Thromboembolism after coronavirus disease 2019 vaccination in atrial fibrillation/flutter: a self-controlled case series study.

BACKGROUND AND AIMS: Concerns about the safety of coronavirus disease 2019 (COVID-19) vaccines in patients with atrial fibrillation/flutter (AF/AFL) have arisen due to reports of thrombo-embolic events following COVID-19 vaccination in the general population. This study aimed to evaluate the risk of thrombo-embolic events after COVID-19 vaccination in patients with AF/AFL. METHODS: This was a modified self-controlled case-series study using a comprehensive nationwide-linked database provided by the National Health Insurance Service in South Korea to calculate incidence rate ratios (IRRs) of thrombo-embolic events. The study population included individuals aged ≥12 years who were either vaccinated (e.g. one or two doses) or unvaccinated during the period from February to December 2021. The primary outcome was a composite of thrombo-embolic events, including ischaemic stroke, transient ischaemic attack, and systemic thromboembolism. The risk period was defined as 0-21 days following COVID-19 vaccination. RESULTS: The final analysis included 124 127 individuals with AF/AFL. The IRR of thrombo-embolic events within 21 days after COVID-19 vaccination, compared with that during the unexposed control period, was 0.93 [95% confidence interval (CI) 0.77-1.12]. No significant risk variations were noted by sex, age, or vaccine type. However, patients without anticoagulant therapy had an IRR of 1.88 (95% CI 1.39-2.54) following vaccination. CONCLUSIONS: In patients with AF/AFL, COVID-19 vaccination was generally not associated with an increased risk of thrombo-embolic events. However, careful individual risk assessment is required when advising vaccination for those not on oral anticoagulant, as these patients exhibited an increased risk of thrombo-embolic events post-vaccination.

Rationale, Design, and Interim Observations of the Steady Movement With Innovating Leadership for Heart Failure (SMILE HF) Registry: A Multicenter Prospective Cohort Registry for Patients With Acute Heart Failure.

Background and Objectives: Heart failure (HF) is a leading cause of hospitalization and death worldwide. The Steady Movement with Innovating Leadership for Heart Failure (SMILE HF) aims to evaluate the clinical characteristics, management, hospital course, and long-term outcomes of patients hospitalized for acute HF in South Korea. Methods: This prospective, observational multicenter cohort study was conducted on consecutive patients hospitalized for acute HF in nine university hospitals since September 2019. Enrolment of 2000 patients should be completed in 2024, and follow-up is planned through 2025. Results: Interim analysis of 1,052 consecutive patients was performed to understand the baseline characteristics. The mean age was 69±15 years; 57.6% were male. The mean left ventricular ejection fraction was 39±15%. The prevalences of HF with reduced ejection fraction, HF with mildly reduced ejection fraction, and HF with preserved ejection fraction were 50.9%, 15.3%, and 29.2%. Ischemic cardiomyopathy (CMP) was the most common etiology (32%), followed by tachycardia-induced CMP (12.8%) and idiopathic dilated CMP (9.5%). The prescription rate of angiotensin-converting enzyme inhibitor/angiotensin receptor blockers/angiotensin receptor/neprilysin inhibitor, beta-blockers, spironolactone, and sodium-glucose cotransporter-2 inhibitors at discharge were 76.8%, 66.5%, 50.0%, and 17.5%, respectively. The post-discharge 90-day mortality and readmission rates due to HF aggravation were 2.0% and 6.4%, respectively. Our analysis reveals the current state of acute HF in South Korea. Conclusions: Our interim analysis provides valuable insights into the clinical characteristics, management, and early outcomes of acute HF patients in South Korea, highlighting the current state and treatment patterns in this population.

Assessing lung fluid status using noninvasive bioelectrical impedance analysis in patients with acute heart failure: A pilot study.

