Cardiovascular Benefit of Statin Use Against Air Pollutant Exposure in Older Adults.

BACKGROUND AND AIMS: Little is known about the cardiovascular benefit of statin use against ambient air pollution among older adults who are at higher risk of cardiovascular disease (CVD) potentially owing to age-related declines in cardiovascular functions along with other risk factors. METHODS AND RESULTS: This retrospective, population-based cohort study consisted of adults aged 60 years and older free of CVD at baseline identified from the National Health Insurance Service (NHIS) database linked to the National Ambient Air Monitoring Information System (NAMIS) for average daily exposure to PM10 and PM2.5 in 2015 in the major metropolitan areas in the Republic of Korea. Follow-up period began on January 1, 2016 and lasted until December 31, 2021. Cox proportional hazards model was used to evaluate association of cardiovascular benefit with statin use against different levels of air pollutant exposure. Of 1,229,444 participants aged 60 years and older (mean age, 67.4; 37.7% male), 377,076 (30.7%) were identified as statin-users. During 11,963,322 person-years (PY) of follow-up, a total of 86,018 incident stroke events occurred (719.0 events per 100,000 PYs). Compared to statin non-user exposed to high level of PM10 (>50 µg/m3) and PM2.5 (>25 µg/m3), statin users had 20% (adjusted hazard ratio [HR], 0.80; 95% confidence intervals [CI], 0.75 to 0.85) and 17% (adjusted HR, 0.80; 95% CI, 0.80 to 0.86) lower adjusted risk of incident stroke for PM10 and PM2.5, respectively. Similar risk reduction for incident CVD was also found among statin-users exposed to low or moderate level of PM10 (≤50 µg/m3) and PM2.5 (≤25 µg/m3) exposure. CONCLUSION: Among adults aged 60 years and older with high and low or moderate levels of exposure to PM10 and PM2.5, statin use was associated with a significantly lower risk of stroke.

In a retrospective cohort study of older adults exposed to high and low or moderate levels of PM10 and PM2.5, statin use was associated with a significantly lower risk of incident stroke.

Association of blood viscosity and device-free days among hospitalized patients with COVID-19.

BACKGROUND: Increased estimated whole blood viscosity (eWBV) predicts higher mortality in patients hospitalized for coronavirus disease 2019 (COVID-19). This study assesses whether eWBV is an early predictor of non-fatal outcomes among patients hospitalized for acute COVID-19 infection. METHODS: This retrospective cohort study included 9278 hospitalized COVID-19 patients diagnosed within 48 h of admission between February 27, 2020 to November 20, 2021 within the Mount Sinai Health System in New York City. Patients with missing values for major covariates, discharge information, and those who failed to meet the criteria for the non-Newtonian blood model were excluded. 5621 participants were included in the main analysis. Additional analyses were performed separately for 4352 participants who had measurements of white blood cell count, C-reactive protein and D-dimer. Participants were divided into quartiles based on estimated high-shear blood viscosity (eHSBV) and estimated low-shear blood viscosity (eLSBV). Blood viscosity was calculated using the Walburn-Schneck model. The primary outcome was evaluated as an ordinal scale indicating the number of days free of respiratory organ support through day 21, and those who died in-hospital were assigned a value of -1. Multivariate cumulative logistic regression was conducted to evaluate the association between quartiles of eWBV and events. RESULTS: Among 5621 participants, 3459 (61.5%) were male with mean age of 63.2 (SD 17.1) years. The linear modeling yielded an adjusted odds ratio (aOR) of 0.68 (95% CI 0.59-0.79, p value < 0.001) per 1 centipoise increase in eHSBV. CONCLUSIONS: Among hospitalized patients with COVID-19, elevated eHSBV and eLSBV at presentation were associated with an increased need for respiratory organ support at 21 days. These findings are highly relevant, as they demonstrate the utility of eWBV in identifying hospitalized patients with acute COVID-19 infection at increased risk for non-fatal outcomes in early stages of the disease.

Familial Hypercholesterolemia: Challenges for a High-Risk Population: JACC Focus Seminar 1/3.

