ObjectiveRecent evidence suggests that alcoholic fatty liver disease (AFLD) and non-alcoholic fatty liver disease (NAFLD) may differentially affect risk of cardiovascular mortality. To investigate ...whether early liver disease due to AFLD or NAFLD have similar or dissimilar effects on risk of early coronary artery atherosclerosis, we have investigated the associations between AFLD and NAFLD and coronary artery calcium (CAC).DesignA cross-sectional study was performed in 105 328 Korean adults who attended a health check-up programme. CAC score was assessed using CT, daily alcohol intake was recorded as grams/day and liver fat by ultrasound. Logistic regression model was used to calculate ORs with 95% CIs for prevalent CAC.ResultsBoth NAFLD and AFLD were positively associated with CAC score. After adjusting for potential confounders, multivariable-adjusted OR (95% CIs) for CAC >0 comparing NAFLD and AFLD to the reference (absence of both excessive alcohol use and fatty liver disease) were 1.10 (95% CI 1.05 to 1.16) and 1.20 (95% CI 1.11 to 1.30), respectively. In post hoc analysis, OR (95% CI) for detectable CAC comparing AFLD to NAFLD was 1.09 (95% CI 1.01 to 1.17). Associations of NAFLD and AFLD with CAC scores were similar in both non-obese and obese individuals without significant interaction by obesity (p for interaction=0.088). After adjusting for homeostasis model assessment of insulin resistance and high-sensitivity C reactive protein, the associations between fatty liver disease and CAC scores remained statistically significant.ConclusionIn this large sample of young and middle-aged individuals, early liver disease due to NAFLD and AFLD were both significantly associated with the presence of coronary artery calcification.
Background and Aims
The effects of low‐level alcohol consumption on fatty liver disease and the potential for effect modification by obesity is uncertain. We investigated associations among low‐level ...alcohol consumption, obesity status, and the development of incident hepatic steatosis (HS), either with or without an increase in noninvasive liver fibrosis score category (from low to intermediate or high category).
Approach and Results
A total of 190,048 adults without HS and a low probability of fibrosis with alcohol consumption less than 30 g/day (men) and less than 20 g/day (women) were followed for up to 15.7 years. Alcohol categories of no, light, and moderate consumption were defined as 0, 1‐9.9, and 10‐29.9 g/day (10‐19.9 g/day for women), respectively. HS was diagnosed by ultrasonography, and the probability of fibrosis was estimated using the fibrosis‐4 index (FIB‐4). Parametric proportional hazards models were used to estimate multivariable‐adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). A total of 43,466 participants developed HS, 2,983 of whom developed HS with an increase in FIB‐4 index (to intermediate or high scores). Comparing light drinkers and moderate drinkers with nondrinkers, multivariable‐adjusted HRs (95% CI) for incident HS were 0.93 (0.90‐0.95) and 0.90 (0.87‐0.92), respectively. In contrast, comparing light drinkers and moderate drinkers with nondrinkers, multivariable‐adjusted HRs (95% CI) for developing HS plus intermediate/high FIB‐4 were 1.15 (1.04‐1.27) and 1.49 (1.33‐1.66), respectively. The association between alcohol consumption categories and incident HS plus intermediate/high FIB‐4 was observed in both nonobese and obese individuals, although the association was stronger in nonobese individuals (P for interaction by obesity = 0.017).
Conclusions
Light/moderate alcohol consumption has differential effects on the development of different stages of fatty liver disease, which is modified by the presence of obesity.
In patients with acute myocardial infarction receiving potent antiplatelet therapy, the bleeding risk remains high during the maintenance phase. We sought data on a uniform unguided de-escalation ...strategy of dual antiplatelet therapy (DAPT) from ticagrelor to clopidogrel after acute myocardial infarction.
