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Background: Atherosclerotic cardiovascular disease (ASCVD) risk estimation based on the pooled cohort equation (PCE) overestimates in population-based cohorts. Whether it performs equally across disaggregated demographics in health care populations is less known., Objectives: The purpose of the study was to recalibrate PCE and rederive prevention thresholds in a contemporary health care system and evaluate its performance across sociodemographics., Methods: We retrospectively inspected electronic health records between 2010 to 2012 and 2020 to 2022 within Mass General Brigham health care in New England region. We compared performance of the original vs recalibrated PCE measured by calibration, discrimination, reclassification rate, and net benefit among 160,926 patients aged 40 to 79 years and without prior ASCVD or lipid-lowering medication., Results: Of the 160,926 patients (mean age: 54.6 ± 8.6 years; 61.4% female), 20,373 (12.7%) developed ASCVD over 10 years. The original PCE globally underestimated ASCVD risk (observed vs predicted incidence rate: 0.13 vs 0.05). Recalibration upclassified risk primarily among individuals with low-to-borderline risk by the original PCE and additionally identified 40% of patients who had undergone ASCVD events yet deemed statin-ineligible based on the original PCE. Treatment thresholds yielding the greatest net benefit were ≥24.0% for women (+23.3%) vs ≥26.0% for men (+18.7%), whereas ≥26.0% for White or other race (+24.7%) vs ≥14.0% Black or African American (+12.5%), respectively. Specifically, Hispanic or Latino and non-Hispanic Black patients conferred the greatest sensitivity improvement at ≥12.3% threshold compared to higher ≥23.6% among non-Hispanic Asian or Pacific Islanders. Generally, lower thresholds earlier in life were optimal., Conclusions: Recalibration and personalized treatment thresholds derived within a health system may improve prevention treatment allocation efficiency., Competing Interests: Dr Cho is supported by a grant of the Korea Health Technology R&D Project through the 10.13039/501100003710Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health and Welfare, Republic of Korea (grant no.: HI19C1330). Dr Paruchuri is supported in part by the Massachusetts General Hospital Executive Committee on Research Fund for Medical Discovery Population Healthcare Sciences Research Fellowship Award. Dr Honigberg is supported by grants from the 10.13039/100000050National Heart, Lung, and Blood Institute (K08HL166687) and the 10.13039/100000968American Heart Association (940166, 979465). Dr Natarajan is supported by grants from the 10.13039/100000050National Heart, Lung, and Blood Institute (R01HL142711, R01HL127564, R01HL148050, R01HL151283, R01HL148565, R01HL135242, and R01HL151152), the National Human Genetics Research Institute (U01HG011719), the 10.13039/100000062National Institute of Diabetes and Digestive and Kidney Diseases (R01DK125782), 10.13039/501100001674Fondation Leducq (TNE-18CVD04), and 10.13039/100005294Massachusetts General Hospital (Paul and Phyllis Fireman Endowed Chair in Vascular Medicine). The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Dr Bhattacharya reports prior advisory relationship with Casana Care, Inc unrelated to the current work. Dr Paruchuri has received research support from Genetech, 10.13039/100004336Novartis, and Allelica, all unrelated to this work. Dr Honigberg has received consulting fees from CRISPR Therapeutics and Comanche Biopharma; advisory board service for Miga Health; and research support from Genetech, all unrelated to the present work. Dr Natarajan has received personal consulting fees from Allelica, Amgen, Apple, AstraZeneca, Blackstone Life Sciences, Foresite Labs, Genentech/Roche, Novartis, and TenSixteen Bio; investigator-initiated grants from Apple, 10.13039/100004325AstraZeneca, 10.13039/100002429Amgen, Genentech/Roche, 10.13039/100004336Novartis, and 10.13039/100008497Boston Scientific; is a co-founder of TenSixteen Bio, is a scientific advisory board member of Esperion Therapeutics, TenSixteen Bio, and geneXwell; and spousal employment at Vertex, all unrelated to the present work. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

Competing Interests: Conflict of interest: P.N. reports research grants from Allelica, Amgen, Apple, Boston Scientific, Genentech/Roche, and Novartis, personal fees from Allelica, Apple, AstraZeneca, Blackstone Life Sciences, Creative Education Concepts, CRISPR Therapeutics, Eli Lilly & Co, Foresite Labs, Genentech/Roche, GV, HeartFlow, Magnet Biomedicine, Merck, and Novartis, scientific advisory board membership of Esperion Therapeutics, Preciseli, and TenSixteen Bio, scientific co-founder of TenSixteen Bio, equity in MyOme, Preciseli, and TenSixteen Bio, and spousal employment at Vertex Pharmaceuticals, all unrelated to the present work. M.C.H. reports consulting fees from Comanche Biopharma, advisory board service for Miga Health, and grant support from Genentech. The remaining authors report no disclosures.

Coronary artery disease (CAD) is the leading cause of death among adults worldwide. Accurate risk stratification can support optimal lifetime prevention. Current methods lack the ability to incorporate new information throughout the life course or to combine innate genetic risk factors with acquired lifetime risk. We designed a general multistate model (MSGene) to estimate age-specific transitions across 10 cardiometabolic states, dependent on clinical covariates and a CAD polygenic risk score. This model is designed to handle longitudinal data over the lifetime to address this unmet need and support clinical decision-making. We analyze longitudinal data from 480,638 UK Biobank participants and compared predicted lifetime risk with the 30-year Framingham risk score. MSGene improves discrimination (C-index 0.71 vs 0.66), age of high-risk detection (C-index 0.73 vs 0.52), and overall prediction (RMSE 1.1% vs 10.9%), in held-out data. We also use MSGene to refine estimates of lifetime absolute risk reduction from statin initiation. Our findings underscore our multistate model's potential public health value for accurate lifetime CAD risk estimation using clinical factors and increasingly available genetics toward earlier more effective prevention., (© 2024. The Author(s).)

Background and Aims: Clonal haematopoiesis of indeterminate potential (CHIP), the age-related expansion of blood cells with preleukemic mutations, is associated with atherosclerotic cardiovascular disease and heart failure. This study aimed to test the association of CHIP with new-onset arrhythmias., Methods: UK Biobank participants without prevalent arrhythmias were included. Co-primary study outcomes were supraventricular arrhythmias, bradyarrhythmias, and ventricular arrhythmias. Secondary outcomes were cardiac arrest, atrial fibrillation, and any arrhythmia. Associations of any CHIP [variant allele fraction (VAF) ≥ 2%], large CHIP (VAF ≥10%), and gene-specific CHIP subtypes with incident arrhythmias were evaluated using multivariable-adjusted Cox regression. Associations of CHIP with myocardial interstitial fibrosis [T1 measured using cardiac magnetic resonance (CMR)] were also tested., Results: This study included 410 702 participants [CHIP: n = 13 892 (3.4%); large CHIP: n = 9191 (2.2%)]. Any and large CHIP were associated with multi-variable-adjusted hazard ratios of 1.11 [95% confidence interval (CI) 1.04-1.18; P = .001] and 1.13 (95% CI 1.05-1.22; P = .001) for supraventricular arrhythmias, 1.09 (95% CI 1.01-1.19; P = .031) and 1.13 (95% CI 1.03-1.25; P = .011) for bradyarrhythmias, and 1.16 (95% CI, 1.00-1.34; P = .049) and 1.22 (95% CI 1.03-1.45; P = .021) for ventricular arrhythmias, respectively. Associations were independent of coronary artery disease and heart failure. Associations were also heterogeneous across arrhythmia subtypes and strongest for cardiac arrest. Gene-specific analyses revealed an increased risk of arrhythmias across driver genes other than DNMT3A. Large CHIP was associated with 1.31-fold odds (95% CI 1.07-1.59; P = .009) of being in the top quintile of myocardial fibrosis by CMR., Conclusions: CHIP may represent a novel risk factor for incident arrhythmias, indicating a potential target for modulation towards arrhythmia prevention and treatment., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Importance: Hypertensive disorders of pregnancy (HDPs), including gestational hypertension and preeclampsia, are important contributors to maternal morbidity and mortality worldwide. In addition, women with HDPs face an elevated long-term risk of cardiovascular disease., Objective: To identify proteins in the circulation associated with HDPs., Design, Setting, and Participants: Two-sample mendelian randomization (MR) tested the associations of genetic instruments for cardiovascular disease-related proteins with gestational hypertension and preeclampsia. In downstream analyses, a systematic review of observational data was conducted to evaluate the identified proteins' dynamics across gestation in hypertensive vs normotensive pregnancies, and phenome-wide MR analyses were performed to identify potential non-HDP-related effects associated with the prioritized proteins. Genetic association data for cardiovascular disease-related proteins were obtained from the Systematic and Combined Analysis of Olink Proteins (SCALLOP) consortium. Genetic association data for the HDPs were obtained from recent European-ancestry genome-wide association study meta-analyses for gestational hypertension and preeclampsia. Study data were analyzed October 2022 to October 2023., Exposures: Genetic instruments for 90 candidate proteins implicated in cardiovascular diseases, constructed using cis-protein quantitative trait loci (cis-pQTLs)., Main Outcomes and Measures: Gestational hypertension and preeclampsia., Results: Genetic association data for cardiovascular disease-related proteins were obtained from 21 758 participants from the SCALLOP consortium. Genetic association data for the HDPs were obtained from 393 238 female individuals (8636 cases and 384 602 controls) for gestational hypertension and 606 903 female individuals (16 032 cases and 590 871 controls) for preeclampsia. Seventy-five of 90 proteins (83.3%) had at least 1 valid cis-pQTL. Of those, 10 proteins (13.3%) were significantly associated with HDPs. Four were robust to sensitivity analyses for gestational hypertension (cluster of differentiation 40, eosinophil cationic protein [ECP], galectin 3, N-terminal pro-brain natriuretic peptide [NT-proBNP]), and 2 were robust for preeclampsia (cystatin B, heat shock protein 27 [HSP27]). Consistent with the MR findings, observational data revealed that lower NT-proBNP (0.76- to 0.88-fold difference vs no HDPs) and higher HSP27 (2.40-fold difference vs no HDPs) levels during the first trimester of pregnancy were associated with increased risk of HDPs, as were higher levels of ECP (1.60-fold difference vs no HDPs). Phenome-wide MR analyses identified 37 unique non-HDP-related protein-disease associations, suggesting potential on-target effects associated with interventions lowering HDP risk through the identified proteins., Conclusions and Relevance: Study findings suggest genetic associations of 4 cardiovascular disease-related proteins with gestational hypertension and 2 associated with preeclampsia. Future studies are required to test the efficacy of targeting the corresponding pathways to reduce HDP risk.