The availability of statins, ezetimibe, and PCSK9 inhibitors has significantly improved the prognosis of familial hypercholesterolemia (FH). However, a great number of individuals with FH do not achieve guideline-recommended low-density lipoprotein (LDL) cholesterol levels despite maximal lipid-lowering therapy. Novel therapies that lower LDL independent of LDL receptor activity can help mitigate atherosclerotic cardiovascular disease risk in most homozygous FH and many heterozygous FH patients. However, access to novel therapies remains limited for heterozygous FH patients with persistent elevation of LDL cholesterol despite treatment with multiple classes of cholesterol-lowering therapies. Conduction of cardiovascular outcomes clinical trials in patients with FH can be challenging because of difficulty in recruitment and long periods of follow-up. In the future, the use of validated surrogate measures of atherosclerosis may allow for clinical trials with fewer study participants and shorter duration, thereby expediting access to novel treatments for patients with FH.

Association of Blood Viscosity With Mortality Among Patients Hospitalized With COVID-19.

BACKGROUND: Coronavirus disease-2019 (COVID-19) is characterized by a dysfunctional immune response and abnormal blood rheology that contribute to endothelial dysfunction and thrombotic complications. Whole blood viscosity (WBV) is a clinically validated measure of blood rheology and an established predictor of cardiovascular risk. We hypothesize that increased WBV is associated with mortality among patients hospitalized with COVID-19. OBJECTIVES: This study sought to determine the association between estimated BV (eBV) and mortality among hospitalized COVID-19 patients. METHODS: The study population included 5,621 hospitalized COVID-19 patients at the Mount Sinai Health System from February 27, 2020, to November 27, 2021. eBV was calculated using the Walburn-Schneck model. Multivariate Cox proportional hazards models were used to evaluate the association between eBV and mortality. Considered covariates included age, sex, race, cardiovascular and metabolic comorbidities, in-house pharmacotherapy, and baseline inflammatory biomarkers. RESULTS: Estimated high-shear BV (eHSBV) and estimated low-shear BV were associated with increased in-hospital mortality. One-centipoise increases in eHSBV and estimated low-shear BV were associated with a 36.0% and 7.0% increase in death, respectively (P < 0.001). Compared with participants in the lowest quartile of eHSBV, those in the highest quartile of eHSBV had higher mortality (adjusted HR: 1.53; 95% CI: 1.27-1.84). The association was consistent among multiple subgroups, notably among patients without any comorbidities (adjusted HR: 1.69; 95% CI: 1.28-2.22). CONCLUSIONS: Among hospitalized COVID-19 patients, increased eBV is significantly associated with higher mortality. This suggests that eBV can prognosticate patient outcomes in earlier stages of COVID-19, and that future therapeutics aimed at reducing WBV should be evaluated.

Association of short-term particulate matter exposure with suicide death among major depressive disorder patients: a time-stratified case-crossover analysis.

There is growing evidence that suggests a potential association between particulate matter (PM) and suicide. However, it is unclear that PM exposure and suicide death among major depressive disorder (MDD) patients, a high-risk group for suicide. We aimed to assess the effect of short-term exposure to PM on the risk of suicide in MDD patients who are at high risk for suicide. We investigated the risk of suicide among 922,062 newly-diagnosed MDD patients from 2004 to 2017 within the Korean National Health Insurance Service (NHIS) database. We identified 3,051 suicide cases from January 1, 2015, to December 31, 2017, within the death statistics database of the Korean National Statistical Office. PMs with aerodynamic diameter less than 2.5 µm (PM2.5), less than 10 µm (PM10), and 2.5-10 µm (PM2.5-10) were considered, which were provided from the National Ambient Air Monitoring System in South Korea. Time-stratified case-crossover analysis was performed to investigate the association of particulate matter exposure to suicide events. The risk of suicide was significantly high upon the high level of exposure to PM2.5, PM2.5-10 (coarse particle) and PM10 on lag 1 (p for trend < 0.05). Short-term exposure to a high level of PM was associated with an elevated risk for suicide among MDD patients. There is a clear dose-response relationship between short-term PM exposures with suicide death among MDD patients. This result will be used as an essential basis for consideration when establishing an air pollution alarm system for reducing adverse health outcomes by PM.

Combined Associations of Physical Activity and Particulate Matter With Subsequent Cardiovascular Disease Risk Among 5-Year Cancer Survivors.

