Levels of Systolic and Diastolic Blood Pressure and Their Relation to Incident Metabolic Syndrome

Cardiology ◽  
2019 ◽  
Vol 142 (4) ◽  
pp. 224-231 ◽  
Author(s):  
Ju Young Jung ◽  
Chang-Mo Oh ◽  
Joong-Myung Choi ◽  
Jae-Hong Ryoo ◽  
Pil-Wook Chung ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Metabolic Syndrome ◽  
Subgroup Analysis ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Predictive Ability ◽  
Heart Association ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
The Metabolic Syndrome

Background: Elevated blood pressure (BP) is a component of the metabolic syndrome (MetS), and one third of individuals with hypertension simultaneously have MetS. However, the evidence is still unclear regarding the predictive ability of BP for incident MetS. Methods: In total, 5,809 Koreans without baseline MetS were grouped by baseline systolic (SBP) and diastolic BP (DBP) and monitored for 10 years to identify incident MetS. A Cox proportional hazards model was used to evaluate the HR and 95% CI for MetS according to SBP and DBP. Subgroup analysis was conducted in the normotensive population based on a new guideline of the American College of Cardiology and the American Heart Association. Results: High-BP groups tended to have worse metabolic profiles than the lowest-BP group in both SBP and DBP categories. In all of the participants, elevated SBP and DBP levels were significantly associated with the increased HR for MetS, even after adjusting for covariates. Subgroup analysis for normotensive participants indicated that the HR for MetS increased proportionally to both SBP (<110 mm Hg: reference, 110–119 mm Hg: HR = 1.60 [95% CI 1.40–1.84], and 120–129 mm Hg: HR = 2.12 [95% CI 1.82–2.48]) and DBP levels (<70 mm Hg: reference, 71–74 mm Hg: HR = 1.31 [95% CI 1.09–1.58], and 75–79 mm Hg: HR = 1.51 [95% CI 1.25–1.81]). Conclusion: The risk of incident MetS increased proportionally to baseline SBP and DBP, and this was identically observed even in normotensive participants.

scholarly journals Changes in Metabolic Syndrome Status and Risk of Dementia

2020 ◽  
Vol 9 (1) ◽  
pp. 122 ◽  
Author(s):  
Ji Eun Lee ◽  
Dong Wook Shin ◽  
Kyungdo Han ◽  
Dahye Kim ◽  
Jung Eun Yoo ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Blood Pressure ◽  
Alzheimer's Disease ◽  
Metabolic Syndrome ◽  
Vascular Dementia ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Screening Program ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model

This study investigated the effects of changes in metabolic syndrome (MS) status and each component on subsequent dementia occurrence. The study population was participants of a biennial National Health Screening Program in 2009–2010 and 2011–2012 in Korea. Participants were divided into four groups according to change in MS status during the two-year interval screening: sustained normal, worsened (normal to MS), improved (MS to normal), and sustained MS group. Risk of dementia among the groups was estimated from the second screening date to 31 December 2016 using a Cox proportional hazards model. A total of 4,106,590 participants were included. The mean follow-up was 4.9 years. Compared to the sustained normal group, adjusted hazard ratios (aHR) (95% confidence interval) were 1.11 (1.08–1.13) for total dementia, 1.08 (1.05–1.11) for Alzheimer’s disease, and 1.20 (1.13–1.28) for vascular dementia in the worsened group; 1.12 (1.10–1.15), 1.10 (1.07–1.13), and 1.19 (1.12–1.27) for the improved group; and 1.18 (1.16–1.20), 1.13 (1.11–1.15), and 1.38 (1.32–1.44) for the sustained MS group. Normalization of MS lowered the risk of all dementia types; total dementia (aHR 1.18 versus 1.12), Alzheimer’s disease (1.13 versus 1.10), and vascular dementia (1.38 versus 1.19). Among MS components, fasting glucose and blood pressure showed more impact. In conclusion, changes in MS status were associated with the risk of dementia. Strategies to improve MS, especially hyperglycemia and blood pressure, may help to prevent dementia.

