Jeong, Seogsong

Importance Elevated low-density lipoprotein cholesterol (LDL-C) is a modifiable risk factor for cardiovascular disease, the leading cause of premature death worldwide. Assessing the LDL-C–related burden is critical for guiding prevention and treatment strategies. Objectives To estimate the global, regional, and national burden of ischemic heart disease and ischemic stroke attributable to elevated LDL-C (relative to 35-54 mg/dL) from 1990 to 2023 and to quantify the contributions of population growth, aging, risk-deleted burden, and exposure changes to burden trends. Design, Setting, and Population This comparative risk assessment, part of the Global Burden of Disease Study 2023, estimated population-level LDL-C exposure and associated health loss in 204 countries and territories. Mean LDL-C levels were estimated using spatiotemporal gaussian process regression based on 806 studies across 161 countries. Relative risks were derived from meta-analyses of 38 randomized clinical trials. Population-attributable fractions for deaths and disability-adjusted life-years (DALYs) were estimated by age and sex for adults aged 25 years or older from 1990 to 2023, with 95% uncertainty intervals. Exposure Population-level LDL-C concentrations. Main Outcomes and Measures Population-attributable fractions, counts, and rates (all ages and age standardized per 100 000) of LDL-C–attributable deaths and DALYs from ischemic heart disease and ischemic stroke, with uncertainty intervals. Results In 2023, elevated LDL-C accounted for 3.6 million deaths (95% uncertainty interval, 2.2-5.4 million; 6.0% of global mortality) and 90.7 million DALYs (95% uncertainty interval, 58.9-123.3 million; 3.2% of DALYs). Although global all-ages rates remained stable, age-standardized death and DALY rates decreased by 45.6% and 39.5%, respectively, since 1990. In 2023, age-standardized LDL-C–attributable DALY rates were highest in Eastern Europe and lowest in high-income Asia-Pacific. One-third of the global LDL-C burden occurred in India and China. Population growth and aging drove the increasing burden, with notable regional disparities in LDL-C exposure and risk-deleted DALY rates shifting toward middle-sociodemographic settings. Conclusions and Relevance Despite declining age-standardized rates, the absolute LDL-C burden has increased since 1990 due to demographic changes and has shifted toward middle-sociodemographic countries. Measurement and surveillance gaps persist. Strengthened prevention, diagnosis, and treatment access strategies are essential to mitigate the health burden of LDL-C.

Background Antibiotic use may alter gut microbiota, which could be associated with various diseases, including cardiovascular disease (CVD). Accordingly, further epidemiological evidence is needed to clarify the potential risk of CVD associated with antibiotic exposure. We evaluated the association between long‐term antibiotic exposure and CVD risk in South Korea. Methods and Results This nationwide retrospective cohort study used data from the Korean National Health Insurance Service database. A total of 2 159 965 individuals aged 40 to 79 years who had no history of antibiotic prescriptions from 2004 to 2005 were included and followed through December 31, 2021. Antibiotic exposure was defined as the cumulative days of antibiotic prescriptions from 2006 to 2010. The primary end point was incident CVD with 2 or more days of hospitalization from 2011 to 2021. Adjusted hazard ratios (aHR) and 95% CIs for CVD according to antibiotic exposure were estimated using multivariable Cox proportional hazards models, adjusting for a range of covariates. Longer cumulative antibiotic prescription days were associated with an increased risk of CVD. The aHRs for CVD associated with 1 to 14, 15 to 90, 91 to 180, 181 to 364, and ≥365 days of antibiotic exposure were 0.98 (95% CI, 0.96–1.01), 1.01 (95% CI, 0.99–1.03), 1.05 (95% CI, 1.03–1.08), 1.06 (95% CI, 1.04–1.09), and 1.10 (95% CI, 1.07–1.13) compared with those with no antibiotic prescriptions. Conclusions In this large population‐based cohort study of Korean adults, long‐term antibiotic exposure may be associated with a higher risk of CVD. Further research is warranted to establish causality and elucidate the underlying mechanisms for this association.