Background The combined associations of physical activity and particulate matter (PM) with subsequent cardiovascular disease (CVD) risk is yet unclear. Methods and Results The study population consisted of 18 846 cancer survivors who survived for at least 5 years after initial cancer diagnosis from the Korean National Health Insurance Service database. Average PM levels for 4 years were determined in administrative district areas, and moderate-to-vigorous physical activity (MVPA) information was acquired from health examination questionnaires. A multivariable Cox proportional hazards model was used to evaluate the risk for CVD. Among patients with low PM with particles ≤2.5 µm (PM2.5; (19.8-25.6 µg/m3) exposure, ≥5 times per week of MVPA was associated with lower CVD risk (adjusted hazard ratio [aHR], 0.77; 95% CI, 0.60-0.99) compared with 0 times per week of MVPA. Also, a higher level of MVPA frequency was associated with lower CVD risk (P for trend=0.028) among cancer survivors who were exposed to low PM2.5 levels. In contrast, ≥5 times per week of MVPA among patients with high PM2.5 (25.8-33.8 µg/m3) exposure was not associated with lower CVD risk (aHR, 0.98; 95% CI, 0.79-1.21). Compared with patients with low PM2.5 and MVPA ≥3 times per week, low PM2.5 and MVPA ≤2 times per week (aHR, 1.26; 95% CI, 1.03-1.55), high PM2.5 and MVPA ≥3 times per week (aHR, 1.34; 95% CI, 1.07-1.67), and high PM2.5 and MVPA ≤2 times per week (aHR, 1.38; 95% CI, 1.12-1.70) was associated with higher CVD risk. Conclusions Cancer survivors who engaged in MVPA ≥5 times per week benefited from lower CVD risk upon low PM2.5 exposure. High levels of PM2.5 exposure may attenuate the risk-reducing effects of MVPA on the risk of CVD.

Efficacy of Statin Therapy in Patients with Hospital Admission for COVID-19.

PURPOSE: COVID-19 is characterized by dysfunctional immune responses and metabolic derangements, which in some, lead to multi-organ failure and death. Statins are foundational lipid-lowering therapeutics for cardiovascular disease and also possess beneficial immune-modulating properties. Because of these immune-modulating properties, some have suggested their use in COVID-19. We sought to investigate the association between statin use and mortality in patients hospitalized with COVID-19. METHODS: Five thousand three hundred seventy-five COVID-19 patients admitted to Mount Sinai Health System hospitals in New York between February 27, 2020, and December 3, 2020, were included in this analysis. Statin use was classified as either non-user, low-to-moderate-intensity user, or high-intensity user. Multivariate Cox proportional hazards models were used to evaluate in-hospital mortality rate. Considered covariates were age, sex, race, and comorbidities. RESULTS: Compared to non-statin users, both low-to-moderate-intensity (adjusted hazard ratio; aHR 0.62, 95% confidential intervals; CI 0.51-0.76) and high-intensity statin users (aHR 0.53, 95% CI 0.43-0.65) had a reduced risk of death. Subgroup analysis of 723 coronary artery disease patients showed decreased mortality among high-intensity statin users compared to non-users (aHR 0.51, 95% CI 0.36-0.71). CONCLUSIONS: Statin use in patients hospitalized with COVID-19 was associated with a reduced in-hospital mortality. The protective effect of statin was greater in those with coronary artery disease. These data support continued use of statin therapy in hospitalized patients with COVID-19. Clinical trials are needed to prospectively determine if statin use is effective in lowering the mortality in COVID-19 and other viral infections.

Association of L-α Glycerylphosphorylcholine With Subsequent Stroke Risk After 10 Years.

