Association of Cardiovascular Mortality with Concurrent Coronary Artery Calcification and Physical Activity: A Cohort Study.

Background: Increased coronary artery calcification (CAC) has been reported in individuals with high levels of physical activity (PA). However, the association between increased CAC in a physically active population and cardiovascular mortality has not yet been well-established. This study aimed to investigate the association between PA levels and the presence or absence of CAC and cardiovascular mortality. Methods: A cohort study was conducted from 1 January 2011 to 30 December 2019. Mortality data were updated until 30 December 2020. The study population comprised 56,469 individuals who had completed the International Physical Activity Short Form Questionnaire and had undergone CAC score evaluation using a CT scan. We divided the participants into four groups: physically inactive individuals without CAC, physically inactive individuals with CAC, moderately active and health-enhancing physically active (HEPA) individuals without CAC, and moderately active and HEPA individuals with CAC. The primary outcome was cardiovascular mortality. The Cox proportional hazard model with confounding factor adjustment was conducted. Inverse probability of treatment weighting-based marginal-structural modelling was conducted. Results: The median follow-up duration was 6.60 years. The mean (SD) age of the study participants was 41.67 (±10.91) years, with 76.78% (n = 43,359) men. Compared with individuals without CAC, individuals with CAC demonstrated higher cardiovascular disease mortality regardless of PA level (Inactive and CAC > 0, HR 2.81, 95% CI: 1.76-19.19; moderately active and HEPA HR 3.27, 95% CI: 1.14-9.38). Conclusions: The presence of CAC might be associated with cardiovascular mortality regardless of PA level.

Association of Glycosylated Hemoglobin Level and Cancer-Related Mortality in Patients without Diabetes.

BACKGROUND: Previous studies have reported that abnormal glucose metabolism is associated with poor cancer outcomes. Glycated hemoglobin A1c (HbA1c) is an important indicator of glucose metabolism. This study aimed to investigate the relationship between nondiabetic HbA1c levels and cancer-related mortality. METHODS: This was a retrospective cohort study of Koreans who attended an annual or biennial health checkup program. The study group was categorized based on the quintile of HbA1c level (Q1, 3.0-5.1%; Q2, 5.2-5.3%; Q3, 5.4%; Q4, 5.5-5.6%, Q5, 5.7-6.4%). Cancer-related mortality was determined using the mortality data from the Korea National Statistical Office. Participants with an established diagnosis of diabetes or cancer were excluded. Cancer-related mortality was assessed depending on each HbA1c level with adjustment for factors that could influence mortality. RESULTS: A total of 589,457 participants were included in this study. During a median follow-up duration of 6.99 years, 1712 cancer-related deaths were reported. The risk of cancer-related mortality was significantly higher in the Q5 group (hazard ratio (HR) 1.23, range 1.02-1.47 in model 1; HR 1.25, range 1.04-1.50 in model 2). HbA1c levels were linearly associated with cancer-related deaths (Ptrend = 0.021 in model 1; 0.013 in model 2). HbA1c level and colorectal, stomach, and lung cancer mortality exhibited a positive relationship, whereas liver cancer-related mortality showed an inverse relationship with HbA1c level (Ptrend = 0.001). CONCLUSIONS: Our study showed that abnormal glucose metabolism is significantly associated with cancer-related mortality, and its relationship varies with each type of cancer.

Relationship of epicardial fat thickness and nonalcoholic fatty liver disease to coronary artery calcification: From the CAESAR study.