Nonalcoholic fatty liver disease (NAFLD) is considered an independent risk factor for the development of cardiovascular disease. However, the association between changes in NAFLD status and the risk of cardiovascular disease (CVD) remains uncertain. Starting January 1, 2013, participants were followed until the occurrence of CVD event, death, or December 31, 2020. This was a population-based cohort study that included data from adults aged ≥ 20, who underwent 2 consecutive health screenings from 2009 to 2012. NAFLD was defined as a Fatty Liver Index ≥ 60 at each screening. The primary endpoint was a CVD event, which encompassed ischemic heart disease and cerebrovascular disease. The association between changes in NAFLD status and the risk of CVD was determined using multivariable Cox proportional hazards regression. This cohort comprised 4656,305 adults with a median age of 53 years. During 36,396,968 person-years of follow-up, 238,933 (5.1%) CVD events were observed. Compared to patients with no NAFLD at both screenings, patients who developed NAFLD at the second screening exhibited an increased risk of CVD (adjusted hazard ratio, 1.15; 95% confidence interval, 1.13–1.17). In contrast, individuals who recovered from NAFLD at the second screening demonstrated a reduced CVD risk compared to those with persistent NAFLD (adjusted hazard ratio, 0.91; 95% confidence interval, 0.90–0.92). The reversal of NAFLD is associated with a reduced risk of CVD. Therefore, focusing on NAFLD treatment could serve as a clinical target for lowering CVD risk.

(1) Background: The association between proton pump inhibitor (PPI) use and hepatocellular carcinoma (HCC) has been controversial, especially in the general population. We aimed to determine the impact of PPI on HCC risk in participants without liver cirrhosis or chronic hepatitis virus infection. (2) Methods: We assessed 406,057 participants from the Korean National Health Insurance Service database who underwent health screening from 2003 to 2006. We evaluated exposure to PPI before the index date using a standardized daily defined dose (DDD) system. The association of proton pump inhibitor use with the risk of HCC was evaluated using multivariable-adjusted Cox proportional hazards regression. (3) Results: Compared with non-users, PPI use was not associated with the HCC risk in low (<30 DDDs; aHR, 1.07; 95% CI, 0.91–1.27), intermediate (30 ≤ PPI < 60 DDDs; aHR, 0.96; 95% CI, 0.73–1.26), and high (≥60 DDDs; aHR, 0.86; 95% CI, 0.63–1.17) PPI groups in the final adjustment model. In addition, risks of cirrhosis-associated HCC and non-cirrhosis-associated HCC were not significantly associated with PPI use. The results remained consistent after excluding events that occurred within 1, 2, and 3 years to exclude pre-existing conditions that may be associated with the development of HCC. We also found no PPI-associated increase in HCC risk among the selected population, such as those with obesity, older age, and chronic liver diseases. (4) Conclusions: PPI use may not be associated with HCC risk regardless of the amount. We call for future studies conducted in other regions to generalize our findings.

Abstract Background : Studies have proposed an inverse association between allergic diseases and cancer risk, but few studies to date have specifically investigated the risk of primary liver cancer (hepatocellular carcinoma, HCC; intrahepatic cholangiocarcinoma, ICC) in patients with or without allergic diseases. Objective : The aim of this study was to evaluate the association between allergic diseases and risk of developing liver cancer.Methods: A retrospective cohort study of the Korean National Health Insurance Service database was performed to study 405,512 South Korean adults ages 40 and above who underwent routine health screening after January 1st, 2005. All participants were followed for liver cancer diagnosis or death until December 31st, 2013. Those who died before the index date, had pre-diagnosed cancer, or did not undergo health screening were excluded. Cox proportional hazards regression was performed to determine the adjusted hazard ratios(aHRs) and 95% confidence intervals (CIs) for risk of developing liver cancer according presence or absence of atopic dermatitis, asthma and allergic rhinitis.Results: The aHR (95% CI) for overall liver cancer among allergic patients was 0.72 (0.64-0.81). Allergic patients had significantly reduced risk of HCC (aHR: 0.70, 95% CI: 0.61-0.81) but not ICC (aHR: 0.99, 95% CI: 0.71-1.08). Presence of allergic diseases was associated with significantly lower risk of liver cancer in both patients with (aHR: 0.61, 95% CI: 0.47-0.8) or without (aHR: 0.74, 95% CI: 0.65-0.85) chronic Hepatitis B/C infections. Presence of allergic diseases was associated with significantly lower risk of liver cancer in patients without cirrhosis (aHR: 0.72, 95% CI 0.63-0.82), but not in those with cirrhosis (aHR: 0.98, 95% CI 0.68-1.41). Patients with multiple allergies had even lower risk of liver cancer compared to patients with single allergy. Conclusion: Patients with allergic diseases have significantly lower risk of developing liver cancer compared to those without allergic diseases, which supports the rationale for immunotherapy as an effective treatment of liver cancer.