BACKGROUND: Outpatient monitoring of pulmonary congestion in heart failure (HF) patients may reduce hospitalization rates. This study tested the feasibility of non-invasive high-frequency bioelectrical impedance analysis (HF-BIA) for estimating lung fluid status. METHODS: This prospective study included 70 participants: 50 with acute HF (HF group) and 20 without HF (control group). All participants underwent a supine chest CT scan to measure lung fluid content with lung density analysis software. Concurrently, direct segmental multi-frequency BIA was performed to assess the edema index (EI) of the trunk, entire body, and extremities. RESULTS: The correlation coefficients between lung fluid content and EI measured using HF-BIA were r = 0.566 (p < 0.001) and r = 0.550 (p < 0.001) for the trunk and whole body, respectively. In the HF group, the trunk EI (0.402 ± 0.015) and whole body EI (0.402 ± 0.016) were significantly higher than those of the control group (trunk EI, 0.383 ± 0.007; whole body EI, 0.383 ± 0.007; all p < 0.001). The lung fluid content was significantly higher in the HF than that in the control group (23.7 ± 5.3 vs. 15.5 ± 2.8%, p < 0.001). The log value of NT pro-BNP was significantly correlated with trunk EI (r = 0.688, p < 0.001) and whole-body EI (r = 0.675, p < 0.001) measured by HF-BIA, and the lung fluid content analyzed by CT (r = 0.686, p < 0.001). CONCLUSIONS: BIA-based EI measurements of the trunk and whole body significantly correlated with lung fluid content and NT pro-BNP levels. Non-invasive BIA could be a promising screening tool for lung fluid status monitoring in acute HF patients.

Effectiveness of a Smartphone App-Based Intervention With Bluetooth-Connected Monitoring Devices and a Feedback System in Heart Failure (SMART-HF Trial): Randomized Controlled Trial.

BACKGROUND: Current heart failure (HF) guidelines recommend a multidisciplinary approach, discharge education, and self-management for HF. However, the recommendations are challenging to implement in real-world clinical settings. OBJECTIVE: We developed a mobile health (mHealth) platform for HF self-care to evaluate whether a smartphone app-based intervention with Bluetooth-connected monitoring devices and a feedback system can help improve HF symptoms. METHODS: In this prospective, randomized, multicenter study, we enrolled patients 20 years of age and older, hospitalized for acute HF, and who could use a smartphone from 7 tertiary hospitals in South Korea. In the intervention group (n=39), the apps were automatically paired with Bluetooth-connected monitoring devices. The patients could enter information on vital signs, HF symptoms, diet, medications, and exercise regimen into the app daily and receive feedback or alerts on their input. In the control group (n=38), patients could only enter their blood pressure, heart rate, and weight using conventional, non-Bluetooth devices and could not receive any feedback or alerts from the app. The primary end point was the change in dyspnea symptom scores from baseline to 4 weeks, assessed using a questionnaire. RESULTS: At 4 weeks, the change in dyspnea symptom score from baseline was significantly greater in the intervention group than in the control group (mean -1.3, SD 2.1 vs mean -0.3, SD 2.3; P=.048). A significant reduction was found in body water composition from baseline to the final measurement in the intervention group (baseline level mean 7.4, SD 2.5 vs final level mean 6.6, SD 2.5; P=.003). App adherence, which was assessed based on log-in or the percentage of days when symptoms were first observed, was higher in the intervention group than in the control group. Composite end points, including death, rehospitalization, and urgent HF visits, were not significantly different between the 2 groups. CONCLUSIONS: The mobile-based health platform with Bluetooth-connected monitoring devices and a feedback system demonstrated improvement in dyspnea symptoms in patients with HF. This study provides evidence and rationale for implementing mobile app-based self-care strategies and feedback for patients with HF. TRIAL REGISTRATION: ClinicalTrials.gov NCT05668000; https://clinicaltrials.gov/study/NCT05668000.

Home Bioelectrical Impedance Analysis Management System in Patients With Heart Failure: Rationale and Study Design.