Background: The clinical significance of isolated diastolic hypertension defined by the 2017 American College of Cardiology/American Heart Association blood pressure (BP) guidelines remains inconsistent. We examined whether long-term diastolic burden predicts the first major adverse cardiovascular event in participants with sustained and untreated normal systolic BP., Methods: The Mass General Brigham Biobank is a New England health care-based cohort recruited between 2010 and 2021. A total of 15 979 participants aged 18 to 64 years and without prior cardiovascular disease, antihypertensives, or high systolic BP were studied. The cumulative diastolic burden was determined as the area under the curve for diastolic BP (DBP) ≥80 mm Hg over 5 years before enrollment. Major adverse cardiovascular event was defined as a composite of first incident ischemic heart disease, stroke, heart failure, or all-cause death., Results: Of the 15 979 participants, mean (SD) age at enrollment was 47.6 (14.3) years, 11 950 (74.8%) were women, and the mean (SD) systolic BP and DBP were 118.0 (12.9) and 72.2 (9.3) mm Hg, respectively. Over a median (interquartile range) follow-up of 3.5 (1.8-5.4) years, 2467 (15.4%) major adverse cardiovascular events occurred. Using Cox proportional hazards regression, each SD increase in cumulative DBP was independently associated with a hazard ratio (95% CI) of 1.06 (1.02-1.10) without effect modification by sex ( P =0.65), age ( P =0.46), or race/ethnicity ( P =0.24). In addition to traditional risk factors, cumulative DBP modestly improved the discrimination C index (95% CI) from 0.74 (0.72-0.75) to 0.75 (0.74-0.76; likelihood ratio test, P =0.037)., Conclusions: Among individuals with normal systolic BP, cumulative DBP may augment cardiovascular disease risk stratification beyond a single DBP measure and traditional risk factors., Competing Interests: Disclosures M.C. Honigberg reports consulting fees from CRISPR Therapeutics, advisory board service for Miga Health, and research support from Genentech; P. Natarajan reports personal consulting fees from Allelica, Amgen, Apple, AstraZeneca, Blackstone Life Sciences, Foresite Labs, Genentech/Roche, Novartis, and TenSixteen Bio, investigator-initiated grants from Apple, AstraZeneca, Amgen, Genentech/Roche, Novartis, and Boston Scientific is a cofounder of TenSixteen Bio, is a scientific advisory board member of Esperion Therapeutics, TenSixteen Bio, and geneXwell, and spousal employment at Vertex, all unrelated to the present work. The other authors report no conflicts.

Aims: Complications of coronary artery disease (CAD) represent the leading cause of death among adults globally. This study examined the associations and clinical utilities of genetic, sociodemographic, lifestyle, and clinical risk factors on CAD recurrence., Methods and Results: Data were from 7024 UK Biobank middle-aged adults with established CAD at enrolment. Cox proportional hazards regressions modelled associations of age at enrolment, age at first CAD diagnosis, sex, cigarette smoking, physical activity, diet, sleep, Townsend Deprivation Index, body mass index, blood pressure, blood lipids, glucose, lipoprotein(a), C reactive protein, estimated glomerular filtration rate (eGFR), statin prescription, and CAD polygenic risk score (PRS) with first post-enrolment CAD recurrence. Over a median [interquartile range] follow-up of 11.6 [7.2-12.7] years, 2003 (28.5%) recurrent CAD events occurred. The hazard ratio (95% confidence interval [CI]) for CAD recurrence was the most pronounced with current smoking (1.35, 1.13-1.61) and per standard deviation increase in age at first CAD (0.74, 0.67-0.82). Additionally, age at enrolment, CAD PRS, C-reactive protein, lipoprotein(a), glucose, low-density lipoprotein cholesterol, deprivation, sleep quality, eGFR, and high-density lipoprotein (HDL) cholesterol also significantly associated with recurrence risk. Based on C indices (95% CI), the strongest predictors were CAD PRS (0.58, 0.57-0.59), HDL cholesterol (0.57, 0.57-0.58), and age at initial CAD event (0.57, 0.56-0.57). In addition to traditional risk factors, a comprehensive model improved the C index from 0.644 (0.632-0.654) to 0.676 (0.667-0.686)., Conclusion: Sociodemographic, clinical, and laboratory factors are each associated with CAD recurrence with genetic risk, age at first CAD event, and HDL cholesterol concentration explaining the most., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Importance: To address systemic disparities in biomedical research, the All of Us (AoU) Research Program was created to identify the root causes and consequences of health outcomes in the US. However, the extent of AoU's racial and ethnic diversity is unknown., Objective: To quantify representation of key racial and ethnic groups in the accruing AoU nationwide health cohort and compare with their actual representation in the US., Design, Setting, and Participants: This cohort study compared the AoU program from May 2017 to June 2022 for individuals 18 years and older with the Decennial Survey 2020 (DEC) collected by the US Census Bureau., Exposures: Representation of non-Hispanic Asian, non-Hispanic Black or African American, Hispanic or Latino, non-Hispanic White, and uncategorized or multiple races in AoU., Main Outcomes and Measures: The extent of underrepresentation or overrepresentation of each racial group in the AoU program at both nationwide and state-level relative to DEC., Results: Of the 358 705 US adults in the AoU to date, individuals identified with the following race and ethnicity categories: 12 710 non-Hispanic Asian (3.5%), 73 348 non-Hispanic Black or African American (20.5%), 58 488 Hispanic or Latino (16.3%), 205 457 non-Hispanic White (57.3%), and 8702 uncategorized or reporting multiple categories (2.4%). Of 355 413 participants with available sex at birth and age data, 218 981 (61.6%) were female and had a mean (SD) age of 53.1 (17.0) years, 136 037 (38.28%) were male and had a mean (SD) age of 56.7 (17.0) years, and 395 reported nonbinary sex (0.1%), with a mean (SD) age of 55.4 (15.8) years. Compared with the referent US, non-Hispanic Black or African American individuals were overrepresented in the AoU by 8.73% (AoU, 20.5% [73 348 of 358 705] vs DEC, 11.7% [30 266 080 of 258 343 281]) and by relative scale, 1.94-fold. Non-Hispanic White individuals accounted for the greatest participation in the AoU with generally consistent dominance across all regions yet numerically underrepresented by absolute difference of -3.54% (95% CI, -3.70 to -3.38). Uncategorized or multiracial group in the AoU (2.4% [8702 of 358 705]) was 0.43-fold likely to be represented relative to the DEC (4.6% [11 922 096 of 258 343 281]) with an absolute difference of -2.19% (95% CI, -2.24 to -2.14). Moreover, non-Hispanic Asian individuals were underrepresented by -2.54% (95% CI, -2.60 to -2.48) prominently in most states. Individuals identifying as Hispanic or Latino were nominally underrepresented by -0.46% (95% CI, -0.58 to -0.34) (AoU, 16.3% [58 488 of 358 705] vs DEC, 16.8% [43 322 792 of 258 343 281])., Conclusions and Relevance: Recruitment trends for the ongoing AoU show relatively improved representation of some major race groups with geographic trends. These findings underscore the need to further tailor and augment recruitment and participation initiatives for diverse populations.