BACKGROUND: Epicardial fat and nonalcoholic fatty liver disease (NAFLD) are associated with subclinical atherosclerosis; however, the combined effect of both EAT and NAFLD on coronary artery calcium (CAC) is unclear. OBJECTIVE: The present study was performed to evaluate the association of both epicardial fat thickness (EFT) and NAFLD with CAC. METHODS: Among 2277 individuals enrolled in the CArdiometabolic risk, Epicardial fat, and Subclinical Atherosclerosis Registry (CAESAR) Study, 1473 individuals (1242 men, mean age, 44 ± 9 years) were included for analysis. Echocardiographic EFT and ultrasonographic fatty liver were measured. Individuals were divided into 4 groups according to EFT and NAFLD (group I: low EFT and without NAFLD; group II: low EFT and with NAFLD; group III: high EFT and without NAFLD; and group IV: high EFT and with NAFLD). RESULTS: The median EFT value (interquartiles) was 3.17 mm (2.58 mm, 3.85 mm), and the prevalence of NAFLD and CACS >0 was 46.0% and 16.8%, respectively. The prevalence of CACS >0 was 7.9%, 16.8%, 18.0%, and 26.0% in group I, II, III, and IV, respectively (P < .001). On multivariate regression after adjusting for variables with a univariate relationship (P < .20), group IV had a significantly higher OR for CACS >0, and the OR in group III was marginally significant, compared to group I (1.458 [0.795, 2.672], 1.744 [0.999, 3.046], and 1.864 [1.041, 3.337] for groups II, III, and IV, respectively). CONCLUSION: This study shows that both increased EFT and presence of NAFLD are associated with coronary artery calcification, and that increased EFT is more strongly related to CAC than NAFLD, in spite of NAFLD having greater cardiometabolic risk than EFT.

Fatty Liver, Insulin Resistance, and Obesity: Relationships With Increase in Coronary Artery Calcium Over Time.

BACKGROUND: Nonalcoholic fatty liver disease, insulin resistance (IR), and obesity frequently coexist with type 2 diabetes mellitus (DM), but it is uncertain whether these risk factors for vascular disease contribute to a change in atherosclerosis over time, independently of DM status. HYPOTHESIS: We hypothesized that the combination of fatty liver, IR, and obesity would be associated with an increase in coronary artery calcium (CAC) score over time, independently of DM status, other cardiovascular risk factors, and medications. METHODS: Data were analyzed from a South Korean occupational cohort of 2175 people. The outcome was increase in cardiac computed tomography CAC score between baseline and follow-up. Insulin resistance was defined by homeostatic model assessment of insulin resistance (HOMA-IR) ≥75th percentile and fatty liver by ultrasound. RESULTS: In 592 (27.2%) participants, CAC score increased from baseline (mean ± SD; mean age at baseline, 44.8 ± 5.5 years); and in 1583 subjects, CAC did not change or improved during follow-up (mean age, 41.6 ± 5.6 years). Diabetes mellitus, HOMA-IR, fatty liver, and obesity prevalence were all higher (all P < 0.001) in participants whose CAC score increased from baseline. Adjusting for DM and potential confounders, the combination of IR, obesity, and fatty liver was independently associated with increase in CAC score over time (hazard ratio: 2.46, 95% confidence interval: 1.50-4.03). CONCLUSIONS: The combination of fatty liver, IR, and obesity is associated with progression of atherosclerosis over time independently of DM, cardiovascular risk factors, and all medications for cardiovascular disease and DM.

Association between brachial-ankle pulse wave velocity and progression of coronary artery calcium: a prospective cohort study.

BACKGROUND: Few studies have investigated the association between coronary artery calcium (CAC) progression and arterial stiffness measured by brachial-ankle pulse wave velocity (baPWV). We examined the influence of the severity of baseline baPWV on CAC progression in a large prospective cohort. METHODS: A total of 1600 subjects who voluntarily participated in a comprehensive health-screening program between March 2010 and December 2013 and had baseline baPWV as well as CAC on baseline and serial follow-up computed tomography performed approximately 2.7 ± 0.5 years apart were enrolled in the study. RESULTS: A total of 1124 subjects were included in the analysis (1067 men; mean age, 43.6 ± 5.1 years). An increased CAC score was found in 318 subjects (28.3%) during the follow-up period. Baseline higher baPWV was significantly correlated with CAC progression, especially in subjects with third- and fourth-quartile values (adjusted odds ratio [OR] 2.04; 95% confidence interval [CI] 1.33-3.15 and OR 2.14; 95% CI 1.34-3.41, respectively) compared with the lowest-quartile values (P for trend <0.001). A similar effect was observed in diabetic subjects. Among the 835 subjects with a baseline CAC score = 0, progression to CAC score >0 was associated with male sex, diabetes, and higher baPWV. However, among the 289 individuals with a baseline CAC score >0, only the presence of CAC itself was predictive of CAC progression. CONCLUSIONS: Higher arterial stiffness measured by baPWV could be significantly associated with CAC progression.