Body fluid monitoring and management are essential to control dyspnea and prevent re-hospitalization in patients with chronic heart failure (HF). There are several methods to estimate and monitor patient's volume status, such as symptoms, signs, body weight, and implantable devices. However, these methods might be difficult to use for reasons that are slow to reflect body water change, inaccurate in specific patients' condition, or invasive. Bioelectrical impedance analysis (BIA) is a novel method for body water monitoring in patients with HF, and the value in prognosis has been proven in previous studies. We aim to determine the efficacy and safety of home BIA body water monitoring-guided HF treatment in patients with chronic HF. This multi-center, open-label, randomized control trial will enroll patients with HF who are taking loop diuretics. The home BIA group patients will be monitored for body water using a home BIA device and receive messages regarding their edema status and direction of additional diuretics usage or behavioral changes through the linked application system once weekly. The control group patients will receive the usual HF management. The primary endpoint is the change in N-terminal prohormone of brain natriuretic peptide levels from baseline after 12 weeks. This trial will provide crucial evidence for patient management with a novel home BIA body water monitoring system in patients with HF.

Left ventricular global longitudinal strain as a prognosticator in hypertrophic cardiomyopathy with a low-normal left ventricular ejection fraction.

AIMS: The aim of this study was to investigate the prognostic utility of left ventricular (LV) global longitudinal strain (LV-GLS) in patients with hypertrophic cardiomyopathy (HCM) and an LV ejection fraction (LVEF) of 50-60%. METHODS AND RESULTS: This retrospective cohort study included 349 patients with HCM and an LVEF of 50-60%. The primary outcome was a composite of cardiovascular death, including sudden cardiac death (SCD) and SCD-equivalent events. The secondary outcomes were SCD/SCD-equivalent events, cardiovascular death (including SCD), and all-cause death. The final analysis included 349 patients (mean age 59.2 ± 14.2 years, men 75.6%). During a median follow-up of 4.1 years, the primary outcome occurred in 26 (7.4%), while the secondary outcomes of SCD/SCD-equivalent events, cardiovascular death, and all-cause death occurred in 15 (4.2%), 20 (5.7%), and 34 (9.7%), respectively. After adjusting for age, atrial fibrillation, ischaemic stroke, LVEF, and left atrial volume index, absolute LV-GLS (%) was independently associated with the primary outcome [adjusted hazard ratio (HR) 0.88, 95% confidence interval (CI) 0.788-0.988, P = 0.029]. According to receiver operating characteristic analysis, 10.5% is an optimal cut-off value for absolute LV-GLS in predicting the primary outcome. Patients with an absolute LV-GLS ≤ 10.5% had a higher risk of the primary outcome than those with an absolute LV-GLS > 10.5% (adjusted HR 2.54, 95% CI 1.117-5.787, P = 0.026). Absolute LV-GLS ≤ 10.5% was an independent predictor for each secondary outcome (P < 0.05). CONCLUSIONS: LV-GLS was an independent predictor of a composite of cardiovascular death, including SCD/SCD-equivalent events, in patients with HCM and an LVEF of 50-60%. Therefore, LV-GLS can help in risk stratification in these patients.

Development and validation of equation for cardiorespiratory fitness in patients with heart failure with preserved ejection fraction.