Preeclampsia and gestational hypertension are common pregnancy complications associated with adverse maternal and child outcomes. Current tools for prediction, prevention and treatment are limited. Here we tested the association of maternal DNA sequence variants with preeclampsia in 20,064 cases and 703,117 control individuals and with gestational hypertension in 11,027 cases and 412,788 control individuals across discovery and follow-up cohorts using multi-ancestry meta-analysis. Altogether, we identified 18 independent loci associated with preeclampsia/eclampsia and/or gestational hypertension, 12 of which are new (for example, MTHFR-CLCN6, WNT3A, NPR3, PGR and RGL3), including two loci (PLCE1 and FURIN) identified in the multitrait analysis. Identified loci highlight the role of natriuretic peptide signaling, angiogenesis, renal glomerular function, trophoblast development and immune dysregulation. We derived genome-wide polygenic risk scores that predicted preeclampsia/eclampsia and gestational hypertension in external cohorts, independent of clinical risk factors, and reclassified eligibility for low-dose aspirin to prevent preeclampsia. Collectively, these findings provide mechanistic insights into the hypertensive disorders of pregnancy and have the potential to advance pregnancy risk stratification., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background: Clonal hematopoiesis of indeterminate potential (CHIP)-the age-related clonal expansion of blood stem cells with leukemia-associated mutations-is a novel cardiovascular risk factor. Whether CHIP remains prognostic in individuals with established atherosclerotic cardiovascular disease (ASCVD) is less clear., Objectives: This study tested whether CHIP predicts adverse outcomes in individuals with established ASCVD., Methods: Individuals aged 40 to 70 years from the UK Biobank with established ASCVD and available whole-exome sequences were analyzed. The primary outcome was a composite of ASCVD events and all-cause mortality. Associations of any CHIP (variant allele fraction ≥2%), large CHIP clones (variant allele fraction ≥10%), and the most commonly mutated driver genes (DNMT3A, TET2, ASXL1, JAK2, PPM1D/TP53 [DNA damage repair genes], and SF3B1/SRSF2/U2AF1 [spliceosome genes]) with incident outcomes were compared using unadjusted and multivariable-adjusted Cox regression., Results: Of 13,129 individuals (median age: 63 years) included, 665 (5.1%) had CHIP. Over a median follow-up of 10.8 years, any CHIP and large CHIP at baseline were associated with adjusted HRs of 1.23 (95% CI: 1.10-1.38; P < 0.001) and 1.34 (95% CI: 1.17-1.53; P < 0.001), respectively, for the primary outcome. TET2 and spliceosome CHIP, especially large clones, were most strongly associated with adverse outcomes (large TET2 CHIP: HR: 1.89; 95% CI: 1.40-2.55; P <0.001; large spliceosome CHIP: HR: 3.02; 95% CI: 1.95-4.70; P < 0.001)., Conclusions: CHIP is independently associated with adverse outcomes in individuals with established ASCVD, with especially high risks observed in TET2 and SF3B1/SRSF2/U2AF1 CHIP., Competing Interests: Funding Support and Author Disclosures Mr Schuermans is supported by the Belgian American Educational Foundation. Dr Cho is supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant no.: HI19C1330). Dr Yu is supported by the National Heart, Lung, and Blood Institute (5T32HL007604-37). Dr Weeks is supported by the Robert Wood Johnson Foundation/American Society of Hematology Harold Amos Medical Faculty Development Program, Edward P. Evans Foundation, and Wood Foundation. Dr Niroula is supported by funds from the Knut and Alice Wallenberg Foundation (no. KAW2017.0436). Dr Jaiswal is supported by the Burroughs Wellcome Fund Career Award for Medical Scientists, Fondation Leducq (TNE-18CVD04), the Ludwig Center for Cancer Stem Cell Research at Stanford University, and the National Institute of Health Director's New Innovator Award (DP2-HL157540); and is a founding scientific advisor to and shareholder in TenSixteen Bio. Dr Libby is a founding scientific advisor to TenSixteen Bio; has been an unpaid consultant to or involved in clinical trials for Amgen, AstraZeneca, Baim Institute, Beren Therapeutics, Esperion Therapeutics, Genentech, Kancera, Kowa Pharmaceuticals, Medimmune, Merck, Norvo Nordisk, Novartis, Pfizer, and Sanofi-Regeneron; has been a member of the scientific advisory boards for Amgen, Caristo, Cartesian, CSL Behring, DalCor Pharmaceuticals, Dewpoint, Kowa Pharmaceuticals, Olatec Therapeutics, Medimmune, Novartis, PlaqueTec, and XBiotech Inc; has received research funding in the past 2 years from Novartis; is on the Board of Directors of and has financial interest in XBiotech Inc; and is an inventor on a patent (“Use of canakinumab”) related to this work filed by Brigham and Women’s Hospital (U.S. patent application no. 20200239564, filed 18 August 2020). Dr Ebert is supported by grants from the National Institutes of Health, National Cancer Institute, and National Heart, Lung, and Blood Institute (R01-HL082945 and P01-CA066996), Fondation Leducq (TNE-18CVD04), the EvansMDS Foundation, and the Howard Hughes Medical Institute; has received research funding from Celgene, Deerfield, Novartis, and Calico; has received consulting fees from GRAIL; and has been a member of the scientific advisory board and a shareholder for Neomorph Inc, TenSixteen Bio, Skyhawk Therapeutics, and Exo Therapeutics. Dr Bick has received grants from Burroughs Wellcome Foundation Career Award for Medical Scientists and the National Institute of Health Director's Early Independence Award (DP5-OD029586); and is a founding scientific advisor to and shareholder in TenSixteen Bio. Dr Natarajan has received grants for the Hassenfeld Scholar Award from the Massachusetts General Hospital, the National Heart, Lung, and Blood Institute (R01HL1427, R01HL148565, and R01HL148050), Fondation Leducq (TNE-18CVD04), Amgen, Apple, AstraZeneca, Boston Scientific, and Novartis; has received spousal employment and equity at Vertex; has received consulting fees from Apple, AstraZeneca, Novartis, Genentech/Roche, Blackstone Life Sciences, Foresite Labs, and TenSixteen Bio; and has been a scientific advisor board member and shareholder for TenSixteen Bio and geneXwell (all unrelated to this work). Dr Honigberg is supported by the National Heart, Lung, and Blood Institute (K08HL166687) and the American Heart Association (940166, 979465); has received consulting fees from CRISPR Therapeutics; has been on the advisory board service for Miga Health; and has received grant support from Genentech (all unrelated to this work). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Importance: Hypertension remains the major cardiovascular disease risk factor globally, but variability in measured blood pressure may result in suboptimal management. Whether genetic contributors to elevated blood pressure may complementarily inform cardiovascular disease risk assessment is unknown., Objective: To examine incident cardiovascular disease by blood pressure polygenic risk score independent of measured blood pressures and antihypertensive medication prescriptions., Design, Setting, and Participants: The cohort study (UK Biobank) recruited UK residents aged 40 to 69 years between March 2006 and August 2010. Participants without a prior physician diagnosis of cardiovascular disease, including myocardial infarction, stroke, or heart failure, were included. Excluded were individuals with mismatch between self-reported and genotypically inferred sex, sex aneuploidy, missing genotype rates of 1% or greater, and excess genotypic heterozygosity. Data analyses were performed from September 25, 2021, to July 21, 2022., Exposures: Measured blood pressure and externally derived blood pressure polygenic risk score stratified by hypertension diagnosis and management, which included normal blood pressure (<130/80 mm Hg without antihypertensives), untreated hypertension (systolic blood pressure ≥130 mm Hg or diastolic blood pressure ≥80 mm Hg without antihypertensives), and treated hypertension (current antihypertensives prescriptions)., Main Outcomes and Measures: Composite of first incident myocardial infarction, stroke, heart failure, or cardiovascular-related death., Results: Of the 331 078 study participants included (mean [SD] age at enrollment, 56.9 [8.1] years; 178 824 female [54.0%]), 83 094 (25.1%) had normal blood pressure, 197 597 (59.7%) had untreated hypertension, and 50 387 (15.2%) had treated hypertension. Over a median (IQR) follow-up of 11.1 (10.4-11.8) years, the primary outcome occurred in 15 293 participants. Among those with normal blood pressure, untreated hypertension, and treated hypertension, each SD increase in measured systolic blood pressure was associated with hazard ratios of 1.08 (95% CI, 0.93-1.25), 1.20 (95% CI, 1.16-1.23), and 1.16 (95% CI, 1.11-1.20), respectively, for the primary outcome. Among these same categories, each SD increase in genetically predicted systolic blood pressure was associated with increased hazard ratios of 1.13 (95% CI, 1.05-1.20), 1.04 (95% CI, 1.01-1.07), and 1.06 (95% CI, 1.02-1.10), respectively, for the primary outcome independent of measured blood pressures and other covariates. Findings were similar for measured and genetically predicted diastolic blood pressure., Conclusions and Relevance: Blood pressure polygenic risk score may augment identification of individuals at heightened cardiovascular risk, including those with both normal blood pressure and hypertension. Whether it may also guide antihypertensive initiation or intensification requires further study.