γ-Glutamyl Transferase Is Associated with Mortality Outcomes Independently of Fatty Liver.

BACKGROUND: High serum enzyme activity levels of γ-glutamyl transferase (GGT) are associated with increased risk of mortality, but whether this is mediated by fatty liver, as a common cause of high GGT levels, is uncertain. Our aim was to test whether GGT levels are associated with all-cause, cancer, and cardiovascular (CVD) mortality, independently of fatty liver. METHODS: In an occupational cohort (n = 278 419), causes of death (International Statistical Classification of Diseases and Related Health Problems, 10th revision) were recorded over 7 years. Liver function tests and liver fat [measured by ultrasonographic standard criteria or fatty liver index (FLI)] were assessed at baseline. We used Cox proportional hazards models to estimate adjusted hazard ratios (HRs) and 95% CIs of all-cause, cancer, and CVD mortality for GGT quartiles (with lowest GGT quartile as reference). RESULTS: There were 136, 167, 265, and 342 deaths across increasing GGT quartiles. After adjusting for liver fat (by ultrasound diagnosis) in the fully adjusted model, all-cause and cancer mortality were increased in the highest GGT quartile [HR 1.50 (95% CI 1.15-1.96) and 1.57 (1.05-2.35), respectively]. For CVD mortality, the hazard was attenuated: HR 1.35 (95% CI 0.72-2.56). After adjusting for FLI in the fully adjusted model, HRs for all-cause, cancer, and CVD mortality were 1.46 (0.72-2.56), 2.03 (1.02-4.03), and 1.16 (0.41,3.24), respectively. CONCLUSIONS: There were similar hazards for all-cause and cancer mortality and attenuated hazards for CVD mortality for people in the highest GGT quartile, adjusting for fatty liver assessed by either ultrasound or FLI.

All-Cause and Cardiovascular Mortality Among Koreans: Effects of Obesity and Metabolic Health.

INTRODUCTION: The effect of obesity on mortality in people with metabolic syndrome (MetS) risk factors, but without pre-existing diabetes; hypertension; or cardiovascular disease (CVD), is uncertain. The purpose of this study is to investigate the effect of obesity and MetS risk factors on CVD and all-cause mortality in an Asian cohort. METHODS: This retrospective study included 275,867 Koreans (56.6% men) who participated in an occupational health program between 2002 and 2009. At baseline, four groups were defined, according to the absence/presence of obesity (defined by BMI < or ≥25, respectively) and zero or one or more MetS features, respectively: metabolically healthy non-obese (MHNO; reference group); metabolically healthy obese (MHO); metabolically unhealthy obese (MUO); and metabolically unhealthy non-obese (MUNO). Hazard ratios (HRs) and 95% CIs for CVD and all-cause mortality at follow-up were estimated using Cox proportional hazards models. RESULTS: During follow-up, 1,060 deaths (187 from CVD) occurred. After adjusting for age, sex, alcohol intake, exercise, and educational status, CVD mortality risk was not increased in the MHO group (HR=0.50, 95% CI=0.15, 1.66), whereas risk was increased in the MUO and MUNO groups (HR=1.81, 95% CI=1.12, 2.91; HR=1.84, 95% CI=1.15, 2.92, respectively). HRs for all-cause mortality in both obese groups were not different from the reference group. When subjects with prior diabetes, CVD, and hypertension were excluded, CVD mortality was not significantly different in the MUO and MUNO groups from the reference group. CONCLUSIONS: Comorbid diabetes, hypertension, or CVD explain much of the increased risk of CVD mortality in obese individuals.

Change in fatty liver status and 5-year risk of incident metabolic syndrome: a retrospective cohort study.