In this open-label, assessor-masked, multicentre, non-inferiority, randomised trial (TALOS-AMI), patients at 32 institutes in South Korea with acute myocardial infarction receiving aspirin and ticagrelor without major ischaemic or bleeding events during the first month after index percutaneous coronary intervention (PCI) were randomly assigned in a 1:1 ratio to a de-escalation (clopidogrel plus aspirin) or active control (ticagrelor plus aspirin) group. Unguided de-escalation without a loading dose of clopidogrel was adopted when switching from ticagrelor to clopidogrel. The primary endpoint was a composite of cardiovascular death, myocardial infarction, stroke, or bleeding type 2, 3, or 5 according to Bleeding Academic Research Consortium (BARC) criteria from 1 to 12 months. A non-inferiority test was done to assess the safety and efficacy of de-escalation DAPT compared with standard treatment. The hazard ratio (HR) for de-escalation versus active control group in a stratified Cox proportional hazards model was assessed for non-inferiority by means of an HR margin of 1·34, which equates to an absolute difference of 3·0% in the intention-to-treat population and, if significant, a superiority test was done subsequently. To ensure statistical robustness, additional analyses were also done in the per-protocol population. This trial is registered at ClinicalTrials.gov, NCT02018055.
From Feb 26, 2014, to Dec 31, 2018, from 2901 patients screened, 2697 patients were randomly assigned: 1349 patients to de-escalation and 1348 to active control groups. At 12 months, the primary endpoints occurred in 59 (4·6%) in the de-escalation group and 104 (8·2%) patients in the active control group (pnon-inferiority<0·001; HR 0·55 95% CI 0·40–0·76, psuperiority=0·0001). There was no significant difference in composite of cardiovascular death, myocardial infarction, or stroke between de-escalation (2·1%) and the active control group (3·1%; HR 0·69; 95% CI 0·42–1·14, p=0·15). Composite of BARC 2, 3, or 5 bleeding occurred less frequently in the de-escalation group (3·0% vs 5·6%, HR 0·52; 95% CI 0·35–0·77, p=0·0012).
In stabilised patients with acute myocardial infarction after index PCI, a uniform unguided de-escalation strategy significantly reduced the risk of net clinical events up to 12 months, mainly by reducing the bleeding events.
ChongKunDang Pharm, Medtronic, Abbott, and Boston Scientific.
Only a few studies have evaluated the relationship between physical activity (PA) and Homeostatic model assessment for insulin resistance (HOMA-IR). Therefore, we aimed to analyze the association ...between HOMA-IR and PA. We included 280,194 Korean without diabetes who underwent health examinations. The short form of the International Physical Activity Questionnaire was completed. PA level was divided into sedentary, mild PA, and health-enhancing PA (HEPA). The HOMA-IR levels were calculated. Confounding factors including waist circumference were adjusted. The median follow-up duration was 4.13 years. A significant inverse relationship was observed between PA level and HOMA-IR (p < 0.001). Compared with the sedentary group, HOMA-IR was lower in the HEPA group (p < 0.001), even when HEPA group decreased PA level over time (p < 0.001). Mild PA (p < 0.001) or HEPA showed a lower risk of HOMA-IR progression (p < 0.001). Increasing PA or maintaining HEPA was significantly associated with a lower HOMA-IR (p < 0.001), HOMA-IR improvement (p < 0.001), and a lower risk of HOMA-IR progression (p < 0.001). Our findings support the inverse relationship between PA and HOMA-IR in a population without diabetes. PA might improve IR and prevent its progression among populations without diabetes, independent of the waist circumference.
Context:
Fatty liver is associated with an increased risk of type 2 diabetes, but whether an increased risk remains in people in whom fatty liver resolves over time is not known.
Objective:
The ...objective of the study was to assess the risk of incident diabetes at a 5-year follow-up in people in whom: 1) new fatty liver developed; 2) existing fatty liver resolved, and 3) fatty liver severity worsened over 5 years.
Design and Methods:
A total of 13 218 people without diabetes at baseline from a Korean occupational cohort were examined at baseline and after 5 years, using a retrospective study design. Fatty liver status was assessed at baseline and follow-up as absent, mild, or moderate/severe using standard ultrasound criteria. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for incident diabetes at follow-up were estimated after controlling for multiple potential confounders.
Results:
Two hundred thirty-four people developed incident diabetes. Over 5 years, fatty liver resolved in 828, developed in 1640, and progressed from mild to moderate/severe in 324 people. Resolution of fatty liver was not associated with a risk of incident diabetes aOR 0.95 (95% CIs 0.46, 1.96), P = .89. Development of new fatty liver was associated with incident diabetes aOR 2.49 (95% CI 1.49, 4.14), P < .001. In individuals in whom severity of fatty liver worsened over 5 years (from mild to moderate/severe), there was a marked increase in the risk of incident diabetes aOR 6.13 (2.56, 95% CI 14.68) P < .001 (compared with the risk in people with resolution of fatty liver).