Background Favorable cardiovascular health (CVH) in young adulthood has been associated with lower future cardiovascular risk. We determined whether CVH and its sex differences in young adults have changed from 2007 to 2018. Methods and Results We identified 10 206 individuals, aged 20 to 39 years, from the National Health Examination and Nutrition Survey data. CVH was assessed on the basis of the American Heart Association's Life's Simple 7 metrics (of 7). Changes in the mean number of ideal CVH components and the ideal proportion of individual components were calculated using linear regression analysis. Changes in sex difference trends were assessed with an interaction term between sex and calendar year. The mean (SD) age of the study population was 29.3 (5.8) years, and 5260 (51.5%) individuals were women. The mean (SD) ideal CVH component remained unchanged for both women (4.40 [1.22] to 4.48 [1.15]; P =0.94) and men (3.97 [1.27] to 3.93 [1.24]; P =0.87), with stable sex differences ( P for interaction=0.94). Nonetheless, sex differences in blood pressure widened as ideal blood pressure decreased in men (54.0% to 46.9%; P =0.03) but not in women ( P for interaction <0.001). Concurrently, the proportion with ideal physical activity declined in women (57.3% to 49.4%; P =0.04) but remained stable in men ( P for interaction=0.03). Nonsmoking increased to a greater extent in women (64.1% to 70.5%; P =0.05) than in men ( P for interaction=0.01). Conclusions Sex disparities in CVH have persisted with exacerbated differences in blood pressure, physical activity, and smoking. These insights provide opportunities to promote equitable CVH.

Objective: Increasing number of clinical guidelines are adopting comprehensive cardiovascular risk assessment tools for treatment decision and disease management. Yet, little is known regarding cardiovascular risks associated with the length of favourable cardiometabolic profile. In this context, we examined whether the duration of strictly ideal cardiovascular health (CVH), based on body mass index, blood pressure, fasting glucose, total cholesterol, cigarette smoking, alcohol drinking and physical activity, in middle age is associated with risk of developing chronic kidney disease (CKD) and cardiovascular disease (CVD) in mid-to-late life., Methods: From the Korean Genome and Epidemiology Study Ansung-Ansan cohort, we included 8020 participants (median age 50.0 years, 47.9% male), of whom, 7854 without CKD and 7796 without CVD at baseline. Cox proportional hazards models were employed to assess CKD and CVD risks, adjusting for age, sex, education level, examination sites and renal markers., Results: Over a median follow-up of 15.0 years, 1401 cases of CKD and 493 cases of CVD were newly developed. Compared with participants with <5 years of ideal CVH duration, HR (95% CI) of those who maintained for 5-<10 years or ≥10 years had negatively graded risks for CKD (5-<10 years, 0.63 (0.39 to 0.93); ≥10 years, 0.33 (0.15 to 0.74)) and CVD (5-<10 years, 0.83 (0.54 to 1.27); ≥10 years, 0.22 (0.08 to 0.60)). In parallel, participants with delayed decline to suboptimal level had lower disease risks compared with counterparts with consistently suboptimal CVH., Conclusion: Our findings confer that maintaining favourable health behaviours and clinical risk factor levels in midlife will improve later-life cardiovascular outcomes., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Objectives: We illustrated sex- and age-specific temporal trends in cardiovascular health among Korean adults., Methods: From the Korean National Health and Nutrition Examination Survey 2007-2018, we included 61,408 participants aged 20 years or older. The ideal levels of 6 components of cardiovascular health metrics were defined as never-smoking, ≥75 min/week of vigorous or ≥150 min/week of moderate-to-vigorous physical activity, body mass index (BMI) <23 kg/m², total cholesterol <200 mg/dL, blood pressure (BP) <120/80 mmHg, and fasting glucose <100 mg/dL. Temporal trends in the number of ideal cardiovascular health components and distribution of each component were assessed by sex and age., Results: The average number of ideal cardiovascular health components decreased from 3.37 in 2007-2009 to 2.86 in 2016-2018. Never smoking increased from 56.0% to 59.2%, largely contributed by young men. Ideal physical activity halved (41.4-21.3%); such decline was more pronounced in women and with older age. Ideal BMI decreased from 44.3% to 42.2%, more apparently in young and elderly men. In contrast, ideal BMI increased in middle-aged and elderly women. Ideal cholesterol decreased from 65.5% to 50.3%, profoundly in young adults and relatively greater in men. Ideal BP declined from 55.1% to 46.9%, more evidently in men. However, ideal BP discernibly increased in middle-aged women. Ideal glucose decreased from 74.6% to 66.0%, comparatively greater and earlier in men., Conclusions: The proportion of Korean adults with ideal cardiovascular health decreased between 2007 and 2018, but the course of responsible factors differed across sex and age groups., Competing Interests: The authors have no financial conflicts of interest., (Copyright © 2021. The Korean Society of Cardiology.)