INTRODUCTION: Fatty liver is associated with metabolic syndrome (MetS) but it may also occur without MetS. Whether resolution of fatty liver in the general population affects risk of MetS is unknown. Our aim was to determine whether a change in fatty liver status (either the development of new fatty liver or the resolution of existing fatty liver) would modify the risk of de novo MetS. METHODS: Two thousand eighty-nine people without hypertension, diabetes, and MetS were examined at baseline and at 5-year follow-up using a retrospective cohort study design. Fatty liver status was assessed at baseline and at follow-up by ultrasonography. Adjusted hazard ratios (aHR) and 95 % confidence intervals (CIs) for de novo MetS at follow-up were calculated controlling for the potential confounders, compared to the reference group (people who never had fatty liver at baseline and follow-up). RESULTS: During follow-up, fatty liver developed in 251 people and fatty liver resolved in 112 people. After the adjustment for multiple confounders, persisting fatty liver and incident fatty liver development were associated with de novo MetS, with aHR of 2.60 (95 % CIs [1.61,4.20]) and 3.31 (95 % CIs [1.99,5.51]), respectively. Risk of new MetS in resolved fatty liver group was attenuated with insignificant aHR of 1.29 accompanying 95 % CIs of 0.60 and 2.80. DISCUSSION: Development or maintenance of fatty liver is positively associated with occurrence of new MetS. Resolution of fatty liver status has similar risk of de novo MetS with those who never had fatty liver. Therefore, cautious management is needed with those with fatty liver.

Relation of absolute or relative adiposity to insulin resistance, retinol binding protein-4, leptin, and adiponectin in type 2 diabetes.

BACKGROUND: Central fat mass (CFM) correlates with insulin resistance and increases the risk of type 2 diabetes and cardiovascular complications; however, peripheral fat mass (PFM) is associated with insulin sensitivity. The aim of this study was to investigate the relation of absolute and relative regional adiposity to insulin resistance index and adipokines in type 2 diabetes. METHODS: Total of 83 overweighted-Korean women with type 2 diabetes were enrolled, and rate constants for plasma glucose disappearance (K(ITT)) and serum adipokines, such as retinol binding protein-4 (RBP4), leptin, and adiponectin, were measured. Using dual X-ray absorptiometry, trunk fat mass (in kilograms) was defined as CFM, sum of fat mass on the lower extremities (in kilograms) as PFM, and sum of CFM and PFM as total fat mass (TFM). PFM/TFM ratio, CFM/TFM ratio, and PFM/CFM ratio were defined as relative adiposity. RESULTS: Median age was 55.9 years, mean body mass index 27.2 kg/m(2), and mean HbA1c level 7.12±0.84%. K(ITT) was positively associated with PMF/TFM ratio, PMF/CFM ratio, and negatively with CFM/TFM ratio, but was not associated with TFM, PFM, or CFM. RBP4 levels also had a significant relationship with PMF/TFM ratio and PMF/CFM ratio. Adiponectin, leptin, and apolipoprotein A levels were related to absolute adiposity, while only adiponectin to relative adiposity. In correlation analysis, K(ITT) in type 2 diabetes was positively related with HbA1c, fasting glucose, RBP4, and free fatty acid. CONCLUSION: These results suggest that increased relative amount of peripheral fat mass may aggravate insulin resistance in type 2 diabetes.

Inflammatory myoglandular polyps causing hematochezia.

We report herein three cases of inflammatory myoglandular polyp (IMGP) presenting as hematochezia. The polyps had pedunculated, red, and smooth features, and were 12, 12, and 15 mm in diameter and located in the sigmoid colon, transverse colon, and rectum, respectively. Endoscopic polypectomies were performed. Histologic examination of the recovered specimens revealed inflammatory granulation in the lamina propria mucosa, proliferation of smooth muscle, and hyperplastic glands with cystic dilatation. The three colon polyps were finally diagnosed both clinically and histologically as IMGP. Endoscopists should bear in mind that a polyp featuring endoscopic findings of pedunculation or semipedunculation; a red, smooth, spherical, and hyperemic surface; and patchy mucosa exudation and erosion is likely to be an IMGP.