Importance: L-α glycerylphosphorylcholine (α-GPC, choline alphoscerate) is used globally by individuals older than 50 years based on its potential function as a precursor of acetylcholine. However, choline has previously been linked to a higher risk of cardiovascular disease via trimethylamine-N-oxide, a metabolite of choline by microbiota. Objective: To investigate the association between α-GPC use and subsequent 10-year stroke risk. Design, Setting, and Participants: A population-based, retrospective cohort study was conducted using data from the National Health Insurance Service of South Korea. Participants included men and women aged 50 years or older without underlying stroke or Alzheimer disease (N = 12 008 977). Main Outcomes and Measures: All participants were divided into whether they were prescribed α-GPC during 2006-2008. α-GPC users were matched with nonusers for all covariates to create a matched cohort. α-GPC use was further divided into durations less than 2, 2 to 6, 6 to 12, and more than 12 months of α-GPC prescriptions. The adjusted hazard ratios (aHRs) and 95% CIs for total stroke, ischemic stroke, and hemorrhagic stroke from January 1, 2009, to January 31, 2018, were calculated by multivariate Cox proportional hazards regression. Results: A total of 12 008 977 individuals (6 401 965 [53.3%] women) aged 50 years or older were included in the study. The mean (SD) age was 61.6 (9.4) years for nonusers and 68.3 (10.0) years for users, and that of the matching cohort was 68.2 (9.9) years for both groups. Compared with α-GPC nonusers (n = 11 900 100), users (n = 108 877) had a higher risk for total stroke (aHR, 1.46; 95% CI, 1.43-1.48), ischemic stroke (aHR 1.36; 95% CI, 1.33-1.39), and hemorrhagic stroke (aHR, 1.36; 95% CI, 1.28-1.44). After matching for all covariates, α-GPC users had a higher risk for total stroke (aHR, 1.43; 95% CI, 1.41-1.46), ischemic stroke (aHR, 1.34; 95% CI, 1.31-1.37), and hemorrhagic stroke (aHR, 1.37; 95% CI, 1.29-1.46). Increasing intake of α-GPC was associated with a higher risk for total stroke in a dose-response manner. Conclusions and Relevance: In this cohort study, use of α-GPC was associated with a higher 10-year incident stroke risk in a dose-response manner after adjusting for traditional cerebrovascular risk factors. Future studies are needed to determine the possible mechanisms behind the potential cerebrovascular risk-elevating effects of α-GPC.

Association of Rosacea With Cardiovascular Disease: A Retrospective Cohort Study.

Background There is emerging evidence that rosacea, a chronic cutaneous inflammatory disease, is associated with various systemic diseases. However, its association with cardiovascular disease (CVD) remains controversial. We aimed to investigate whether patients with rosacea are at increased risk of developing CVD. Methods and Results This retrospective cohort study from the Korean National Health Insurance Service-Health Screening Cohort included patients with newly diagnosed rosacea (n=2681) and age-, sex-, and index year-matched reference populations without rosacea (n=26 810) between 2003 and 2014. The primary outcome was subsequent CVD including coronary heart disease and stroke. Multivariable Cox regression analyses were used to evaluate adjusted hazard ratios for subsequent CVD adjusted for major risk factors of CVD. Compared with the reference population (13 410 women; mean [SD] age, 57.7 [9.2] years), patients with rosacea (1341 women; mean [SD] age, 57.7 [9.2] years) displayed an increased risk for CVD (adjusted hazard ratios, 1.20; 95% CI, 1.03-1.40) and coronary heart disease (adjusted hazard ratios, 1.29; 95% CI, 1.05-1.60). The risk for stroke was not significantly elevated (adjusted hazard ratios, 1.12; 95% CI, 0.91-1.37). Conclusions This study suggests that patients with rosacea are more likely to develop subsequent CVD. Proper education for patients with rosacea to manage other modifiable risk factors of CVD along with rosacea is needed.

Association of Short-Term Particulate Matter Exposure among 5-Year Cancer Survivors with Incident Cardiovascular Disease: A Time-Stratified Case-Crossover Study.