Background: Benefits of intensive blood pressure lowering on health outcomes have been demonstrated in high-risk patients. However, little is known about such benefits in patients with left ventricular hypertrophy (LVH)., Objectives: This study sought to investigate the association of on-treatment blood pressure with cardiovascular disease (CVD) risk in adults with hypertension and LVH., Methods: From a nationwide health examination database, this study identified 95,545 participants aged 40-79 years who were taking antihypertensive medication and had LVH on baseline electrocardiography. Using Cox models, HRs and 95% CIs for CVD events were calculated according to systolic blood pressure (SBP) or diastolic blood pressure (DBP)., Results: Over a median follow-up of 11.5 years, 12,035 new CVD events occurred. An SBP of <130 mm Hg and DBP of <80 mm Hg were associated with the lowest risk for CVD events in cubic spline models. When the group with SBP of 120-129 mm Hg was the reference, multivariable-adjusted HRs were 1.31 (95% CI: 1.24-1.38) in the ≥140 mm Hg group, 1.08 (95% CI: 1.02-1.15) in the 130-139 mm Hg group, and 1.03 (95% CI: 0.93-1.15) in the <120 mm Hg group. Likewise, when the group with DBP of 70-79 mm Hg was the reference, multivariable-adjusted HRs were 1.30 (95% CI: 1.24-1.37) in the ≥90 mm Hg group, 1.06 (95% CI: 1.01-1.12) in the 80-89 mm Hg group, and 1.08 (95% CI: 0.96 to 1.20) in the <70 mm Hg group., Conclusions: In adults with hypertension and LVH, the risk for CVD events was the lowest at SBP <130 mm Hg and DBP <80 mm Hg. Further randomized trials are warranted to establish optimal blood pressure-lowering strategies for these patients., Competing Interests: Funding Support and Author Disclosures This work was supported by the Korea Health Technology Research and Development Project through the Korea Health Industry Development Institute funded by the Ministry of Health and Welfare, Republic of Korea (grant HI13C0715). The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Although abnormal blood pressure (BP) patterns are associated with adverse cardiorenal outcomes, their associations are yet unquantified by nocturnal dipping status. We examined the association of nocturnal BP dipping pattern with albuminuria and kidney function among participants with controlled hypertension without prior advanced kidney disease., Methods: Ambulatory BP (ABP) measurements were collected from 995 middle-aged, cardiology clinic patients with controlled office BP (OBP) (<140/90 mm Hg). The magnitude of dipping was calculated as the difference between daytime and nighttime systolic BP (SBP) divided by daytime SBP. Accordingly, the participants were categorized as extreme-dipper (≥20%), dipper (10% to <20%), non-dipper (0% to <10%), or reverse-dipper (<0%). We analyzed the cross-sectional associations of dipping with albuminuria (urine albumin-to-creatinine ratio ≥30 mg/g) and decreased estimated glomerular filtration rate (<60 ml/min/1.73 m2), adjusting for OBP/ABP, antihypertensive class, body mass index, total cholesterol, fasting glucose, socioeconomic status, and health behavior., Results: The participants (mean age 60.2 years; 52.9% male) consisted of 13.5% extreme-dippers, 43.1% dippers, 34.7% non-dippers, and 8.7% reverse-dippers. In reference to dippers, odds ratios [95% confidence interval] for albuminuria were 1.73 [1.04-2.60] in reverse-dippers, 1.67 [1.20-2.32] in non-dippers, and 0.62 [0.38-1.04] in extreme-dippers. Likewise, abnormal dipping profile was associated with decreased kidney function: reverse-dipping, 2.02 [1.06-3.84]; non-dipping, 1.98 [1.07-3.08]; extreme-dipping, 0.69 [0.20-1.17]. The associations persisted among participants with more conservatively controlled OBP (<130/80 mm Hg)., Conclusions: Monitoring diurnal and nocturnal BP may identify chronic kidney disease otherwise overlooked based on OBP., (© American Journal of Hypertension, Ltd 2021. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Purpose: Evidence suggests that physical activity participation is shaped through a myriad of structural aspects of social relationships. We examined the relationship between social network structure based on egocentric social network and physical activity., Methods: From 6799 middle-aged Korean adults, we assessed the social network density and proportion of closed triads, using the name generator module. Self-reported physical activity for functional and leisure purposes was calculated in metabolic equivalent of task (MET)-min/week. We employed sex-stratified, multivariable linear regression to assess the association between each network structure variable and total physical activity, adjusting for age, network size, socioeconomic status, and comorbidities. We also examined the association with moderate-to-vigorous physical activity (MVPA) and wrist-worn accelerometer assessed physical activity., Results: The network members of female participants were more likely to be of same sex and family member compared to those of males. There were no sex differences in average network size. Network density based on affiliation was sex-differentially associated with physical activity (male β -346.7, p 0.2221 and female β -528.6, p 0.0002). In parallel, the proportion of closed triads was negatively associated with physical activity only in females (male β -542.6, p 0.0551 and female β -641.51, p < 0.0001). However, network density and closed triads were insignificantly yet positively associated with MVPA in male (density β 229.7, p 0.3193 and closed triad β 109.21, p 0.6333). Network structure by contact frequency or emotional closeness and accelerometer-assessed physical activity showed inconsistent results., Conclusion: Understanding the role of social network structures can help to achieve ideal physical activity level in the context of primary prevention of cardiometabolic disorders., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Physical activity has been known to deter inflammatory process; yet, the evidence is scarce in healthy, middle-aged population. We assessed the association between physical activity and inflammatory biomarkers, including high sensitivity (hs) C-reactive protein, interleukin (IL)-1α, -1β, and -6, tumor necrosis factor (TNF) -α and -β, and monocyte chemotactic protein (MCP) -1 and -3. Functional and leisure-time physical activity was assessed by the International Physical Activity Questionnaire. Inflammatory biomarkers were measured by multiplex enzyme-linked immunosorbent assay. Compared with highly physically active participants based on total metabolic equivalent of task, the most sedentary group had significantly higher odds ratio and [95% confidence interval] for ≥75th percentile of TNF-α (1.64 [1.10-2.44]), TNF-β (1.50 [1.09-2.07]), IL-1β (2.14 [1.49-3.09]), hsIL-1β (1.72 [1.15-2.58]), IL-6 (1.84 [1.24-1.73]), hsIL-6 (2.05 [1.35-3.12]), and MCP-1 (1.91 [1.28-2.87]) levels. Results for IL-1α and MCP-3 were inconsistent, as the least active group had lower odds for above the median IL-1α (0.65 [0.49-0.95]) and MCP-3 (0.71 [0.54-0.93]) yet higher odds for ≥75th percentile IL-1α (2.36 [1.63-3.42]) and MCP-3 (2.44 [1.63-3.64]) levels. Based on duration of moderate-to-vigorous physical activity, sedentary participants had significantly higher odds for above median (1.40 [1.13-1.73]) and ≥75th percentile (1.33 [1.00-1.77]) IL-1β compared with those fulfilling the guideline recommendation. Subgroup analyses showed minimal sex differences. Routine inflammatory assessment may help to achieve primordial prevention of cardiovascular and metabolic diseases. Novelty: Healthy, middle-aged adults with physically active lifestyle were generally at lower odds for elevated inflammatory status. The associations persisted regardless of sex, age, comorbidities, adiposity, and diet.

Background and Objectives: Cardiovascular disease (CVD) is the leading cause of death and disability worldwide. To provide an overview of the temporal trends in the burden of CVD, the Korean Society of Cardiology has published the Korea Heart Disease Fact Sheet in 2020., Methods: We analyzed anonymized data of the Causes of Death Statistics, National Health Insurance Claims Database, and Korea National Health and Nutrition Examination Survey to assess mortality, hospitalizations, and risk factors for CVD., Results: The CVD mortality decreased until 2010, then steadily increased up to 123 per 100,000 persons in 2018. Since 2002, the number and rate of CVD hospitalization have continued to grow. In 2018, approximately 12.1 million Korean adults had hypertension, 4.3 million had diabetes, 8.7 million had hypercholesterolemia, 14.9 million had obesity, and 8.8 million were currently smoking. The number of risk factors increased markedly with older age; 58.4% of adults age ≥70 years had ≥2 risk factors., Conclusions: CVD mortality and hospitalization have gradually increased in the last decade, and a substantially high proportion of adults were carrying more than 1 cardiovascular risk factor in 2018. With the rapid population aging, a continued increase in CVD appears inevitable in Korea. Concerted and sustained approaches are essential to achieve early prevention and reduce the burden of CVD., Competing Interests: The authors declare that there is no conflict of interest relevant to this work., (Copyright © 2021. The Korean Society of Cardiology.)

Objective: The Korean Society of Lipid and Atherosclerosis (KSoLA) has published the Dyslipidemia Fact Sheets in Korea 2020 to provide an overview of magnitude and management status of dyslipidemia and their recent trends therein., Methods: The Fact Sheets were based on the analyses of Korean adults aged 20 years or older of the 2007-2018 Korea National Health and Nutrition Examination Survey (KNHANES) and the 2002-2018 National Health Insurance Big Data (NHI-BD)., Results: Between 2007 and 2018, the crude prevalence of hypercholesterolemia increased from 9.0% to 20.7%. During the same period, its management rate also improved yet remained unsatisfactory. In 2018, the prevalence of dyslipidemia was 45.6% in men and 31.3% in women, which increased with older age and presence of metabolic abnormalities. Indeed, the number of people diagnosed with dyslipidemia has increased nearly 8-fold from 1.5 million in 2002 to 11.6 million in 2018; alongside, the number of people receiving pharmacological treatment for dyslipidemia has also risen. Of the 7.7 million people treated for dyslipidemia in 2018, statin accounted for the majority (91.8%) of lipid-lowering drug prescriptions, followed by ezetimibe (14.6%), fibrate (8.5%), and omega-3 acid (5.9%). The most frequently used combination therapy was statin plus ezetimibe, accounting for 72% of dual therapy prescriptions., Conclusion: Dyslipidemia continues to impose a substantial disease burden in Korea. Both healthcare practitioners and patients need to actively adopt guideline-recommended lifestyle modification and pharmacological treatment for comprehensive, timely, and sustained management., Competing Interests: Conflict of Interest: The authors have no conflict of interest to declare., (Copyright © 2021 The Korean Society of Lipid and Atherosclerosis.)

