adjusted hazard ratios (95% confidence intervals) for overall CVD mortality were 1.15 (1.04-1.26), 1.28 (1.15-1.44), 1.31 (1.18-1.46), and 2.13 (1.30-3.49) for the second, third, and fourth quartile, and medical aid group (the lowest SES group) compared to the highest SES group, respectively (p for trend < 0.001). The lowest SES group with hypertension exhibited a 3.4-fold higher risk of CVD mortality compared to the highest SES group without hypertension. Interaction analyses revealed that low SES synergistically interacts with hypertension, heightening the risk of CVD mortality (synergy index 1.62). CONCLUSION: This study demonstrates a significant correlation between low SES and increased CVD mortality among cancer survivors. Particularly, the lowest SES group, when combined with hypertension, significantly escalates CVD mortality. Our findings underscore the critical importance of recognizing SES as a significant risk factor for CVD mortality in this population of cancer survivors.

Our population-based cohort study, involving over 170 000 cancer survivors, demonstrates a significant association between socioeconomic status (SES) and cardiovascular disease (CVD) mortality.

Association between low-density lipoprotein cholesterol and cardiovascular mortality in statin non-users: a prospective cohort study in 14.9 million Korean adults.

BACKGROUND: Limited information is available on detailed sex/age-specific associations between low-density lipoprotein cholesterol (LDL-C) and cardiovascular disease (CVD) mortality and 'the optimal range' associated with the lowest CVD mortality in the general population. METHODS: Korean adults (N = 14 884 975) who received routine health screenings during 2009-2010 were followed until 2018 for CVD mortality. RESULTS: During 8.8 years (mean) of follow-up, 94 344 individuals died from CVD. LDL-C had U-curve associations with mortality from CVD and its subtypes, except haemorrhagic stroke. Optimal range was 90-149 mg/dL for CVD; 70-114 for ischaemic heart disease; 85-129 for ischaemic stroke; ≥85 for subarachnoid haemorrhage; ≥130 for intracerebral haemorrhage; 115-159 for hypertension and heart failure; and 100-144 for sudden cardiac death. Assuming linear associations between 100 and 300 mg/dL, LDL-C was positively associated with CVD mortality [hazard ratio (HR) per 39-mg/dL (1-mmol/L) higher LDL-C = 1.10], largely due to ischaemic heart disease (HR = 1.26), followed by sudden cardiac death (HR = 1.13), ischaemic stroke (HR = 1.11) and heart failure (HR = 1.05). Intracerebral haemorrhage (HR = 0.90), but not subarachnoid haemorrhage, had inverse associations. Women and older adults had weaker positive associations than men and younger adults (Pinteraction < 0.001 for both sex and age). Individuals aged 75-84 years had modest positive associations with CVD mortality, especially ischaemic heart disease and ischaemic stroke. CONCLUSION: LDL-C had U-curve associations for CVD mortality. The associations and optimal ranges differed across CVD subtypes. Women and older adults had weaker positive associations than men and younger adults. Positive associations with ischaemic heart disease and ischaemic stroke were maintained in adults aged 75-84 years.

Comparison of Risk Factors for Cholangiocarcinoma and Hepatocellular Carcinoma: A Prospective Cohort Study in Korean Adults.

Cholangiocarcinoma (CCA), especially intrahepatic CCA, is known to share several risk factors with hepatocellular carcinoma (HCC) and liver cirrhosis has been proposed as a common pathogenic factor. We aimed to identify the risk factors of CCA and to examine differences in risk factors between CCA and HCC. We followed 510,217 Korean adults who underwent health checkups during 2002−2003 until 2013 via linkage to national hospital discharge records. Hazard ratios (HRs) were calculated after adjustment for confounders. During the mean follow-up of 10.5 years, 1388 and 2920 individuals were diagnosed with CCA and HCC, respectively. Choledocholithiasis (HR = 13.7; 95% confidence interval (CI) = 7.58−24.88) was the strongest risk factor for CCA, followed by cholelithiasis (HR = 2.94) and hepatitis B virus (HBV) infection (HR = 2.71). Two of the strongest risk factors for HCC­liver cirrhosis (HR = 1.29; 95% CI = 0.48−3.45) and hepatitis C virus infection (HR = 1.89; 95% CI = 0.49−7.63)­were not significantly associated with the risk of CCA. HBV infection and diabetes increased the risk of both HCC and CCA, but the HRs were lower for CCA than for HCC (Pheterogeneity < 0.001 for HBV; Pheterogeneity = 0.001 for diabetes). The magnitudes of the effects of age, sex, obesity, alcohol consumption, and smoking on the development of both cancers were different (Pheterogeneity < 0.05 for each variable). In conclusion, choledocholithiasis, cholelithiasis, HBV, older age, male sex, diabetes, smoking, alcohol drinking, and obesity were found to be potential risk factors of CCA. Liver cirrhosis did not increase the risk of CCA. The magnitudes of the potential effects of common risk factors were generally different between CCA and HCC.