BACKGROUND/AIMS: Cardiorespiratory fitness (CRF), as measured by maximal oxygen consumption (VO2max), is an important independent predictive factor of cardiovascular outcomes in patients with heart failure (HF). However, it is unclear whether conventional equations for estimating CRF are applicable to patients with HF with preserved ejection fraction (HFpEF). METHODS: This study included 521 patients with HFpEF (EF ≥ 50%) whose CRF was directly measured by cardiopulmonary exercise test using a treadmill. We developed a new equation (Kor-HFpEF) for half of the patients in the HFpEF cohort (group A, n = 253) and validated it for the remaining half (group B, n = 268). The accuracy of the Kor-HFpEF equation was compared to that of the other equations in the validation group. RESULTS: In the total HFpEF cohort, the directly measured VO2max was significantly overestimated by the FRIEND and ACSM equations (p < 0.001) and underestimated by the FRIEND-HF equation (p <0.001) (direct 21.2 ± 5.9 mL/kg/min; FRIEND 29.1 ± 11.8 mL/kg/min; ACSM 32.5 ± 13.4 mL/kg/min; FRIEND-HF 14.1 ± 4.9 mL/kg/min). However, the VO2max estimated by the Kor-HFpEF equation (21.3 ± 4.6 mL/kg/min) was similar to the directly measured VO2max (21.7 ± 5.9 mL/kg/min, p = 0.124), whereas the VO2max estimated by the other three equations was still significantly different from the directly measured VO2max in group B (all p < 0.001). CONCLUSION: Traditional equations used to estimate VO2max were not applicable to patients with HFpEF. We developed and validated a new Kor-HFpEF equation for these patients, which had a high accuracy.

Korean vs. Western Exercise Capacity Nomograms for Korean Patients With Cardiovascular Disease.

BACKGROUND: Exercise capacity is known to be an independent predictor of cardiovascular events and mortality. However, most previous studies were based on Western populations. Further study is warranted for Asian patients according to ethnic or national standards. We aimed to compare prognostic values of Korean and Western nomograms for exercise capacity in Korean patients with cardiovascular disease (CVD). METHODS: In this retrospective cohort study, we enrolled 1,178 patients (62 ± 11 years; 78% male) between June 2015 and May 2020, who were referred for cardiopulmonary exercise testing in our cardiac rehabilitation program. The median follow-up period was 1.6 years. Exercise capacity was measured in metabolic equivalents by direct gas exchange method during the treadmill test. The nomogram for exercise capacity from healthy Korean individuals and a previous landmark Western study was used to determine the percentage of predicted exercise capacity. The primary endpoint was the composite of major adverse cardiovascular events (MACE; all-cause death, myocardial infarction, repeat revascularization, stroke and hospitalization for heart failure). RESULTS: A multivariate analysis showed that the risk of primary endpoint was more than double (hazard ratio [HR], 2.20; 95% confidence interval [CI], 1.10-4.40) in the patients with lower exercise capacity (< 85% of predicted) by Korean nomogram. The lower exercise capacity was one of the strong independent predictors along with left ventricular ejection fraction, age, and level of hemoglobin. However, the lower exercise capacity by Western nomogram could not predict the primary endpoint (HR, 1.33; 95% CI, 0.85-2.10). CONCLUSION: Korean patients with CVD with lower exercise capacity have higher risk of MACE. Considering inter-ethnic differences in cardiorespiratory fitness, the Korean nomogram provides more suitable reference values than the Western nomogram to determine lower exercise capacity and predict cardiovascular events in Korean patients with CVD.

Impact of drug-eluting stent-associated coronary artery spasm on 3-year clinical outcomes: A propensity score matching analysis.