Effects of Azacitidine (AZA) Vs Conventional Care Regimens (CCR) in Elderly (≥75 years) Patients (Pts) with Myelodysplastic Syndromes (MDS) from the AZA-001 Survival Trial

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3629-3629 ◽  
Author(s):  
John F Seymour ◽  
Pierre Fenaux ◽  
Lewis B. Silverman ◽  
Ghulam J Mufti ◽  
Eva Hellström-Lindberg ◽  
...  
Keyword(s):  
Active Treatment ◽  
Subgroup Analysis ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Performance Status ◽  
Treatment Options ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Phase Iii ◽  
Risk Of Death

Abstract Background. A recent phase III trial (AZA-001) showed AZA is the first treatment to significantly extend overall survival (OS) in higher-risk MDS patients (pts) (Blood2007;110:817). MDS incidence increases with age resulting in limited treatment options, particularly for those ≥75 years of age, given the poor tolerability and ineffectiveness of cytotoxic therapies. This subgroup analysis compared the effects of AZA vs CCR on OS, hematologic improvement (HI), transfusion independence (TI), and tolerability in pts ≥75 yrs of age. Methods. Higher-risk MDS (FAB: RAEB, RAEB-T, CMML and IPSS: Int-2 or High) pts were enrolled. All pts were pre-selected by site investigators – based on age, performance status, and comorbidities – to receive 1 of 3 CCR: best supportive care only (BSC); lowdose ara-C (LDAC), or intensive chemotherapy (IC). Pts were then randomized to AZA (75 mg/m2/d SC × 7d q 28d), or to CCR. Those randomized to AZA received AZA; those randomized to CCR received their pre-selected treatment. Randomization was stratified based on FAB subtype (RAEB and RAEB-T) and IPSS (Int-2 or High). Erythropoiesis stimulating agents were disallowed. OS was assessed using Kaplan-Meier (KM) methods and HI and TI were assessed per IWG 2000. To adjust for baseline imbalances, a Cox proportional hazards model was used, with ECOG status, LDH, number of RBC transfusions, Hgb, and presence or absence of -7/del(7q) at baseline as variables in the final model. Adverse events (AEs) were evaluated using NCI-CTC v. 2.0. Results. Of all enrolled pts (N=358, median age 69 yrs), 87 pts (24%) were ≥75 yrs of age (AZA n=38, CCR n=49 [BSC, n=33; LDAC, n=14; IC, n=2]). The majority of pts randomized to CCR received BSC only, suggesting clinicians are generally reticent to use active treatment in this population. Similar to the overall AZA-001 results, treatment with AZA was associated with prolonged survival in pts ≥75 yrs of age, with KM median OS in the AZA group not reached at 17.7 months of follow-up, vs KM median OS for CCR at 10.8 months (HR: 0.48 [95%CI: 0.26, 0.89]; p=0.0193). In these pts, OS rates at 2 years were significantly higher in the AZA group vs CCR: 55% vs 15% (p=0.0003). Two-fold more RBC transfusion-dependent pts at baseline in the AZA group achieved TI vs CCR: 10/23 (44%) vs 7/32 (22%), p=0.1386, respectively. Similarly, more pts in the AZA group achieved HI (major + minor) vs CCR: 58% vs 39%, (p=0.0875), respectively. As previously reported, AZA was generally well tolerated. Anemia, neutropenia, and thrombocytopenia were seen in 42%, 66%, and 71% of pts in the AZA group, respectively, vs 47%, 26%, and 40% in the CCR group, who were predominately receiving BSC only. Infections were reported by 79% and 60% of AZA and CCR pts, respectively. Discontinuations due to an AE occurred in 13% of AZA and 8% of CCR pts ≥75 yrs of age. Conclusion. Data from this subgroup analysis indicate pts ≥75 yrs of age with higher-risk MDS receiving active treatment with AZA experience significantly prolonged 2-year OS and reduced risk of death. AZA is generally well tolerated in this elderly patient population.