The association of short-term particulate matter concentration with cardiovascular disease (CVD) among cancer survivors is yet unclear. Using the National Health Insurance Service database from South Korea, the study population consisted of 22,864 5-year cancer survivors with CVD events during the period 2015-2018. Using a time-stratified case-crossover design, each case date (date of incident CVD) was matched with three or four referent dates, resulting in a total of 101,576 case and referent dates. The daily average particulate matter 10 (PM10), 2.5 (PM2.5), and 2.5-10 (PM2.5-10) on the day of case or referent date (lag0), 1-3 days before the case or referent date (lag1, lag2, and lag3), and the mean value 0-3 days before the case or referent date (lag0-3) were determined. Conditional logistic regression was conducted to calculate the adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for CVD according to quartiles of PM10, PM2.5, and PM2.5-10. Compared to the 1st (lowest) quartile of lag0-3 PM10, the 4th (highest) quartile of lag0-3 PM10 was associated with higher odds for CVD (aOR 1.13, 95% CI 1.06-1.21). The 4th quartiles of lag1 (aOR 1.12, 95% CI 1.06-1.19), lag2 (aOR 1.09, 95% CI 1.03-1.16), lag3 (aOR 1.06, 95% CI 1.00-1.12), and lag0-3 (aOR 1.11, 95% CI 1.05-1.18) PM2.5 were associated with higher odds for CVD compared to the respective 1st quartiles. Similarly, the 4th quartile of lag0-3 PM2.5-10 was associated with higher CVD events (aOR 1.11, 95% CI 1.03-1.19) compared to the 1st quartile. Short-term exposure to high levels of PM may be associated with increased CVD risk among cancer survivors.

Associations between alcohol consumption and cardiovascular disease among long-term survivors of colorectal cancer: a population-based, retrospective cohort study.

BACKGROUND: There is no evidence whether it is best to stop drinking alcohol at all or whether it is okay to drink a little in that light-to-moderate alcohol use was associated with low cardiovascular disease (CVD) compared to non-drinker among colorectal cancer (CRC) survivors, who are regarded as vulnerable to CVD. Therefore, we evaluated the association between alcohol consumption and incident CVD among long-term survivors of CRC. METHODS: This population-based, retrospective cohort study utilized data from the Korean National Insurance Service of 20,653 long-term survivors of CRC diagnosed between 2006 and 2012. Participants were followed up to the date of CVD, death, or December 31, 2018. All patients were categorized according to their daily alcohol consumption (g/day). The outcomes were incident CVD, including ischemic heart disease (IHD) and ischemic and hemorrhagic stroke, analyzed using the Cox proportional hazards regression after adjusting for cardiovascular risk factors and history of chemotherapy and radiotherapy. RESULTS: There was no association between alcohol consumption and incident CVD among long-term survivors of CRC. Additionally, hazardous alcohol consumption (≥ 40 g/day in male patients and ≥ 20 g/day in female patients) was associated with increased CVD, ischemic stroke, and hemorrhagic stroke (adjusted hazard ratio [95% confidence interval]: 1.51 [1.15-1.97], 1.60 [1.03-2.48], and 2.65 [1.25-5.62], respectively) compared with non-drinkers. CONCLUSION: No discernable protective association was found between alcohol consumption and incident CVD for even light-to-moderate drinking among long-term survivors of CRC. Alcohol consumption ≥40 g/day in male patients and ≥ 20 g/day in female patients was associated with an increased risk of stroke compared with non-drinkers. These novel results provide useful evidence when advising survivors of CRC regarding alcohol use.

Association of first, second, and third-line bDMARDs and tsDMARD with drug survival among seropositive rheumatoid arthritis patients: Cohort study in A real world setting.

OBJECTIVES: To determine the association of first, second, and third-line biologic disease-modifying antirheumatic drugs (bDMARDs) and tofacitinib with drug survival among seropositive rheumatoid arthritis (RA) patients. METHODS: The study population was composed of 8,018 seropositive RA patients who were prescribed bDMARDs or tofacitinib between January 2014 and January 2019 from the Korean Health Insurance Review and Assessment Service database. First, second, and third-line choice of tumor necrosis factor inhibitors (TNFi) including etanercept, infliximab, adalimumab, and golimumab, as well as non-TNFi including tocilizumab, rituximab, tofacitinib, and abatacept were assessed. Multivariate Cox proportional hazards regression was used to determine the adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for drug failure according to bDMARD or tofacitinib choice starting from the initial prescription date. RESULTS: Compared to first etanercept users, patients with first tocilizumab (aHR 0.56, 95% CI 0.46-0.68), tofacitinib (aHR 0.27, 95% CI 0.18-0.42), or abatacept (aHR 0.83, 95% CI 0.69-0.99) had lower risk of drug failure. Second choice of tocilizumab (aHR 0.38, 95% CI 0.25-0.55), tofacitinib (aHR 0.23, 95% CI 0.15-0.37), or abatacept (aHR 0.54, 95% CI 0.35-0.84) was associated with lower drug failure risk compared to second etanercept users. Finally, third choice of tocilizumab (aHR 0.32, 95% CI 0.16-0.62) or tofacitinib (aHR 0.35, 95% CI 0.19-0.63) was associated with lower drug failure risk compared to third TNFi users. CONCLUSION: First and second-line tocilizumab, tofacitinib, or abatacept may lead to improved drug survival. Third-line use of tocilizumab or tofacitinib may be beneficiary in reducing drug failure risk among seropositive RA patients.