Conclusion:
Change in fatty liver status over time is associated with markedly variable risks of incident diabetes.
Background: Increased serum uric acid is associated with prevalence and incidence of atrial fibrillation (AF), but there is a lack of studies on the association between serum uric acid and risk of AF ...in the general population. Methods and Results: We used the data from the Kangbuk Samsung Hospital health screening cohort recorded between 2002 and 2015. The primary outcome was incidence of AF diagnosed on 12-lead electrocardiography. We analyzed and compared the hazard ratios (HR) according to baseline serum uric acid quartiles. The present study involved 282,473 subjects without baseline AF. Mean follow-up was 5.4±3.6 years. During follow-up, AF was identified in 365 subjects (cumulative incidence, 0.13%). After multivariable adjustment, including that for C-reactive protein, the risk of AF was significantly higher in the upper 2 quartiles than in the lowest quartile in men (upper third quartile: adjusted HR, 1.53; 95% confidence interval CI: 1.11–2.89; highest quartile: HR, 1.60; 95% CI: 1.13–2.25). In women, even though AF incidence rate was very low (0.6 of 10,000 person-years), the risk of AF in the highest quartile was 6.93-fold that in the lowest quartile (95% CI: 1.53–31.29). Conclusions: Serum uric acid is significantly and positively associated with incident AF in the Korean general population.
Fatty liver, diagnosed by ultrasound, significantly predicts the 5-year incidence of type 2 diabetes regardless of insulin resistance status in 11,091 healthy Koreans.
Context:
Although fatty liver ...and insulin resistance are known to be associated, the relationship between the two in the development of type 2 diabetes mellitus (T2DM) is unclear.
Objective:
We investigated the 5-yr risk of developing T2DM in individuals diagnosed with fatty liver using ultrasound and stratified by insulin sensitivity using quartiles of fasting insulin concentration.
Design and Methods:
We examined the clinical and laboratory data of 11,091 Koreans who had a medical evaluation including fasting insulin concentration and abdominal ultrasound at baseline and had a follow-up after 5 yr.
Results:
At baseline, 27% of the population had fatty liver. Almost half (47%) of the individuals with fatty liver had baseline insulin concentration in the highest quartile compared with 17% in those without fatty liver (P < 0.001). Regardless of baseline insulin concentration, individuals with fatty liver had significantly (P < 0.001) more baseline clinical and metabolic abnormalities, including higher glucose and triglyceride concentration and lower high-density lipoprotein cholesterol concentration. In addition, regardless of baseline insulin concentration, individuals with fatty liver had a significantly increased risk for incident T2DM compared with those without fatty liver crude odds ratio, 5.05 (95% confidence interval, 2.08–12.29) in the lowest insulin quartile and 6.34 (3.58–11.21) in the highest quartile. In individuals in the highest insulin quartile, the odds ratio for developing T2DM remained significant even after multivariate adjustment including baseline glucose concentration 2.42 (1.23–4.75).
Conclusion:
Although associated with insulin resistance, fatty liver diagnosed by ultrasound appears to independently increase the risk of T2DM.
OBJECTIVE: There is dissociation between insulin resistance, overweight/obesity, and fatty liver as risk factors for type 2 diabetes, suggesting that different mechanisms are involved. Our aim was to ...1) quantify risk of incident diabetes at follow-up with different combinations of these risk factors at baseline and 2) determine whether each is an independent risk factor for diabetes. RESEARCH DESIGN AND METHODS: We examined 12,853 subjects without diabetes from a South Korean occupational cohort, and insulin resistance (IR) (homeostasis model assessment-IR ≥75th centile, ≥2.0), fatty liver (defined by standard ultrasound criteria), and overweight/obesity (BMI ≥25 kg/m2) identified at baseline. Odds ratios (ORs) and 95% confidence intervals (CIs) for incident diabetes at 5-year follow-up were estimated using logistic regression. RESULTS: We identified 223 incident cases of diabetes from which 26 subjects had none of the three risk factors, 37 had one, 56 had two, and 104 had three. In the fully adjusted model, the OR and CI for diabetes were 3.92 (2.86–5.37) for IR, 1.62 (1.17–2.24) for overweight/obesity, and 2.42 (1.74–3.36) for fatty liver. The OR for the presence of all three factors in a fully adjusted model was 14.13 (8.99–22.21). CONCLUSIONS: The clustering of IR, overweight/obesity, and fatty liver is common and markedly increases the odds of developing type 2 diabetes, but these factors also have effects independently of each other and of confounding factors. The data suggest that treatment for each factor is needed to decrease risk of type 2 diabetes.