High-density lipoprotein cholesterol and cardiovascular mortality: a prospective cohort study among 15.8 million adults.

AIMS: We aimed to investigate whether the associations between high-density lipoprotein cholesterol (HDL-C) and cardiovascular disease (CVD) mortality and the optimal range differ by age and CVD subtypes. METHODS AND RESULTS: Korean adults (n = 15 859 501) with no CVD/cancer who received routine health examinations during 2009-2010 were followed until 2018 for CVD mortality. During a mean 8.8 years of follow-up, 108 123 individuals died from CVD. U-curve associations were found between HDL-C and CVD mortality, regardless of sex, age, and CVD subtype. The optimal range was 50-79 mg/dL (1.29-2.06 mmol/L), while it was 40-69 (1.03-1.80), 50-79 (1.29-2.06), and 60-89 (1.55-2.32) mg/dL (mmol/L) in adults aged <45 years, 45-64 years, and 65-99 years, respectively. Assuming linear associations <60 mg/dL, the multivariable-adjusted hazard ratios (HRs) per 39 mg/dL (1 mmol/L) higher level were 0.58 (95% confidence interval = 0.56-0.60), and they were 0.61 (0.52-0.72), 0.58 (0.54-0.62), and 0.59 (0.56-0.61) in individuals aged 18-44, 45-64, and 65-99 years, respectively [Pinteraction (age) = 0.845]. Assuming linear associations in the 60-150 mg/dL range, HDL-C was positively associated with CVD mortality (HR = 1.09, 1.04-1.14). The strongest association was for sudden cardiac death (SCD) (HR = 1.37), followed by heart failure (HF) (HR = 1.20) and intracerebral haemorrhage (ICH) (HR = 1.13). The HRs were 1.47 (1.23-1.76), 1.17 (1.08-1.28), and 1.03 (0.97-1.08) in individuals aged 18-44, 45-64, and 65-99 years, respectively [Pinteraction (age) < 0.001]. CONCLUSION: Both low and high levels of HDL-C were associated with increased mortality from CVD in the general population, especially SCD, HF, and ICH. High HDL-C levels are not necessarily a sign of good cardiovascular health, especially in younger adults.

Association of Physical Activity and Lower Respiratory Tract Infection Outcomes in Patients With Cardiovascular Disease.

Background To investigate the dose-response association between physical activity and lower respiratory tract infection (LoRI) outcomes in patients with cardiovascular disease. Methods and Results Using the Korean National Health Insurance data, we identified individuals aged 18 to 99 years (mean age, 62.6±11.3 years; women, 49.6%) with cardiovascular disease who participated in health screening from January 1, 2009, to December 31, 2012 (n=1 048 502), and were followed up until 2018 for mortality and until 2019 for hospitalization. Amount of physical activity was assessed using self-reported questionnaires and categorized into 5 groups: 0 (completely sedentary), <500, 500 to 999, 1000 to 1499, and ≥1500 metabolic equivalents of task min/wk. After controlling for various confounders, adjusted hazard ratios (95% CIs) were 1.00 (reference), 0.74 (0.70-0.78), 0.66 (0.62-0.70), 0.52 (0.47-0.57), and 0.54 (0.49-0.60) for LoRI mortality, and 1.00 (reference), 0.84 (0.83-0.85), 0.77 (0.76-0.79), 0.72 (0.70-0.73), and 0.71 (0.69-0.73) for LoRI hospitalization among those engaging in physical activity of 0, <500, 500 to 999, 1000 to 1499, and ≥1500 metabolic equivalents of task min/wk, respectively. Assuming linear association between 0 and 2000 metabolic equivalents of task min/wk, each 500-metabolic equivalents of task min/wk increase of physical activity was associated with reduced LoRI mortality and hospitalization by 22% and 13%, respectively. The negative association was stronger in the older population than in the younger population (P for interaction <0.01). Conclusions In patients with cardiovascular disease, engaging in even a low level of physical activity was associated with a decreased risk of mortality and hospitalization from LoRI than being completely sedentary, and incremental risk reduction was observed with increased physical activity.