Impact of continuity of care on cardiovascular disease risk among newly-diagnosed hypertension patients.

Several previous studies have noted benefits of maintaining continuity of care (COC), including improved patient compliance, decreased health care cost, and decreased incidence of hospitalization. However, the association of COC in hypertension patients with subsequent cardiovascular disease (CVD) risk is yet unclear. Therefore, we aimed to investigate the impact of COC on CVD risk among newly-diagnosed hypertension patients. We conducted a cohort with a study population consisted of 244,187 newly-diagnosed hypertension patients in 2004 from the Korean National Health Insurance Service database. The participants were then divided into approximate quartiles of COC index, and followed from 1 January 2007 until 31 December 2017. Cox proportional hazards models were used to evaluate the adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for CVD risk according to quartiles. Compared to patients within the lowest quartile of COC index, those within the highest quartile of COC index had reduced risk for CVD (aHR 0.76, 95% confidence interval; CI 0.73-0.79), CHD (aHR 0.66, 95% CI 0.62-0.69) and stroke (aHR 0.84, 95% CI 0.80-0.88). COC among hypertension patients was associated with improved medication compliance and reduced risk of stroke and CVD. The importance of maintaining COC should be emphasized to reduce the risk of CVD among hypertension patients.

Association of combined effects of physical activity and air pollution with diabetes in older adults.

BACKGROUND: Physical activity (PA), especially outdoor PA, may have twofold effects on diabetes risk: the health benefits of PA and the potential detrimental effects caused by augmented exposure to air pollution. We examined the association of combined effects of PA and air pollution with diabetes in older adults. METHODS: The study participants consisted of 1,259,871 older adults aged 58 years or more from the Korean National Health Insurance Service database. The exposure to air pollution was estimated by the average ambient levels of particulate matter (PM) of the participants' residence area. Cox proportional hazards models were used to evaluate the adjusted hazard ratios and 95% confidence intervals of developing diabetes according to the combined effect of moderate to vigorous physical activity (MVPA) and air pollution exposure. RESULTS: Engaging in 5 or more times of MVPA/week was associated with decreased risk of diabetes within groups with both high and low/moderate levels of exposure to PM10 (low/moderate PM10 aHR 0.91, 95% CI 0.89-0.93; high PM10 aHR 0.97, 95% CI 0.94-0.99) or PM2.5 (low/moderate PM2.5 aHR 0.88, 95% CI 0.85-0.90; high PM10 aHR 0.95, 95% CI 0.91-0.99) exposure. The risk-reducing effects upon MVPA tended to be slightly attenuated, which showed the reverse J-shaped association, but still significant, among those who were exposed to a high level of air pollution. The association was consistent among stratified analyses according to the possible confounders. CONCLUSION: MVPA may be inversely associated with the risk of diabetes development within groups with both high and low/moderate levels of exposure to PM10 or PM2.5 in older adults. Future studies are necessary to validate whether the positive health effects of MVPA outweigh the potential detrimental effects due to augmented exposure to air pollution during MVPA.

The Association of 5α-Reductase Inhibitor With Suicidality.

OBJECTIVE: Using a large nationwide cohort, this study aimed to determine the risk of suicide after the use of a 5α-reductase inhibitor, an antiandrogenic medication commonly used in the treatment of lower urinary tract symptoms. METHODS: A retrospective population-based cohort study was performed using the Korean National Health Insurance Service database. The study consisted of 51,466 men 60 years or older who underwent health examinations between 2005 and 2006. Individuals using a 5α-reductase inhibitor were compared with nonusers based on drug exposure between 2003 and 2006. Individuals using a 5α-reductase inhibitor were additionally divided into tertiles based on cumulative 5α-reductase inhibitor exposure. The incidence of completed suicide was documented during 7 years of follow-up, starting January 1, 2007. RESULTS: No significant risk of suicide was observed among 5α-reductase inhibitor users compared with 5α-reductase inhibitor nonusers (hazard ratio = 1.02, 95% confidence interval = 0.70-1.48). Cumulative 5α-reductase inhibitor exposure was also not associated with increased risk of suicide (p for trend = .543). CONCLUSIONS: 5α-Reductase inhibitor use was not associated with an elevated risk of suicide during a long-term follow-up period. A limitation of this study is that possible drug exposure after the index date was not accounted for. Although 5α-reductase inhibitor may increase the risk of depressive symptoms, the present data indicate that the drug is safe in terms of long-term suicide risk.