BACKGROUND: It has been reported that significant endothelial dysfunction or clinically evident vasospasm can be associated with drug-eluting stents (DESs). However, the impact of DES associated coronary artery spasm (CAS) on long-term clinical outcomes has not been fully elucidated as compared with those of patients with vasospastic angina. METHODS: A total of 2797 consecutive patients without significant coronary artery lesion (<70%), who underwent the Acetylcholine (Ach) provocation test, were enrolled between Nov 2004 and Oct 2010. DES-associated spasm was defined as significant CAS in proximal or distal to previously implanted DES site at follow-up angiography with Ach test. Patients were divided into two groups (DES-CAS; n = 108, CAS; n = 1878). For adjustment, propensity score matching (PSM) was done (C-statistics = 0.766, DES-CAS; n = 102, CAS; n = 102). SPSS 20 (Inc., Chicago, Illinois) was used to analyze this data. RESULTS: Baseline characteristics were worse in the DES-CAS group. After PSM, both baseline characteristics and the Ach test results were balanced except higher incidence of diffuse CAS and ECG change in the DES-CAS group. During Ach test, the incidence of diffuse spasm (93.1% vs. 81.3%, p = 0.012) and ST-T change (10.7% vs. 1.9%, p = 0.010) were higher in the DES-CAS group. At 3-year, before and after adjustment, the DES-CAS group showed a higher incidence of coronary revascularization (9.8% vs. 0.0%, p = 0.001), recurrent chest pain requiring follow up coronary angiography (CAG, 24.5% vs. 7.8%, p = 0.001) and major adverse cardiac events (MACEs, 9.8% vs. 0.9%, p < 0.005). CONCLUSION: In this study, DES associated CAS was associated with higher incidence of diffuse spasm, ST-T change and adverse 3-year clinical outcomes. Special caution should be exercised in this particular subset of patients.

A Smartphone App (AnSim) With Various Types and Forms of Messages Using the Transtheoretical Model for Cardiac Rehabilitation in Patients With Coronary Artery Disease: Development and Usability Study.

BACKGROUND: Despite strong evidence of clinical benefit, cardiac rehabilitation (CR) programs are currently underutilized and smartphone-based CR strategies are thought to address this unmet need. However, data regarding the detailed process of development are scarce. OBJECTIVE: This study focused on the development of a smartphone-based, patient-specific, messaging app for patients who have undergone percutaneous coronary intervention (PCI). METHODS: The AnSim app was developed in collaboration with a multidisciplinary team that included cardiologists, psychiatrists, nurses, pharmacists, nutritionists, and rehabilitation doctors and therapists. First, a focus group interview was conducted, and the narratives of the patients were analyzed to identify their needs and preferences. Based on the results, health care experts and clinicians drafted messages into 5 categories: (1) general information regarding cardiovascular health and medications, (2) nutrition, (3) physical activity, (4) destressing, and (5) smoking cessation. In each category, 90 messages were developed according to 3 simplified steps of the transtheoretical model of behavioral change: (1) precontemplation, (2) contemplation and preparation, and (3) action and maintenance. After an internal review and feedback from potential users, a bank of 450 messages was developed. RESULTS: The focus interview was conducted with 8 patients with PCI within 1 year, and 450 messages, including various forms of multimedia, were developed based on the transtheoretical model of behavioral change in each category. Positive feedback was obtained from the potential users (n=458). The mean Likert scale score was 3.95 (SD 0.39) and 3.91 (SD 0.39) for readability and usefulness, respectively, and several messages were refined based on the feedback. Finally, the patient-specific message delivery system was developed according to the baseline characteristics and stages of behavioral change in each participant. CONCLUSIONS: We developed an app (AnSim), which includes a bank of 450 patient-specific messages, that provides various medical information and CR programs regarding coronary heart disease. The detailed process of multidisciplinary collaboration over the course of the study provides a scientific basis for various medical professionals planning smartphone-based clinical research.

Transcatheter Aortic Valve Replacement with Minimal Contrast Dye in Patients with Renal Insufficiency.

