Abstract
Hypertension is a leading risk factor for cardiovascular events and death. Despite differences in clinical implications of hypertension between men and women, guidelines establishing optimal blood pressure (BP) targets are still debated. The aim of this study was to investigate sex differences in the BP level associated with increased risks of major adverse cardiac and cerebral events (MACCEs) among antihypertensive‐treated patients. Using data from the Korean National Health Insurance Service‐National Sample Cohort, we enrolled antihypertensive‐treated patients and divided them into four categories: Group 1: SBP < 120 and DBP < 80 mm Hg; Group 2: 120 ≤ SBP < 130 and DBP < 80 mm Hg; Group 3: 130 ≤ SBP < 140 or 80 ≤ DBP < 90 mm Hg; and Group 4: SBP ≥ 140 or DBP ≥ 90 mm Hg. We performed time‐dependent cox regression analysis to investigate sex differences in the BP levels that increased the risk of MACCEs. Most of the 98 267 patients fell into Group 3 (53.2% men and 52.8% women) and Group 4 (30.5% men and 28.1% women). During 8.34 ± 2.07 years, there were 8,813 MACCEs and 791 deaths. The incidences of MACCEs and death tended to increase as the BP increased in both sexes. Compared to Group 1, the risk of MACCEs significantly increased only in Group 4 for men, while it significantly increased in Groups 3 and 4 for women. This study shows that there are sex differences in the BP level at which the risk of MACCEs increases. Our finding suggests that sex should be significantly considered when determining the optimal BP target in patients undergoing hypertension treatment.
Keywords: antihypertensive‐treated patients, blood pressure, hypertension, major cardiac and cerebral events, sex differences
1. INTRODUCTION
Hypertension is an important risk factor for cardiovascular disease (CVD) and death, and it has become a major global health burden with its high prevalence. 1 , 2 Thus, optimal blood pressure (BP) management among hypertensive patients is a primary strategy for preventing hypertension‐associated complications. 3 , 4 Although the benefits of lowering BP in reducing cardiovascular events (CVE) have been established through several clinical trials, 5 , 6 , 7 , 8 the optimal BP target in hypertensive patients has not been determined. Hypertension guidelines for BP management have been changed and updated several times based on the results of various randomized control trials and meta‐analyses. Some guidelines provided an individualized BP goal for specific subsets of hypertensive patients (eg, the elderly as well as those with diabetes, chronic kidney disease, and a history of cardiovascular diseases). 9 , 10 , 11 The latest guidelines provide detailed recommendations for BP management in hypertensive patients according to clinical conditions including age, race, degree of cardiovascular risk, and comorbidities. 12 , 13
Sex might be an important factor along with well‐established factors such as age or comorbidities when determining an optimal BP target. Several studies have revealed sex differences in the epidemiology and clinical characteristics of hypertension. 14 However, it is still unknown whether different optimal target BPs should be recommended for men and women.
Therefore, in this study, we investigated whether there are sex differences in the BP level associated with the risk of major adverse cardiac and cerebrovascular events (MACCEs) in antihypertensive‐treated patients is reduced.
2. MATERIALS AMD METHODS
2.1. Data source
This study was conducted using the Korean National Health Insurance Service‐National Sample Cohort (NHIS‐NSC) database, which is a population‐based cohort established by the NHIS. In South Korea, the NHIS provides periodic general health examinations to all insured individuals and their dependents. Except for non‐office workers, these individuals are required to undergo biennial health examinations and non‐office workers are required to undergo annual examinations. Among a target population of 46 605 433 individuals who underwent health examinations in 2002, a representative sample cohort of 1 025 340 participants was randomly selected (2.2% of the total eligible Korean population in 2002) and followed for 11 years (until 2013). The purpose of constructing the cohort was to provide public health researchers and policymakers with information regarding citizens’ utilization of health insurance and health examinations. The database contains patients’ sociodemographic information, their use of inpatient and outpatient services, pharmacy dispensing claims, and mortality data. The details of the NHIS‐NSC were described previously. 15 , 16
2.2. Study population
The NHIS‐NSC participants over 40 years old who received more than one health examination between 2003 and 2007 were evaluated (n = 475 494). Antihypertensive‐treated patients were defined as those who were prescribed antihypertensive medications for more than 30 days before a health examination (n = 122 142). We excluded patients who had hypotension (a BP less than 90/60 mm Hg) at least once during the study period or missing BP values (n = 4346). We also excluded patients who suffered a MACCE or chronic kidney disease before the first health examination date (index date) and patients who suffered a MACCE within one year after the index date (n = 19 529). After exclusions, 98 267 patients with hypertension were enrolled in this study (Figure 1). This study protocol was approved by the Institutional Review Board of Ewha Womans University, College of Medicine, and the requirement for informed consent was waived due to the retrospective nature of the study (EUMC 2018‐01‐039).
Figure 1.