Background and Objectives: Understanding the trends in cardiovascular disease (CVD) mortality is important for developing burden reduction strategies. Based on the Cause of Death Statistics, we examined the changing patterns of CVD mortality in Korea between 1983 and 2018., Methods: Causes of death were coded according to the International Classification of Disease, 10th revision. Deaths from all diseases of circulatory system (I00-I99) and the following 6 subcategories were analyzed: total heart diseases (I00-I13 and I20-I51), hypertensive heart diseases (I10-I13), ischemic heart diseases (I20-I25), myocardial infarction (I21-I23), heart failure (I50), and cerebrovascular diseases (I60-I69). Crude, age-standardized, and age-stratified rates were calculated to assess temporal trends in CVD mortality., Results: The number of deaths and crude mortality rate for all diseases of circulatory system increased recently mainly due to the population ageing. Specifically, total heart diseases showed increasing trend, whereas cerebrovascular diseases showed decreasing trend. Between 1983 and 2018, age-standardized mortality rates significantly declined for all diseases of circulatory system, total heart diseases, hypertensive heart diseases, and cerebrovascular diseases. Age-standardized mortality rates for ischemic heart diseases and myocardial infarction peaked in the early 2000s then decreased thereafter. However, age-standardized mortality rate for heart failure rapidly increased, especially in recent years., Conclusions: CVD mortality in Korea has remarkably decreased over the last 36 years. However, the recent rise in the absolute number of deaths from heart diseases, especially from heart failure, calls for attention in prevention and management of CVD and its sequelae., Competing Interests: The authors have no financial conflicts of interest., (Copyright © 2021. The Korean Society of Cardiology.)

[Figure: see text].

Background: The Korean Society of Hypertension has published the Korea Hypertension Fact Sheet 2020 to provide an overview of the magnitude and management status of hypertension and their recent trends., Methods: The Fact Sheets were based on the analyses of Korean adults aged 20 years or older of the 2007-2018 Korea National Health and Nutrition Examination Survey (KNHANES) and the 2002-2018 National Health Insurance Big Data (NHI-BD)., Results: Currently, the population average of systolic/diastolic blood pressure was 118/76 mmHg in Korean adults aged 20 years or older showing little change in the recent decade. However, the number of people with hypertension increased steadily, exceeding 12.0 million. Indeed, the number of people diagnosed with hypertension increased from 3.0 million in 2002 to 9.7 million in 2018. During the same period, the number of people using antihypertensive medication increased from 2.5 million to 9.0 million, and the number of people adherent to treatment increased from 0.6 million to 6.5 million. Hypertension awareness, treatment, and control rates increased rapidly until 2007, but showed plateaued thereafter. In 2018, the awareness, treatment, and control rates of hypertension among all adults were 67, 63, and 47%, respectively. However, the awareness and treatment rates were only 17 and 14% among adults aged 20 to 39 years old with hypertension. Among patients treated for hypertension, 61% of them were also using glucose-lowering or lipid-lowering drugs. Among antihypertensive prescriptions, 41% of the patients received monotherapy, 43% received dual therapy, and 16% received triple or more therapy. The most commonly prescribed antihypertensive medication was angiotensin receptor blockers, followed by calcium channel blockers and diuretics., Conclusion: To achieve further improvement in management of hypertension, we need to encourage awareness and treatment in young adults. It is required to develop tailored prevention and management strategies that are appropriate for and inclusive of various demographics.

Background: Metabolic disorders are established precursors to cardiovascular diseases, yet they can be readily prevented with sustained lifestyle modifications., Objective: We assessed the effectiveness of a smartphone-based weight management app on metabolic parameters in adults at high-risk, yet without physician diagnosis nor pharmacological treatment for metabolic syndrome, in a community setting., Methods: In this 3-arm parallel-group, single-blind, randomized controlled trial, we recruited participants aged 30 to 59 years with at least 2 conditions defined by the Third Report of the National Cholesterol Education Program expert panel (abdominal obesity, high blood pressure, high triglycerides, low high-density lipoprotein cholesterol, and high fasting glucose level). Participants were randomly assigned (1:1:1) by block randomization to either the nonuser group (control), the app-based diet and exercise self-logging group (app only), or the app-based self-logging and personalized coaching from professional dieticians and exercise coordinators group (app with personalized coaching). Assessments were performed at baseline, week 6, week 12, and week 24. The primary outcome was change in systolic blood pressure (between baseline and follow-up assessments). Secondary outcomes were changes in diastolic blood pressure, body weight, body fat mass, waist circumference, homeostatic model of assessment of insulin resistance, triglyceride level, and high-density lipoprotein cholesterol level between baseline and follow-up assessments. Analysis was performed using intention-to-treat., Results: Between October 28, 2017 and May 28, 2018, 160 participants participated in the baseline screening examination. Participants (129/160, 80.6%) who satisfied the eligibility criteria were assigned to control (n=41), app only (n=45), or app with personalized coaching (n=43) group. In each group, systolic blood pressure showed decreasing trends from baseline (control: mean -10.95, SD 2.09 mmHg; app only: mean -7.29, SD 1.83 mmHg; app with personalized coaching: mean -7.19, SD 1.66 mmHg), yet without significant difference among the groups (app only: P=.19; app with personalized coaching: P=.16). Instead, those in the app with personalized coaching group had greater body weight reductions (control: mean -0.12, SD 0.30 kg; app only: mean -0.35, SD 0.36 kg, P=.67; app with personalized coaching: mean -0.96, SD 0.37 kg; P=.08), specifically by body fat mass reduction (control: mean -0.13, SD 0.34 kg; app only: mean -0.64, SD 0.38 kg, P=.22; app with personalized coaching: mean -0.79, SD 0.38 kg; P=.08)., Conclusions: Simultaneous diet and exercise self-logging and persistent lifestyle modification coaching were ineffective in lowering systolic blood pressure but effective in losing weight and reducing body fat mass. These results warrant future implementation studies of similar models of care on a broader scale in the context of primary prevention., Trial Registration: ClinicalTrials.gov NCT03300271; http://clinicaltrials.gov/ct2/show/NCT03300271., (©So Mi Jemma Cho, Jung Hyun Lee, Jee-Seon Shim, Hyungseon Yeom, Su Jin Lee, Yong Woo Jeon, Hyeon Chang Kim. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 09.10.2020.)

Background: Inflammatory cytokines are increasingly utilized to detect high-risk individuals for cardiometabolic diseases. However, with large population and assay methodological heterogeneity, no clear reference currently exists., Methods: Among participants of the Cardiovascular and Metabolic Diseases Etiology Research Center cohort, of community-dwelling adults aged 30 to 64 without overt cardiovascular diseases, we presented distributions of tumor necrosis factor (TNF)-α and -β, interleukin (IL)-1α, -1β, and 6, monocyte chemoattractant protein (MCP)-1 and -3 and high sensitivity C-reactive protein (hsCRP) with and without non-detectable (ND) measurements using multiplex enzyme-linked immunosorbent assay. Then, we compared each markers by sex, age, and prevalence of type 2 diabetes mellitus, hypertension, and dyslipidemia, using the Wilcoxon Rank-Sum Test., Results: In general, there were inconsistencies in direction and magnitude of differences in distributions by sex, age, and prevalence of cardiometabolic disorders. Overall, the median and the 99th percentiles were higher in men than in women. Older participants had higher TNF-α, high sensitivity IL-6 (hsIL-6), MCP-1, hsCRP, TNF-β, and MCP-3 median, after excluding the NDs. Participants with type 2 diabetes mellitus had higher median for all assayed biomarkers, except for TNF-β, IL-1α, and MCP-3, in which the medians for both groups were 0.00 due to predominant NDs. Compared to normotensive group, participants with hypertension had higher TNF-α, hsIL-6, MCP-1, and hsCRP median. When stratifying by dyslipidemia prevalence, the comparison varied significantly depending on the treatment of NDs., Conclusion: Our findings provide sex-, age-, and disease-specific reference values to improve risk prediction and diagnostic performance for inflammatory diseases in both population- and clinic-based settings.

Background: Evidence suggests that habitual snoring is an independent risk factor for poor glycemic health. We examined the associations between snoring with prediabetes and diabetes in Korean population., Methods: Self-reported snoring characteristics were collected from 3,948 middle-aged adults without prior cardiovascular diseases. Multivariable linear regression assessed the association of snoring intensity, frequency, disruptiveness, and disrupted breathing with fasting glucose and glycosylated hemoglobin (HbA1c) level. Then, multinomial regression evaluated how increasing snoring symptoms are associated with the risk for prediabetes and diabetes, adjusting for socioeconomic and behavioral risk factors of diabetes, obesity, hypertension, and other sleep variables., Results: Higher snoring intensity and frequency were positively associated with fasting glucose and HbA1c levels. Participants presenting the most severe snoring were at 1.84 times higher risk (95% confidence interval [CI], 1.09 to 2.29) for prediabetes and 2.24 times higher risk (95% CI, 1.84 to 2.95) for diabetes, compared to non-snorers. Such graded association was also observed amongst the most frequent snorers with higher risk for prediabetes (odds ratio [OR], 1.78; 95% CI, 1.29 to 2.22) and diabetes (OR, 2.03; 95% CI, 1.45 to 2.85). Disruptive snoring (OR, 1.60; 95% CI, 1.12 to 2.28) and near-daily disruptive breathing (OR, 2.18; 95% CI, 1.02 to 4.19) were associated with higher odds for diabetes. Such findings remained robust after additional adjustment for sleep duration, excessive daytime sleepiness, unwakefulness, and sleep-deprived driving., Conclusion: Snoring is associated with impaired glucose metabolism even in otherwise metabolically healthy adults. Habitual snorers may require lifestyle modifications and pharmacological treatment to improve glycemic profile.