PURPOSE: Concerns have been consistently raised in regards to the considerable amount of contrast dye used during transcatheter aortic valve replacement (TAVR) in patients with renal insufficiency. In the present study, we introduced minimal contrast TAVR and compared its 30-day clinical outcomes with conventional TAVR. MATERIALS AND METHODS: We retrospectively investigated 369 patients who underwent TAVR between July 2011 and April 2020 in our institute. Among them, 93 patients with severe aortic stenosis and renal insufficiency (estimated glomerular filtration rate ≤50 mL/min/1.73 m²) were included and divided into a conventional TAVR group (n=56) and a minimal contrast TAVR group (n=37). In the minimal contrast TAVR group, the total amount of contrast was <10 mL during the entire TAVR procedure. Thirty-day major adverse clinical events (MACE), including death, stroke, implantation of permanent pacemaker, and initiation of hemodialysis, were investigated. RESULTS: The incidence of MACE was significantly lower in the minimal contrast TAVR group than the conventional TAVR group (16.2% vs. 42.9%, p=0.010). Death occurred in 9 patients (16.1%) in the conventional TAVR group and in 0 patients in the minimal contrast group (p=0.011). Hemodialysis was initiated in 2 patients (5.4%) in the minimal contrast TAVR group and in 7 patients (12.5%) in the conventional TAVR group (p=0.256). Multivariate regression analysis showed that the minimal contrast TAVR procedure was an independent predictor for reducing MACE (hazard ratio 0.208, 95% confidence interval: 0.080-0.541, p=0.001). CONCLUSION: Minimal contrast TAVR is feasible and shows more favorable short-term clinical outcomes than conventional TAVR in patients with renal insufficiency.

Macrophage targeted theranostic strategy for accurate detection and rapid stabilization of the inflamed high-risk plaque.

Rationale: Inflammation plays a pivotal role in the pathogenesis of the acute coronary syndrome. Detecting plaques with high inflammatory activity and specifically treating those lesions can be crucial to prevent life-threatening cardiovascular events. Methods: Here, we developed a macrophage mannose receptor (MMR)-targeted theranostic nanodrug (mannose-polyethylene glycol-glycol chitosan-deoxycholic acid-cyanine 7-lobeglitazone; MMR-Lobe-Cy) designed to identify inflammatory activity as well as to deliver peroxisome proliferator-activated gamma (PPARγ) agonist, lobeglitazone, specifically to high-risk plaques based on the high mannose receptor specificity. The MMR-Lobe-Cy was intravenously injected into balloon-injured atheromatous rabbits and serial in vivo optical coherence tomography (OCT)-near-infrared fluorescence (NIRF) structural-molecular imaging was performed. Results: One week after MMR-Lobe-Cy administration, the inflammatory NIRF signals in the plaques notably decreased compared to the baseline whereas the signals in saline controls even increased over time. In accordance with in vivo imaging findings, ex vivo NIRF signals on fluorescence reflectance imaging (FRI) and plaque inflammation by immunostainings significantly decreased compared to oral lobeglitazone group or saline controls. The anti-inflammatory effect of MMR-Lobe-Cy was mediated by inhibition of TLR4/NF-κB pathway. Furthermore, acute resolution of inflammation altered the inflamed plaque into a stable phenotype with less macrophages and collagen-rich matrix. Conclusion: Macrophage targeted PPARγ activator labeled with NIRF rapidly stabilized the inflamed plaques in coronary sized artery, which could be quantitatively assessed using intravascular OCT-NIRF imaging. This novel theranostic approach provides a promising theranostic strategy for high-risk coronary plaques.

Percutaneous Coronary Intervention for Chronic Total Occlusion in Single Coronary Arteries.

We retrospectively compared the results of percutaneous coronary intervention (PCI) and optimal medical therapy (OMT) for chronic total occlusion (CTO) in single coronary arteries to determine whether outcomes depend on the artery involved. From January 2004 through November 2015, a total of 731 patients were treated at our center for CTO in the left anterior descending coronary artery (LAD) (234 patients, 32%), left circumflex coronary artery (LCx) (184, 25.2%), or right coronary artery (RCA) (313, 42.8%). We further classified patients by treatment (PCI or OMT) and compared the cumulative incidence of major adverse cardiac events (MACE) and the composite of total death or myocardial infarction, as well as change in left ventricular ejection fraction from baseline. The 5-year cumulative incidence of MACE was similar between the treatment groups regardless of target vessel. The 5-year cumulative incidence of the composite of total death or myocardial infarction was significantly lower after PCI than after OMT or failed PCI in the LCx (2.6% vs 11.5%; P=0.020; log-rank) and RCA (5.8% vs 17.2%; P=0.002) groups, but not in the LAD group. Cox proportional hazards regression analysis indicated that PCI independently predicted a lower incidence of the composite of total death or myocardial infarction in the LCx group (hazard ratio [HR]=0.184; 95% CI, 0.0035-0.972; P=0.046) and the RCA group (HR=0.316; 95% CI, 0.119-0.839; P=0.021). The artery involved does not appear to affect clinical outcomes of successful PCI for single-vessel CTO. Further investigation in a randomized clinical trial is warranted.