scholarly journals Time Scales in Epidemiological Analysis: An Empirical Comparison

2016 ◽  
Vol 5 (3) ◽  
pp. 91 ◽  
Author(s):  
Prabhakar Chalise ◽  
Eric Chicken ◽  
Daniel McGee
Keyword(s):  
Time Scales ◽  
Time Scale ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Predictive Ability ◽  
Observation Time ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Empirical Examination ◽  
Hazards Model

The Cox proportional hazards model is routinely used to analyze time-to-event data. This model requires the definition of a unique well-defined time scale. Most often, observation time is used as the time scale for both clinical and observational studies. Recently after a suggestion that it may be a more appropriate scale, chronological age has begun to appear as the time scale used in some reports. There appears to be no general consensus about which time scale is appropriate for any given analysis. It has been suggested that if the baseline hazard is exponential or if the age-at-entry is independent of covariates used in the model, then the two time scales provide similar results. In this report we provide an empirical examination of the results using the two different time scales using a large collection of data sets to examine the relationship between systolic blood pressure and coronary heart disease death. We demonstrate, in this empirical example that the two time-scales can sometimes lead to differing regression coefficient estimates but time-on-study model has better predictive ability in general.

scholarly journals Ambulatory blood pressure profile and stroke recurrence

2021 ◽  
pp. svn-2020-000526
Author(s):  
Jie Xu ◽  
Fei Jiang ◽  
Anxin Wang ◽  
Hui Zhi ◽  
Yuan Gao ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Ambulatory Blood Pressure ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Pressure Profile ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Stroke Recurrence ◽  
Hazards Model ◽  
Significant Difference

ObjectivesTo establish a new ambulatory blood pressure (ABP) parameter (24-hour ABP profile) and evaluated its performance on stroke outcome in ischaemic stroke (IS) or transient ischaemic attack (TIA) patients.MethodsThe prospective cohort consisted of 1996 IS/TIA patients enrolled for ABP monitoring and a 3-month follow-up for stroke recurrence as outcome. Profile groups of systolic blood pressure (SBP) were identified via an advanced functional clustering method, and the associations of the profile groups and conventional ABP parameters with stroke recurrence were examined in a Cox proportional hazards model.ResultsThree discrete profile groups (n=604, 781 and 611 in profiles 1, 2 and 3, respectively) in 24-hour ambulatory SBP were identified. Profile 1 resembled most to the normal diurnal blood pressure pattern; profile 2 also dropped at night, but climbed earlier and with higher morning surge; while profile 3 had sustained higher nocturnal SBP without significant nocturnal SBP decline. The incidence of stroke recurrence was 2.9%, 3.9% and 5.5% in profiles 1, 2 and 3, respectively. After adjustment for covariates, profile 3 was significantly associated with higher risk of stroke recurrence with profile 1 as reference (HR 1.76, 95% CI: 1.00 to 3.09), while no significant difference was observed between profiles 2 and 1 (HR 1.22, 95% CI: 0.66 to 2.25). None of conventional ABP parameters showed significant associations with the outcome.ConclusionsAmbulatory 24-hour SBP profile is associated with short-term stroke recurrence. Profiles of ABP may help improve identification of stroke recurrence by capturing the additive effects of individual ABP parameters.

scholarly journals Glucocorticoid use is associated with an increased risk of hypertension

Rheumatology ◽  
2020 ◽  
Vol 60 (1) ◽  
pp. 132-139
Author(s):  
Ruth E Costello ◽  
Belay B Yimer ◽  
Polly Roads ◽  
Meghna Jani ◽  
William G Dixon
Keyword(s):  
Blood Pressure ◽  
Cumulative Dose ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Practice Research ◽  
Clinical Practice Research Datalink ◽  
Incident Hypertension ◽  
Increased Risk