High-density lipoprotein cholesterol and all-cause mortality by sex and age: a prospective cohort study among 15.8 million adults.

BACKGROUND: The associations between high-density lipoprotein cholesterol (HDL-C) levels and all-cause mortality are unclear in young adults (<45 years) and in Asian populations. METHODS: In total, 15 860 253 Korean adults underwent routine health examinations during 2009-10 and were followed until June 2018 for all-cause mortality. Hazard ratios (HRs) were calculated using Cox proportional hazard models. RESULTS: During a mean 8.4 years of follow-up, 555 802 individuals died. U-curve associations were found between HDL-C levels and mortality, irrespective of sex or age. The HDL-C ranges associated with the lowest mortality were 40-59 and 50-69 mg/dL (1.03-1.54 and 1.29-1.80 mmol/L) in men aged <65 and ≥65 years, respectively, and the corresponding ranges were 40-69 and 50-79 mg/dL (1.03-1.80 and 1.29-2.06 mmol/L) in women aged <45 and ≥45 years, respectively. For HDL-C ranges of 60-149 mg/dL (1.55-3.86 mmol/L), each 39 mg/dL (1 mmol/L) increase in HDL-C was associated with higher mortality [men: HR = 1.39; 95% confidence interval (CI) = 1.36-1.42; women: HR = 1.15, 95% CI = 1.11-1.18], adjusting for age. These positive associations were generally stronger at younger than older ages, whereas inverse associations for HDL-C ranges <60 mg/dL (1.55 mmol/L) were strongest in middle age (45-64 years). The U-curve associations were generally unchanged after adjustment for various confounders. CONCLUSIONS: Korean adults showed U-curve associations of HDL-C with mortality, regardless of sex, and age. Younger adults had a lower optimal range and a stronger positive association with mortality than older adults in the high HDL-C range. Even moderately high HDL-C levels are not necessarily a sign of good health, especially in young adults.

Chronic Kidney Disease Increases the Risk of Hip Fracture: A Prospective Cohort Study in Korean Adults.

This study was conducted to examine the association between renal function and hip fracture. We followed up 352,624 Korean adults, who participated in health examinations during 2009-2010 until 2013. Kidney function was assessed by creatinine-based estimated glomerular filtration rate (eGFR) and albuminuria using urine reagent strip results. The incidence of hip fracture was examined by hospital discharge records. Hazard ratios (HRs) for hip fracture were calculated using Cox proportional hazard models after adjusting for multiple confounders. During a mean follow-up of 4.0 years, 1177 participants suffered a hip fracture. Lower eGFR and more severe albuminuria were associated with a higher risk of hip fracture. The HRs for hip fracture were 1.89 (95% confidence interval [CI] 1.47-2.43) and 3.75 (95% CI 2.30-6.11) among participants with eGFRs of 30 to 44 and 15 to 29 mL/min/1.73m2 relative to those with an eGFR ≥60 mL/min/1.73m2 , respectively. The HRs were 1.30 (95% CI 1.02-1.65) for moderate albuminuria and 1.58 (95% CI 1.07-2.35) for severe albuminuria (p for trend = 0.002). Participants with albuminuria had a higher risk of hip fracture than those without albuminuria, even when they belonged to the same eGFR category (HR = 1.75 versus 3.30 for an eGFR of 30 to 44 mL/min/1.73m2 ; HR = 2.72 versus 7.84 for an eGFR of 15 to 29 mL/min/1.73m2 ). The effects of each 10 mL/min/1.73m2 decrease in eGFR were stronger with advancing albuminuria severity (pinteraction = 0.016). In conclusion, both low eGFR and albuminuria were risk factors for incident hip fracture in Korean adults. Moreover, these factors exerted a synergistic effect on the risk of hip fracture. © 2020 American Society for Bone and Mineral Research.

Total cholesterol and mortality from ischemic heart disease and overall cardiovascular disease in Korean adults.