Background This study aimed to investigate the association between depression and the augmentation index (AIx), and to further investigate whether there is a difference in this association according to the patients' inflammatory status. Methods This study included 458 men and 815 women (mean age: 49.35 years), a community-dwelling and middle-aged Korean population. The Korean version of the Beck Depression Inventory-II (BDI-II) was used to assess depressive symptoms. Arterial stiffness was evaluated via an AIx normalized to 75 beats/min. We confirmed two factors from BDI-II after conducting a factor analysis. Multiple regression models were used after adjusting for socio-demographic factors, lifestyle factors, systolic blood pressure, diabetes history, and body mass index. We further stratified the data according to inflammatory biomarkers with cutoffs of the 75 th percentile. Results There was a significant positive association between the BDI-II score and arterial stiffness (ß= 0.09, p-value=0.037). In women, the somatic-affective factor showed a stronger positive association (ß= 0.20, p-value=0.018) with arterial stiffness than the cognitive factor (ß= 0.12, p-value=0.148). There was no significant association in men (ß= -0.01, p-value=0.943). In subgroup analyses, women showed significant positive associations between the somatic affective factor of depressive symptoms on and arterial stiffness according to both inflammatory markers (IL-6: ß= 0.17, p-value=0.039; hs-CRP: ß= 0.17, p-value=0.094) Limitations The design of the cross-sectional study limits causal interpretation. Conclusion Depression and its somatic-affective factor were positively associated with arterial stiffness in women. Inflammatory status may be involved in modifying the association between depressive symptoms, its sub-factors, and AIx., Competing Interests: Declaration of Competing Interest None, (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Little is known regarding health outcomes associated with isolated systolic hypertension (ISH), isolated diastolic hypertension (IDH), or systolic and diastolic hypertension (SDH) among young adults with stage 1 hypertension, defined using the 2017 American College of Cardiology/American Heart Association blood pressure (BP) guideline., Methods: From a nationwide health screening database, we included 6 424 090 participants, aged 20 to 39 years, who were not taking antihypertensive medication at the baseline examination in 2003 to 2007. Participants were categorized as having normal BP (untreated systolic BP [SBP] <120/diastolic BP [DBP] <80 mm Hg; n=2 665 310); elevated BP (SBP 120-129/DBP <80 mm Hg; n=705 344); stage 1 IDH (SBP <130/DBP 80-89 mm Hg; n=1 271 505); stage 1 ISH (SBP 130-139/DBP <80 mm Hg; n=255 588); stage 1 SDH (SBP 130-139/DBP 80-89 mm Hg; n=711 503); and stage 2 hypertension (SBP ≥140, DBP ≥90 mm Hg; n=814 840). The primary outcome was composite cardiovascular disease (CVD) events, including myocardial infarction, stroke, heart failure, and CVD-related death., Results: The median age of the participants was 30 years and 60.9% were male. Over a median follow-up of 13.2 years, 44 070 new CVD events occurred. With normal BP as the reference, multivariable-adjusted hazard ratios (95% CIs) for CVD events were 1.14 (1.09-1.18) for elevated BP, 1.32 (1.28-1.36) for stage 1 IDH, 1.36 (1.29-1.43) for stage 1 ISH, 1.67 (1.61-1.72) for stage 1 SDH, and 2.40 (2.33-2.47) for stage 2 hypertension., Conclusions: Among young adults, stage 1 ISH, IDH, and SDH were all associated with higher CVD risks than normal BP. The CVD risks of stage 1 ISH and IDH were similar to each other but lower than the risk of stage 1 SDH. Categorizing young adults with stage 1 hypertension further into stage 1 ISH, IDH, and SDH may improve risk stratification for identifying high-risk individuals.

Background and Objectives: This study compared the potential impacts of the 2017 American College of Cardiology/American Heart Association (ACC/AHA) and the 2018 Korean Society of Hypertension (KSH) guidelines on prevalence of hypertension, recommended antihypertensive treatment, and achievement of target blood pressure (BP) in Korean population., Methods: We analyzed the 2007-2017 Korea National Health and Nutrition Examination Survey data to calculate guideline-specific hypertension prevalence and treatment implications on 59,767 adults aged 20 years or older by sex and age., Results: The prevalence of hypertension was markedly higher 46.3% by the ACC/AHA guideline due to the lowered BP cutoff than 25.9% by the KSH guideline; the increase was most pronounced in young adults. Yet, there was only a marginal 1.6% increase in the percentage of adults suggested pharmacological approach by the ACC/AHA guideline, but selectively in the older subgroups. Overall, 45.6% of Korean adults treated for hypertension failed to meet BP goal according to the KSH guideline; the underachievement extended to 61.7% of participants according to the ACC/AHA guideline., Conclusions: The lowered BP threshold, 130/80 mmHg, by the 2017 ACC/AHA guideline, in conjuncture with 10-year risk calculation largely driven by age, would increase pharmacological treatment preferentially in very old individuals, while increasing prevalence and uncontrolled rate mostly in younger subgroups. Adoption of lower BP cutoff to the KSH guideline would require validated cardiovascular disease risk assessment tools accounting for risk distributions specific to Korean population., Competing Interests: The authors have no financial conflicts of interest., (Copyright © 2020. The Korean Society of Cardiology.)

Background: Dyslipidemia is a multifactorial disorder, which arises from complex interactions among genetic and environmental risk factors. Previous studies have established the deteriorating effect of aging on lipid profiles. However, little is known about the role of education level, a stable marker of socioeconomic status, which reflect modifiability of lifestyle risk factors. Therefore, we examined the association between age and individual dyslipidemia parameter across education level among healthy, middle-aged Korean women., Methods: From 2049 middle-aged women, education attainment was classified into completion of elementary school or below, middle school, high school, college or above. Dyslipidemia was assessed in adherence to the 2018 Korean Dyslipidemia Treatment Guideline. Multivariable logistic regression and generalized linear model tested for associations between age and dyslipidemia parameter across education level and other known risk factors, including menopause, obesity, and current drinking and smoking., Results: In this cross-sectional analysis, the prevalence of each dyslipidemia parameter was significantly different by age and education level. The odds ratio (OR) for dyslipidemia was higher among participants who were older and had received higher education (OR = 2.31, p for interaction = 0.008) than younger and low education counterpart. The interaction between age and education level remained significant for hypercholesterolemia (p for interaction = 0.003) and hyper-LDL-cholesterolemia (p for interaction = 0.002)., Conclusions: Separate examination of individual dyslipidemia parameter indicated varying degree of interaction with age and education level. Such results imply that each type of lipid abnormality may arise from and be exacerbated by heterogeneous composition of biological and lifestyle risk factors, which may be reflected by education level.

Objectives: Physical activity (PA) is an established protective factor for many chronic diseases. Numerous studies have established positive relationships between social networks and PA. Accordingly, this study examined the relationship between social network structures (specifically the network size and the number and proportion of same-sex alters) and self-reported PA in Korean middle-age adults, where the term "alter" refers to a respondent's social network members., Methods: We analyzed 8,092 participants of the Cardiovascular and Metabolic Diseases Etiology Research Center cohort. We assessed the association between each network structure variable and PA level using a linear regression model. Then, we employed logistic regression to evaluate associations between social network structure and adherence to guideline-recommended exercise levels. Socio-demographic factors and health status measures were used as covariates., Results: In both sexes, the social network size and proportion of same-sex network members showed positive relationships with total and moderate-to-vigorous PA. Notably, female participants with a greater number of kin were more likely to satisfy the recommended amount of total PA., Conclusions: These findings suggest that large scale, same-sex intervention programs can help to achieve recommended PA regimens.