Pre-existing Depression among Newly Diagnosed Dyslipidemia Patients and Cardiovascular Disease Risk.

BACKGROUND: Whether depression before diagnosis of dyslipidemia is associated with higher cardiovascular disease (CVD) risk among newly diagnosed dyslipidemia patients is yet unclear. METHODS: The study population consisted of 72,235 newly diagnosed dyslipidemia patients during 2003 to 2012 from the National Health Insurance Service-Health Screening Cohort of South Korea. Newly diagnosed dyslipidemia patients were then detected for pre-existing depression within 3 years before dyslipidemia diagnosis. Starting from 2 years after the diagnosis date, patients were followed up for CVD until 2015. Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for CVD were calculated by Cox proportional hazards regression. RESULTS: Compared to dyslipidemia patients without depression, those with depression had higher risk for CVD (aHR, 1.24; 95% CI, 1.09 to 1.41). Similarly, pre-existing depression was associated with increased risk for stroke (aHR, 1.27; 95% CI, 1.06 to 1.53). The risk for CVD among depressed dyslipidemia patients for high (aHR, 1.42; 95% CI, 1.06 to 1.90), medium (aHR, 1.17; 95% CI, 0.91 to 1.52), and low (aHR, 1.25; 95% CI, 1.05 to 1.50) statin compliance patients tended to be increased compared to patients without pre-existing dyslipidemia. The risk-elevating effect of depression on CVD tended to be preserved regardless of subgroups of smoking, alcohol consumption, physical activity, and body mass index. CONCLUSION: Dyslipidemia patients with pre-existing depression had increased risk for CVD. Future studies that determine CVD risk after management of depression among dyslipidemia patients are needed.

Impact of Discrepancies in General and Abdominal Obesity on Major Adverse Cardiac Events.

Background Body mass index and waist circumference (WC) are commonly used metrics that reflect general obesity and abdominal obesity. However, the impact of general and abdominal obesity discrepancies on the risk for major adverse cardiac events (MACE) is less explored. Methods and Results The study population was derived from the Korean National Health Insurance Service-Health Screening Cohort. Among 315 982 participants aged 40 years or older who underwent health examinations between 2008 and 2009, body mass index and WC were used to determine the obesity status. The participants were followed from January 1, 2010 for MACE until December 31, 2015. Cox proportional hazards models were used to evaluate the association of obesity and the risk of MACE. Compared with men who were not obese, those with abdominal obesity without general obesity (adjusted hazard ratio (aHR) 1.29, 95% CI 1.16-1.43), and general and abdominal obesity (aHR 1.20, 95% CI 1.12-1.29) had elevated risk of MACE, while those with general obesity without abdominal obesity (aHR 1.06, 95% CI 0.98-1.16) did not. Similarly, women with abdominal obesity without general obesity (aHR 1.13, 95% CI 1.03-1.24) and those with general and abdominal obesity (aHR 1.15, 95% CI 1.06-1.25) had increased risk of MACE, while those with general obesity without abdominal obesity (aHR 1.07, 95% CI 0.88-1.30) did not. Conclusions Abdominal obesity without general obesity was associated with an elevated risk of major cardiovascular outcomes while general obesity without abdominal obesity did not. Concurrent determination of body mass index and WC may be beneficial for the accurate determination of future cardiovascular risk.

Impact of weight variability on mortality among Korean men and women: a population based study.