Abstract Objectives Patients with RA are frequently treated with glucocorticoids (GCs), but evidence is conflicting about whether GCs are associated with hypertension. The aim of this study was to determine whether GCs are associated with incident hypertension in patients with RA. Methods A retrospective cohort of patients with incident RA and without hypertension was identified from UK primary care electronic medical records (Clinical Practice Research Datalink). GC prescriptions were used to determine time-varying GC use, dose and cumulative dose, with a 3 month attribution window. Hypertension was identified through either: blood pressure measurements &gt;140/90 mmHg, or antihypertensive prescriptions and a Read code for hypertension. Unadjusted and adjusted Cox proportional hazards regression models were fitted to determine whether there was an association between GC use and incident hypertension. Results There were 17 760 patients in the cohort. A total of 7421 (42%) were prescribed GCs during follow-up. The incident rate of hypertension was 64.1 per 1000 person years (95% CI: 62.5, 65.7). The Cox proportional hazards model indicated that recent GC use was associated with a 17% increased hazard of hypertension (hazard ratio 1.17; 95% CI: 1.10, 1.24). When categorized by dose, only doses above 7.5 mg were significantly associated with hypertension. Cumulative dose did not indicate a clear pattern. Conclusion Recent GC use was associated with incident hypertension in patients with RA, in particular doses ≥7.5 mg were associated with hypertension. Clinicians need to consider cardiovascular risk when prescribing GCs, and ensure blood pressure is regularly monitored and treated where necessary.

scholarly journals P1148THE ASSOCIATION WITH LOWER SYSTOLIC BLOOD PRESSURE AND ALL-CAUSE MORTALITY IN PATIENTS UNDERGOING PERITONEAL DIALYSIS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Motoyasu Kurahashi ◽  
Kenji Harada ◽  
Hidetoshi Kanai
Keyword(s):  
Blood Pressure ◽  
Multivariate Analysis ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Group 4 ◽  
Hazards Model ◽  
All Cause Mortality ◽  
Composite Events

Abstract Background and Aims Previous observational studies have been reported that a U-shaped association between systolic blood pressure (SBP) and mortality in patients undergoing hemodialysis. However, the optimal blood pressure in patients undergoing peritoneal dialysis (PD) remains unclear. Method The present study is observational and conducted in a single center. Four hundred and sixteen patients undergoing PD managed in our hospital from April 2010 to December 2017 were participated in this study. The patients were divided into four groups depended on office SBPs, as follows; group1: SBP &lt;110 mmHg (n=60), group2: SBP 110-139 mmHg (n=187), group3: SBP 140-159 mmHg (n=113) and group4: SBP ≧160 mmHg (n=56). When using the Cox proportional hazards model, group 2 was regarded as a reference. Hypertension was defined as SBP ≧140 mmHg, diastolic blood pressure ≧90 mmHg, or use of any anti-hypertensive drugs. The association between SBP with several outcomes such as the risk of all-cause deaths, cardiovascular events and these composite events were estimated using cox proportional hazards model. Adjusted factors were age, sex, comorbidities, laboratory covariates, left ventricle ejection fraction and medications such as renin-angiotensin system blockades and statins. Results The mean follow-up period was 29.2 months. The prevalence of hypertension was 90.4% (n=376) of all patients. The risk of all-cause deaths with multivariate cox proportional hazards regression analysis was significantly higher in the group 1 (hazard ratio 2.08, 95% CI 1.23-3.51, p=0.006). While the risk of CV events with univariate analysis tended to be higher in group 4, there was no significant association between SBP and the risk of CV events with multivariate analysis. The risk of the composite events with multivariate analysis was significantly higher in group 4 (hazard ratio 1.61, 95% CI 1.01-2.57, p=0.047). Conclusion This study indicated that lower SBP was independently associated with all-cause mortality in patients undergoing PD. Moreover, higher SBP might be involved with composite events.