Background: The significance of high systolic and diastolic blood pressure remains controversial. We assessed the differences in prevalence of hypertension and its subtypes according to the different hypertension diagnostic criteria embodied by the 2017 American College of Cardiology/American Heart Association (2017 ACC/AHA) and 2018 Korean Society of Hypertension (2018 KSH) guidelines., Methods: We used the 2007-2017 Korea National Health and Nutrition Examination Survey (KNHANES) data to calculate guideline-specific hypertension prevalence among untreated, adult participants. By the 2017 ACC/AHA guideline, a mean SBP ≥130 mmHg, DBP ≥80 mmHg, or currently using antihypertensive medications were considered to have hypertension. Isolated diastolic hypertension (IDH) was defined as DBP ≥80 mmHg and SBP <130 mmHg, isolated systolic hypertension (ISH) as SBP ≥130 mmHg and DBP <80 mmHg, and systolic diastolic hypertension (SDH) as SBP ≥130 mmHg and DBP ≥80 mmHg. In a similar manner, by the 2018 KSH guideline, all hypertension and its subtype prevalence were calculated using the 140/90 mmHg cutoff. The two versions of all hypertension and its corresponding subtype prevalence were calculated among all study participants and separately by sex and age then compared via analysis of variance., Results: The prevalence of all hypertension increased from 25.9% (95% confidence interval (CI) 25.4-26.5) defined by the 2018 KSH guideline to 46.3% (95% CI 45.6-46.9) classified by the 2017 ACC/AHA guideline. Such increase was primarily manifested through substantial increase in IDH prevalence, from 5.2% (95% CI 4.9-5.4) defined by the 2018 KSH guideline to 17.9% (95% CI 17.4-18.3) defined by the 2017 ACC/AHA guideline, and was most notably observed in young age groups, 30-49 years. ISH prevalence showed minimal differences. SDH prevalence moderately increased from 3.5% (95% CI 3.3-3.7) defined by the 2018 KSH guideline to 11.1% (95% CI 10.7-11.4) defined by the 2017 ACC/AHA guideline, achieved primarily among participants aged 50 years or above., Conclusions: Changes in each subtype prevalence made differential contribution to additionally classified hypertension cases by the 2017 ACC/AHA guideline. Future studies should investigate the diastolic-associated cardiovascular risks and benefits of its long-term primary prevention in the young population., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s). 2019.)

Objectives: The relationships among discrimination, social support, and mental health have mostly been studied in minorities, and relevant studies in the general population are lacking. We aimed to investigate associations between discrimination and depressive symptoms in Korean non-minority young adults, considering the role of social support., Methods: In total, 372 participants who completed the psychological examinations conducted in the third wave of the Jangseong High School Cohort study were included. We used the Everyday Discrimination Scale to evaluate perceived discrimination and the Beck Depression Inventory-II to measure depressive symptoms. Social support was measured by the Multidimensional Scale of Perceived Social Support. Multivariate linear regression was conducted to investigate associations between discrimination and depression, along with the effect modification of social support. We stratified the population by gender to investigate gender differences., Results: Perceived discrimination was significantly associated with depressive symptoms (β=0.736, p&lt;0.001), and social support was negatively associated with depression (β=-0.245, p&lt;0.001). In men, support from friends was the most influential factor (β=-0.631, p=0.011), but no significant effect modification was found. In women, support from family was the most influential factor (β=-0.440, p=0.010), and women with higher familial support showed a significantly diminished association between discrimination and depression, unlike those with lower family support., Conclusions: Discrimination perceived by individuals can lead to depressive symptoms in Korean young adults, and this relationship can may differ by gender and social support status.

Background and Objectives: Discrepancy in blood pressure (BP) control rate may be owed to different risk factors associated with elevated systolic and diastolic BP (SBP and DBP)., Methods: In a nationally representative survey of Korean population with BP measurements, a total of 5,100 participants with hypertension was included in the analyses. Three separate types of control rates were calculated: SBP, DBP, and (combined) S&DBP among all participants with hypertension and participants with treated hypertension, separately. Control rates were compared across sex and age groups. Multivariable logistic regression was used to identify demographic factors associated with SBP, DBP, and S&DBP control rates, separately., Results: In total, SBP, DBP, and S&DBP control rates were 63.0%, 63.7%, and 42.5% among all hypertension patients, and 77.5%, 87.4%, and 71.6% among treated hypertension patients. Men aged 40-49 years with hypertension and 30-39 years treated for hypertension had the highest SBP control rate (74.6% and 96.2%), which decreased by older age. Inversely, DBP control rate progressively increased with older age. SBP control rate among women with hypertension was the highest in 40-49 years (67.0%) but without linear trend by age group. Interestingly, both combined and DBP control rates were noticeably low among women aged 50-59 years. Women with body mass index ≥25 were at higher odds of having controlled SBP. Lower DBP control rate was observed in men with lower education level, higher household income, and heavy drinkers., Conclusions: Separate examination of control rates demonstrated different sex- and age-differential trends, which would have been overlooked in combined control rates., Competing Interests: The authors have no financial conflicts of interest., (Copyright © 2019. The Korean Society of Cardiology.)

The 2017 American College of Cardiology/American Heart Association (ACC/AHA) high blood pressure (BP) guideline lowered the cut-off for hypertension, but its age-specific association with cardiovascular disease (CVD) remains inconclusive in different populations. We evaluated the association between high BP according to the 2017 ACC/AHA guideline and CVD risks in Koreans aged 20-94 years. In a nationwide health screening cohort, we included 15,508,537 persons aged 20-94 years without prior CVD. BP was categorized into normal, elevated, stage 1 hypertension, or stage 2 hypertension. The primary outcome was a composite CVD hospitalization (myocardial infarction, stroke, and/or heart failure). Over 10 years of follow-up, CVD incidence rates per 100,000 person-years were 105.4, 168.3, 215.9, and 641.2 for normal, elevated BP, stage 1, and stage 2 hypertension, respectively. The age-specific hazard ratios of stage 1 hypertension compared to normal BP were 1.41 (1.34-1.48) at ages 20-34, 1.54 (1.51-1.57) at ages 35-49, 1.38 (1.35-1.40) at ages 50-64, 1.21 (1.19-1.24) at ages 65-79, and 1.11 (1.03-1.19) at ages 80-94 years. With the lowered BP cut-off, 130/80 mmHg, population attributable fraction for CVD was 32.2%. In conclusion, stage 1 hypertension was significantly associated with a higher CVD risk across entire adulthood. The new definition of hypertension may have a substantial population impact on primary CVD prevention., Competing Interests: The authors declare no conflicts of interest.

Introduction: The association of suicide with the use of oral contraceptives (OC) is unknown in the Asian population. We aimed to evaluate the association of OC use and suicidal behavior in a nationally representative population of Korean women., Method: Of the 44,501 women who participated in the Korea National Health and Nutrition Examination Survey (KNHANES) (2007-2016), 27,067 women aged 20 years or older who had completed information on OC use and suicidal behavior were included. Women with a history of cancer were excluded. Compared to non-users of OC, odds ratios (ORs) for suicide attempt/ideation were calculated using a multivariable logistic regression among OC users, with testing of the interaction term of OC use and history of depression. We also conducted a stratified analysis by history of depression., Results: A total of 4,067 women (14.0%) reported they had suicide ideations or had attempted suicide, respectively. OC use was associated with an increased prevalence of suicidality (OR = 1.13, 95% CI 1.00-1.24) after adjustments for age, demographic factors, age of menarche, and lifestyle behaviors. When stratified by history of depression diagnosis, ORs linearly increased as the total duration of OC use lengthened among women with a history of depression; however, women without a history of depression showed peaked OR at 4- to 12-month use., Conclusion: There is an increased association between OC use and suicidality and the pattern of the relationship differs depending on whether there is a history of depression., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objectives: Previous studies have shown relatively low correlations between self-reported and accelerometer-assessed physical activity (PA). However, this association differs by socio-demographic factors, and this relationship has not been fully investigated in the general population. Thus, we investigated the correlation between self-reported and accelerometer-assessed PA and whether it differed by demographic and socioeconomic factors among the Korean general population., Methods: This cross-sectional study included 623 participants (203 men and 420 women) aged 30 to 64 years, who completed a PA questionnaire and wore a wrist-worn accelerometer on the non-dominant wrist for 7 days. We examined the agreement for metabolic equivalent task minutes per week (MET-min/wk) between the 2 measures and calculated Spearman correlation coefficients according to demographic and socioeconomic factors., Results: The kappa coefficient between tertiles of self-reported and accelerometer-assessed total MET-min/wk was 0.16 in the total population, suggesting overall poor agreement. The correlation coefficient between the 2 measurements was 0.26 (p<0.001) in the total population, and the correlation tended to decrease with increasing age (p for trend <0.001) and depression scores (p for trend <0.001)., Conclusions: We found a low correlation between self-reported and accelerometer-assessed PA among healthy Korean adults, and the correlation decreased with age and depression score. When studying PA using accelerometers and/or questionnaires, age and depression need to be considered, as should differences between self-reported and accelerometer-assessed PA.