The health consequences of weight fluctuation have been controversial and little-studied within Asian populations. We aimed to determine the effect of weight variability on mortality using Korean National Health Insurance Service - National Health Screening Cohort. Weight variability was defined as the average successive variability of body mass index (BMI) of the first (2002 and 2003), second (2004 and 2005), and third (2006 and 2007) health examinations. Then, we used Cox regression models to estimate the effect of weight variability on mortality. Compared to participants within the first quintile (lowest) of weight variability, those within the fifth quintile (highest) had increased the risk of death from all causes (hazard ratio, HR 1.33, 95% confidence interval, CI 1.26-1.41), cardiovascular disease (HR 1.31, 95% CI 1.12-1.53), cancer (HR 1.11, 95% CI 1.02-1.22), and other causes (HR 1.58, 95% CI 1.45-1.73). The risk-increasing effect of weight variability on mortality was preserved after excluding past and current smokers as well as those with pre-existing cardiovascular disease or cancer. In conclusion, high weight variability may lead to elevated risk of death even among healthy never smokers. Therefore, maintaining a steady weight should be recommended to benefit from reduced risk of death.

Association of Blood Pressure Classification in Korean Young Adults According to the 2017 American College of Cardiology/American Heart Association Guidelines With Subsequent Cardiovascular Disease Events.

Importance: Among young adults, the association of the 2017 American College of Cardiology/American Heart Association (ACC/AHA) High Blood Pressure Clinical Practice Guidelines with risk of cardiovascular disease (CVD) later in life is uncertain. Objective: To determine the association of blood pressure categories before age 40 years with risk of CVD later in life. Design, Setting, and Participants: This population-based cohort study from the Korean National Health Insurance Service consisted of 2 488 101 adults aged 20 through 39 years with blood pressure measurements taken twice from 2002 through 2005. Starting from January 1, 2006, participants were followed up until the date of CVD diagnosis, death, or December 31, 2015. Exposures: Participants were categorized by blood pressure readings: normal (systolic, <120 mm Hg; diastolic, <80 mm Hg), elevated (sytolic, 120-129 mm Hg; diastolic, <80 mm Hg), stage 1 hypertension (systolic, 130-139 mm Hg; diastolic, 80-89 mm Hg), and stage 2 hypertension (systolic, ≥140 mm Hg; diastolic, ≥90 mm Hg). Main Outcomes and Measures: The primary outcome was CVD defined as 2 or more days of hospitalization due to CVD or death due to CVD. The secondary outcomes were coronary heart disease (CHD) and stroke. Results: The study population consisted of 2 488 101 participants (median age, 31 years [interquartile range, 27-36 years], 789 870 women [31.7%]). A total of 44 813 CVD events were observed during a median follow-up duration of 10 years. Men with baseline stage 1 hypertension compared with those with normal blood pressure had higher risk of CVD (incidence, 215 vs 164 per 100 000 person-years; difference, 51 per 100 000 person-years [95% CI, 48-55]; adjusted hazard ratio [HR], 1.25 [95% CI, 1.21-1.28]), CHD (incidence, 134 vs 103 per 100 000 person-years; difference, 31 per 100 000 person-years [95% CI, 28-33]; adjusted HR, 1.23 [95% CI, 1.19-1.27]), and stroke (incidence, 90 vs 67 per 100 000 person-years; difference, 23 per 100 000 person-years [95% CI, 21-26]; adjusted HR, 1.30 [95% CI, 1.25-1.36]). Women with baseline stage 1 hypertension compared with those with normal blood pressure had increased risk of CVD (incidence, 131 vs 91 per 100 000 person-years; difference, 40 per 100 000 person-years [95% CI, 35-45]; adjusted HR, 1.27 [95% CI, 1.21-1.34]), CHD (incidence, 56 vs 42 per 100 000 person-years; difference, 14 per 100 000 person-years [95% CI, 11-18]; adjusted HR, 1.16 [95% CI, 1.08-1.25]), and stroke (incidence, 79 vs 51 per 100 000 person-years; difference, 28 per 100 000 person-years [95% CI, 24-32]; adjusted HR [1.37, 95% CI, 1.29-1.46]). Results for state 2 hypertension were consistent. Conclusions and Relevance: Among Korean young adults, stage 1 and stage 2 hypertension, compared with normal blood pressure, were associated with increased risk of subsequent cardiovascular disease events. Young adults with hypertension, defined by the 2017 ACC/AHA criteria, may be at increased risk of cardiovascular disease.