It is not completely clear whether "the lower, the better" cholesterol hypothesis for cardiovascular disease (CVD) and ischemic heart disease (IHD) can be applied to general populations with a low risk of heart disease mortality.We prospectively followed up 503,340 Koreans who participated in routine health checkups during 2002-2003 until 2013 via linkage to national mortality records.Nonlinear associations with total cholesterol (TC) were found: U-curves for overall CVD (I00-I99; nadir at 180-200 mg/dL) and a reverse-L-curve for IHD (I20-I25). Assuming a linear association in the lower range (<200 mg/dL), TC was inversely associated with CVD mortality (HR per 39 mg/dL [1 mmol/L] increase = 0.90). In the upper range (200-349 mg/dL), TC was positively associated with CVD mortality, largely due to IHD (HR = 1.19), especially acute myocardial infarction (HR = 1.23). The associations were generally similar in men versus women and in middle-aged (40-64 years) versus elderly (≥65 years) adults.TC levels of 180-200 mg/dL were associated with the lowest CVD mortality. Below 200 mg/dL, TC had no graded positive associations with IHD mortality. It remains unclear whether the lowest cholesterol levels are associated with the least mortality from CVD and IHD in Korean adults with a low risk of heart disease.

Low-normal hemoglobin levels and anemia are associated with increased risk of end-stage renal disease in general populations: A prospective cohort study.

BACKGROUND: The impact of low-normal hemoglobin (Hb) levels and anemia on the risk of end-stage renal disease (ESRD) in general populations has rarely been examined. METHODS: 510,620 Korean adults aged 40-80 years without known chronic kidney disease (CKD) underwent health examinations during 2002-2003 and were followed-up until 2013. Incidence of ESRD was identified by hospital discharge and clinical visit records. RESULTS: During a mean follow-up of 10.5, 575 women and 1047 men were diagnosed with ESRD. Lower Hb levels were associated with an increased risk of ESRD at given severity of albuminuria and at given estimated glomerular filtration rate (eGFR). Hb 13-13.9 g/dL in men, Hb 11-11.9 g/dL in women, and trace albuminuria assessed by dipstick urinalysis were associated with more than doubled risk. The risk associated with lower Hb was stronger in older (≥60 years) than younger women. Among 349,993 participants with information on eGFR, the multivariable-adjusted HRs associated with 1 g/dL lower Hb in participants with eGFR values ≥60, 30-59, and <30 mL/min/1.73 m2 were 1.34 (95% CI, 1.17-1.54), 1.55 (1.38-1.74), and 1.75 (1.47-2.09), respectively (Pinteraction between eGFR groups = .06). CONCLUSIONS: Low-normal Hb levels and anemia are risk factors for ESRD incidence in person without CKD and for CKD progression to ESRD. Lower Hb increases the risk of ESRD through synergistic biological interactions with lower eGFR and albuminuria. The impacts of lower Hb may be stronger in older than younger women. Proper management and screening at earlier stage of Hb decline and anemia might reduce the burden of CKD.

Total cholesterol and all-cause mortality by sex and age: a prospective cohort study among 12.8 million adults.

It is unclear whether associations between total cholesterol (TC) levels and all-cause mortality and the optimal TC ranges for lowest mortality vary by sex and age. 12,815,006 Korean adults underwent routine health examinations during 2001-2004, and were followed until 2013. During follow-up, 694,423 individuals died. U-curve associations were found. In the TC ranges of 50-199 and 200-449 mg/dL, each 39 mg/dL (1 mmol/L) increase in TC was associated with 23% lower (95% CI:23%,24%) and 7% higher (6%,7%) mortality, respectively. In the age groups of 18-34, 35-44, 45-54, 55-64, 65-74, and 75-99 years, each 1 mmol/L higher TC increased mortality by 14%, 13%, 8%, 7%, 6%, and 3%, respectively (P < 0.001 for each age group), for TC ≥ 200 mg/dL, while the corresponding TC changes decreased mortality by 13%, 27%, 34%, 31%, 20%, and 13%, respectively, in the range < 200 mg/dL (P < 0.001 for each age group). TC had U-curve associations with mortality in each age-sex group. TC levels associated with lowest mortality were 210-249 mg/dL, except for men aged 18-34 years (180-219 mg/dL) and women aged 18-34 years (160-199 mg/dL) and 35-44 years (180-219 mg/dL). The inverse associations for TC < 200 mg/dL were stronger than the positive associations in the upper range.