scholarly journals Grain Subtype and the Combination of Grains Consumed Are Associated with the Risk of Metabolic Syndrome: Analysis of a Community-Based Prospective Cohort

2019 ◽  
Vol 150 (1) ◽  
pp. 118-127 ◽  
Author(s):  
Yunhee Kang ◽  
Kyueun Lee ◽  
Jieul Lee ◽  
Jihye Kim
Keyword(s):  
Metabolic Syndrome ◽  
Prospective Cohort ◽  
Lower Risk ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Whole Grains ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Community Based ◽  
Refined Grains

ABSTRACT Background Evidence on the prospective association between grain consumption and metabolic syndrome (MetS) is lacking. Objective This study explored the association between grain intake by subtype or various combinations of grain intake and the risk of developing MetS in South Korean adults using data from a community-based prospective cohort study. Methods A total of 5717 participants (2984 men and 2733 women) aged 40–69 y without MetS were followed up for 10 y (2001–2012). Grain consumption was assessed using a semiquantitative FFQ at baseline (2001–2002) and a follow-up examination (2005–2006). A multivariate Cox proportional hazards model was used to examine the risk of incident MetS and its components according to grain consumption (&lt;1, 1 to &lt;3, or ≥3 servings/d) by sex. Results In total, 2218 participants (38.8%) developed MetS. Frequent consumers of whole grains (≥3 servings/d) had a lower risk of incident MetS (men—HR: 0.51; 95% CI: 0.41, 0.63; P  = 0.0001; women—HR: 0.73; 95% CI: 0.60, 0.90; P = 0.0029), whereas frequent consumers of refined grains had a higher risk of incident MetS (men—HR: 1.63; 95% CI: 1.31, 2.03; P &lt; 0.0001; women—HR: 2.25; 95% CI: 1.82, 2.78; P &lt; 0.0001) compared with rare consumers (&lt;1 serving/d). The combination of low whole grains (&lt;2 servings/d) and high refined grains (≥2 servings/d) was associated with a higher risk of MetS than the combination of high whole grains and low refined grains (men—HR: 1.21; 95% CI: 1.04, 1.41; P = 0.012; women—HR: 1.43; 95% CI: 1.23, 1.66; P &lt; 0.0001). Conclusions Higher consumption of whole grains was associated with lower risk of incident MetS, whereas higher refined-grain consumption was associated with a higher risk in a middle-aged and older Korean population.

scholarly journals Pentraxin-3 Predicts Long-Term Cardiac Events in Patients with Chronic Heart Failure

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Haibo Liu ◽  
Xiaofang Guo ◽  
Kang Yao ◽  
Chunming Wang ◽  
Guozhong Chen ◽  
...  
Keyword(s):  
Heart Failure ◽  
Chronic Heart Failure ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Heart Association ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Pentraxin 3 ◽  
Cardiac Events

The aim of this study was to investigate the long-term prognostic value of pentraxin-3 (PTX3) in patients with chronic heart failure (CHF). 377 patients were prospectively followed up for 3 years to determine cardiac events including cardiac death or rehospitalization for worsening heart failure. The plasma PTX3 levels were significantly higher in CHF patients than in healthy subjects (p<0.001), and they increased with advancing New York Heart Association (NYHA) Functional Classification (p<0.001). Plasma PTX3 levels in CHF patients with cardiac events were significantly higher than in event-free patients (p<0.001). We determined the normal upper limit of plasma PTX3 levels from the mean + 2 SD value of 64 control subjects (3.64 ng/mL). A Kaplan-Meier analysis revealed that patients with increased PTX3 (≥3.64 ng/mL) were at a higher risk for cardiac events than those without increased PTX3 (p<0.01). A multifactorial Cox proportional hazards model showed that increased PTX3 (≥3.64 ngImL) was an independent risk factor for cardiac events in CHF patients (hazard ratio (HR) = 4.224,p<0.01; 95% CI: 1.130–15.783). Plasma PTX3 levels are a long-term independent predictor of prognosis in patients with CHF.