Flow diagram. Index date: The day of the first health examination. Abbreviations; BP, blood pressure; CKD, chronic kidney disease; MACCE, major adverse cardiac and cerebral event
2.3. Data collection
Demographic and clinical data, which were recorded during health examinations, included age, sex, body mass index (BMI; calculated as weight/height2), and Charlson comorbidity index (CCI). 17 CCI was calculated using the method described by Sundararajan et al. 18 In this study, the 10th International Classification of Diseases (ICD‐10) code and weight for calculating CCI were used. Systolic BP (SBP) and diastolic BP (DBP) were measured three times by trained examiners, and the average of the second and third measurements was used in the analysis. 19 The following laboratory data were measured at health examinations: fasting blood glucose, total cholesterol, and proteinuria, which was measured by a dipstick test ([−], +, 1+, 2+, or over 3+).
2.4. Study outcomes and assessments
The primary endpoint for the study was the first occurrence of a MACCE as a composite outcome, which includes major adverse cardiac events (MACEs) and non‐fatal strokes. The secondary outcome was the incidence of a MACCE without death. MACE was composed of non‐traumatic all‐cause mortality, non‐fatal myocardial infarction (MI), and target vessel revascularization, including percutaneous coronary intervention and coronary artery bypass graft. Non‐fatal stroke included both ischemic stroke and hemorrhagic stroke. The occurrence of a MACCE was determined using medical claim data or medical history data. A MACCE was designated with the ICD‐10 codes: I20 (angina pectoris), I21 (acute MI), I22 (subsequent MI), I23 (certain current complications following acute MI), I63 (cerebral infarction), I60 (subarachnoid hemorrhage), I61 (intracerebral hemorrhage), or I62 (other non‐traumatic intracranial hemorrhage). In addition, a MACCE was considered to have occurred in patients who underwent angiography and required stent insertion, aortocoronary venous bypass graft angiography, percutaneous transluminal coronary angioplasty, percutaneous transcatheter placement of an intracoronary stent, percutaneous transluminal coronary atherectomy, cerebral or carotid percutaneous intravascular installation of a metallic stent, or aorta‐coronary vascular bypass surgery. 20 Data on death were confirmed by the National Population Registry of the Korea National Statistical Office with the use of a unique personal identification number. 21 All study participants were monitored for the occurrence of MACCEs until December 31, 2013.
2.5. Statistical analysis
Continuous variables were expressed as the mean ± standard deviation, and categorical variables were expressed as frequency and percentage. Similar to 2017 American College of Cardiology/American Heart Association guidelines, 12 the subjects were stratified into four categories based on baseline BPs: Group 1: SBP < 120 and DBP < 80 mm Hg (reference), Group 2: 120 ≤ SBP < 130 and DBP < 80 mm Hg, Group 3: 130 ≤ SBP < 140 or 80 ≤ DBP < 90 mm Hg, and Group 4: SBP ≥ 140 or DBP ≥ 90 mm Hg. Continuous variables were compared using analysis of variance, and categorical variables underwent chi‐square testing to compare the baseline characteristics among the groups. A time‐dependent Cox regression analysis was performed to evaluate whether sex affects the optimal target BP at which the risk of MACCEs is reduced when compared to Group 1; age, BMI, CCI, presence of diabetes mellitus, serum fasting blood glucose, total cholesterol levels, and presence of proteinuria were adjusted for multivariate analyses. The analysis was conducted using SAS (SAS Institute Inc. Cary, NC, USA) version 9.4, and P‐values less than 0.05 were considered statistically significant.
3. RESULTS
3.1. Baseline characteristics
The baseline characteristics of the 98 267 patients with hypertension are summarized in Table 1. The data for each sex are shown in Table S1 and Table S2. The subjects were stratified into four groups: Group 1 (10.6%, n = 10 392), Group 2 (7.0%, n = 6845), Group 3 (53.0%, n = 52 134), and Group 4 (29.4%, n = 28 896); most patients fell into Group 3. The mean age of the study patients was 59.1 ± 9.3 years (57.9 ± 9.3 in men and 60.5 ± 9.1 in women). Male patients accounted for 53.0% of total patients, and the proportion of male patients was slightly higher in Group 3 (53.1%) and Group 4 (55.0%) than that of female patients. Higher BP levels were associated with higher BMI, fasting glucose, and total cholesterol levels. In addition, the number of patients with proteinuria with a score greater than 2+ increased as the BP levels increased. Figure 2 shows the proportion of men and women in each BP group, and the distribution between men and women in each group seemed similar. Most patients fell into Group 3 (53.2% men and 52.8% women) and Group 4 (30.5% men and 28.1% women), while 9.8% of men and 11.4% of women fell into Group 1.
Table 1.