New onset diabetes mellitus and cardiovascular events in Korean patients with acute myocardial infarction receiving high-intensity statins.

BACKGROUND: High-intensity statin therapy is typically used in patients with acute myocardial infarction (AMI) for secondary prevention. However, there have been consistent concerns regarding its association with diabetes mellitus. We investigated the effect of high-intensity atorvastatin and rosuvastatin on new-onset diabetes mellitus (NODM) and cardiovascular outcomes over a 3-year follow-up period. METHODS: Data from the Korea Acute Myocardial Infarction Registry were collected from November 2011 to October 2015, and 13,104 patients with AMI were enrolled from major cardiovascular centers. Among them, 2221 patients without diabetes who had been administered with high-intensity atorvastatin (40-80 mg) and rosuvastatin (20 mg) were investigated. The atorvastatin and rosuvastatin groups were evaluated for the incidence of NODM and major adverse cardiac events (MACE) including death, myocardial infarction, and revascularization cases in the following 3 years. RESULTS: Baseline characteristics were comparable between the two groups. Event-free survival rate of NODM was not significantly different between the atorvastatin and rosuvastatin groups (92.5% vs. 90.8%, respectively; Log-rank P-value = 0.550). The event-free survival rate of MACE was also not significantly different between atorvastatin and rosuvastatin groups (89.0% vs. 89.6%, respectively; Log rank P-value = 0.662). Multivariate Cox analysis revealed that statin type was not a prognostic factor in the development of NODM and MACE. CONCLUSIONS: Administering high-intensity atorvastatin and rosuvastatin in patients with AMI produced comparable effects on NODM and clinical outcomes, suggesting their clinical equivalence in secondary prevention.

Age and sex dependent association of uric acid and incident hypertension.

BACKGROUND AND AIMS: A previous meta-analysis suggested that the relationship between hyperuricemia and hypertension may be stronger in younger individuals and women. We aimed to investigate the age and sex dependent association of uric acid (UA) and incident hypertension. METHODS AND RESULTS: We analyzed data from the Health Examinees Study, a community-based prospective cohort study conducted in Korea from 2004 to 2013. It included 29,088 non-hypertensive subjects aged 40-79 (age, 52.5 ± 7.8 years; men, 31.4%) who had serum UA measurement and participated in the follow-up survey. The risk factors of hypertension were assessed using Cox regression. Over a mean 3.8 years of follow-up, 1388 men (15.2%) and 1942 women (9.7%) were newly diagnosed with hypertension. Upon age- and sex-based stratification, the risk of hypertension was highest in hyperuricemic subjects aged 40-49 years (HR: women, 2.16; men, 1.30). Across the entire cohort, the risk of incident hypertension was higher in groups with higher serum UA levels, and highest in women aged 40-49 years (HR, 1.44; P < 0.001). On multivariable linear regression analysis, the higher the baseline serum UA level, the greater the increase in blood pressure during follow-up, and this effect was strongest in women aged 40-49 years (ß = 0.87 and P < 0.01 for systolic blood pressure). CONCLUSIONS: The relationship between uric acid and incident hypertension tended to be dependent on age and sex. Younger women are at highest risk of UA-related incident hypertension.