scholarly journals Emergency department crowding and mortality in 14 Swedish emergency departments, a cohort study leveraging the Swedish Emergency Registry (SVAR)

PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0247881
Author(s):  
Björn af Ugglas ◽  
Per Lindmarker ◽  
Ulf Ekelund ◽  
Therese Djärv ◽  
Martin J. Holzmann
Keyword(s):  
Emergency Department ◽  
Cohort Study ◽  
Subgroup Analysis ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
National Registry ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Multicenter Studies ◽  
Ed Crowding

Objectives There is evidence that emergency department (ED) crowding is associated with increased mortality, however large multicenter studies of high quality are scarce. In a prior study, we introduced a proxy-measure for crowding that was associated with increased mortality. The national registry SVAR enables us to study the association in a more heterogenous group of EDs with more recent data. The aim is to investigate the association between ED crowding and mortality. Methods This was an observational cohort study including visits from 14 EDs in Sweden 2015–2019. Crowding was defined as the mean ED-census divided with expected ED-census during the work-shift that the patient arrived. The crowding exposure was categorized in three groups: low, moderate and high. Hazard ratios (HR) for mortality within 7 and 30 days were estimated with a cox proportional hazards model. The model was adjusted for age, sex, triage priority, arrival hour, weekend, arrival mode and chief complaint. Subgroup analysis by county and for admitted patients by county were performed. Results 2,440,392 visits from 1,142,631 unique patients were analysed. A significant association was found between crowding and 7-day mortality but not with 30-day mortality. Subgroup analysis also yielded mixed results with a clear association in only one of the three counties. The estimated HR (95% CI) for 30-day mortality for admitted patients in this county was 1.06 (1.01–1.12) in the moderate crowding category, and 1.11 (1.01–1.22) in the high category. Conclusions The association between crowding and mortality may not be universal. Factors that influence the association between crowding and mortality at different EDs are still unknown but a high hospital bed occupancy, impacting admitted patients may play a role.

scholarly journals Evaluation of the association between periodontitis and risk of Parkinson’s disease: a nationwide retrospective cohort study

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Eunkyung Jeong ◽  
Jun-Beom Park ◽  
Yong-Gyu Park
Keyword(s):  
Parkinson’S Disease ◽  
Metabolic Syndrome ◽  
Parkinson's Disease ◽  
South Korea ◽  
Large Scale ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Population Based ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model

AbstractThe objective of this study was to examine the association between periodontitis and risk of incident Parkinson’s disease using large-scale cohort data on the entire population of South Korea. Health checkup data from 6,856,180 participants aged 40 and older were provided by the National Health Insurance Service of South Korea between January 1, 2009, and December 31, 2009, and the data were followed until December 31, 2017. The hazard ratio (HR) of Parkinson’s disease and 95% confidence interval (CI) were estimated using a Cox proportional hazards model adjusted for potential confounders. The incidence probability of Parkinson’s disease was positively correlated with the presence of periodontitis. The HR of Parkinson’s disease for the participants without the need of further dentist visits was 0.96 (95% CI 0.921–1.002); the HR of Parkinson’s disease increased to 1.142 (95% CI 1.094–1.193) for the individuals who needed further dentist visits. Compared to individuals without periodontitis and without metabolic syndrome, the HR of incident Parkinson’s disease gradually increased for individuals with periodontitis, with metabolic syndrome, and with both periodontitis and metabolic syndrome. People with periodontitis and metabolic syndrome had the highest HR of incident Parkinson’s disease, at 1.167 (95% CI 1.118–1.219). In conclusion, a weak association between periodontitis and Parkinson’s disease was suggested after adjusting for confounding factors from the population-based large-scale cohort of the entire South Korean population.

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