This multicenter, phase 4, Prospective Randomized Open, Blinded End‐point (PROBE) study aimed to evaluate safety and efficacy of telmisartan/rosuvastatin single‐pill combination (SPC) therapy on ...lowering central blood pressure (BP) compared with telmisartan monotherapy in hypertensive patients with dyslipidemia in Korea. Study was terminated earlier than planned due to COVID‐19 pandemic, thus should be considered as a pilot study. Among 125 patients who met the inclusion criteria of hypertension and dyslipidemia (defined as 10‐year Atherosclerotic Cardiovascular Disease risk score over 5%), 80 patients went through 4‐week single‐group run‐in period with telmisartan 40–80 mg, then randomized to telmisartan 80 mg + rosuvastatin (10 or 20 mg) SPC group or telmisartan 80 mg monotherapy group. The central/brachial BP, brachial‐ankle pulse wave velocity (baPWV), and augmentation index (AIx) were assessed at baseline and 16 weeks later. Mean brachial SBP changed from 135.80 ± 14.22 mmHg to 130.69 ± 13.23 mmHg in telmisartan/rosuvastatin group and from 134.37 ± 12.50 mmHg to 133.75 ± 12.30 mmHg in telmisartan monotherapy group without significant difference (between‐group difference p = .149). Mean central SBP were reduced significantly in the telmisartan/rosuvastatin group with change from 126.72 ± 14.44 mmHg to 121.56 ± 14.56 mmHg while telmisartan monotherapy group showed no significant change (between‐group difference p = .028). BaPWV changed from 1672.57 ± 371.72 m/s to 1591.75 ± 272.16 m/s in telmisartan/rosuvastatin group and from 1542.85 ± 263.70 m/s to 1586.12 ± 297.45 m/s in telmisartan group with no significance (between‐group difference p = .078). Change of AIx had no significant difference (between‐group difference p = .314). Both groups showed excellent compliance rate of 96.9 ± 4.5% with no significant difference in adverse rate. Telmisartan/rosuvastatin SPC therapy was more effective in lowering central BP compared with the telmisartan monotherapy. The results of this study showed benefit of additive statin therapy in hypertensive patients combined with dyslipidemia.
Adipose tissue has emerged as an attractive cell source in tissue engineering and regenerative medicine because it can be easily collected and enriched with stem/progenitor cell populations. The ...stromal vascular fraction (SVF) derived from adipose tissue contains heterogeneous cell populations such as mesenchymal progenitor/stem cells, preadipocytes, endothelial cells, pericytes, T cells, and M2 macrophages. SVF-derived mesenchymal progenitor/stem cells can be easily expanded in vitro and have the potential to create diverse lineages of cells. Although there have been issues related to their isolation and purification, SVF cells demonstrate regenerative potential in damaged tissues or organs through paracrine and differentiation mechanisms. Furthermore, SVF cells augment immunological tolerance by promoting inhibitory macrophages and T regulatory cells and by decreasing ongoing inflammation. Numerous implantations of freshly isolated, autologous adipose tissue-derived SVF cells in cosmetic surgeries and in a wide variety of other specialties support the safety of SVF cells and have accelerated their clinical application. Despite these attractive advantages of SVF cells in clinical interventions, to our knowledge the recent status of clinical studies of various diseases has not been fully investigated. Therefore this article describes recent advances in the clinical use of SVF cells, as well as the associated challenges and future directions for this field of research. We also speculate that verification of the efficacy and safety of SVF cells requires more basic experimental research, using a standard isolation protocol, and larger randomized clinical trials of the utility of SVF cells in various diseases.
PDF