Baseline characteristics according to blood pressure groups
| Variables | Total (n = 98 267) | Group 1 (n = 10 392) | Group 2 (n = 6,845) | Group 3 (n = 52 134) | Group 4 (n = 28 896) | P value |
|---|---|---|---|---|---|---|
| Age (years) | 59.1 ± 9.3 | 58.6 ± 9.2 | 60.1 ± 9.2 | 59.2 ± 9.3 | 58.9 ± 9.3 | <0.001 |
| 40‐49 | 17055 (47.0) | 1925 (18.5) | 977 (14.3) | 8978 (17.2) | 5175 (17.9) | <0.001 |
| 50‐59 | 33163 (33.8) | 3677 (35.4) | 2246 (32.8) | 17405 (33.4) | 9835 (34.0) | |
| 60‐69 | 32426 (33.0) | 3264 (31.4) | 2371 (34.6) | 17226 (33.0) | 9565 (33.1) | |
| 70‐ | 15623 (15.9) | 1526 (14.7) | 1251 (18.3) | 8525 (16.4) | 4321 (15.0) | |
| Men, n (%) | 52056 (53.0) | 5108 (49.2) | 3383 (49.4) | 27673 (53.1) | 15892 (55.0) | <0.001 |
| BMI (kg/m2) | 25.1 ± 3.2 | 24.2 ± 3.0 | 24.6 ± 2.9 | 25.0 ± 3.0 | 25.2 ± 3.1 | <0.001 |
| <18.5 | 1250 (1.3) | 232 (2.2) | 100 (1.5) | 586 (1.1) | 332 (1.2) | <0.001 |
| 18.5‐25 | 50475 (51.4) | 6205 (59.8) | 3813 (55.7) | 26774 (51.4) | 13683 (47.4) | |
| 25‐30 | 41346 (42.1) | 3623 (34.9) | 2655 (38.8) | 22111 (42.4) | 12957 (44.9) | |
| 30≤ | 5147 (5.2) | 324 (3.1) | 276 (4.0) | 2644 (5.1) | 1903 (6.6) | |
| CCI | 0.88 ± 1.06 | 0.98 ± 1.13 | 0.97 ± 1.14 | 0.89 ± 1.07 | 0.79 ± 1.01 | <0.001 |
| Diabetes, n (%) | 19588 (19.9) | 2008 (19.3) | 1475 (21.6) | 10598 (20.3) | 5507 (19.1) | <0.001 |
| Fasting glucose (mg/dL) | 103.4 ± 33.9 | 100.9 ± 33.6 | 101.8 ± 29.3 | 103.2 ± 33.3 | 104.9 ± 36.0 | <0.001 |
| <100 | 56936 (58.0) | 6611 (63.7) | 4096 (59.9) | 30125 (57.8) | 16104 (55.8) | <0.001 |
| 100‐126 | 29495 (30.1) | 2730 (26.3) | 2018 (29.5) | 15876 (30.5) | 8871 (30.7) | |
| 126≤ | 11719 (11.9) | 1035 (10.0) | 725 (10.6) | 6078 (11.7) | 3881 (13.5) | |
| Total cholesterol (mg/dL) | 202.2 ± 38.2 | 196.4 ± 37.2 | 198.2 ± 37.4 | 202.1 ± 38.1 | 205.3 ± 38.7 | <0.001 |
| <200 | 48988 (50.0) | 5778 (55.7) | 3710 (54.3) | 26093 (50.1) | 13407 (46.5) | <0.001 |
| 200‐240 | 33957 (34.6) | 3356 (32.4) | 2207 (32.3) | 18013 (34.6) | 10381 (36.0) | |
| 240≤ | 15119 (15.4) | 1233 (11.9) | 910 (13.3) | 7932 (15.2) | 5044 (17.5) | |
| Proteinuria, n (%) | 1056 (1.1) | 84 (0.8) | 61 (0.9) | 512 (1.0) | 399 (1.4) | <0.001 |
| Follow‐up duration (year) | 8.34 ± 2.07 | 8.33 ± 1.91 | 8.43 ± 1.89 | 8.40 ± 2.03 | 8.09 ± 2.43 | <0.001 |
Abbreviations: BMI, body mass index; CCI, Charlson comorbidity index; DBP, diastolic blood pressure; SBP, systolic blood pressure.
Proteinuria was defined when a subject had a score of 2 + on random urinalysis.
Figure 2.
Proportion of blood pressure groups in male and female patients
3.2. Incidence of major adverse cardiac and cerebrovascular events according to BP groups
The mean duration of follow‐up was 8.34 ± 2.07 years. During the follow‐up period, 8813 cases of MACCEs and 791 deaths occurred among all patients (5140 cases and 561 deaths in men and 3673 cases and 230 deaths in women). The incidences of MACCEs and deaths tended to increase as BP increased irrespective of sex. Male patients showed a significantly higher incidence of MACCEs and deaths in all BP groups than female patients (Table 2).
Table 2.
Incidence of major adverse cardiac and cerebrovascular events according to blood pressure groups
| Total | Group 1 | Group 2 | Group 3 | Group 4 | |
|---|---|---|---|---|---|
| MACCE | |||||
| Male | |||||
| Persons | 5,140 | 619 | 457 | 2,800 | 1,264 |
| Person‐years | 426 548 | 65 865 | 47 259 | 247 310 | 66 113 |
| IR (95% CI) a | 12.1 (11.7‐12.4) | 9.4 (8.7‐10.1) | 9.7 (8.8‐10.6) | 11.3 (10.9‐11.7) | 19.1 (18.1‐20.2) |
| Female | |||||
| Persons | 3,673 | 370 | 305 | 2,024 | 974 |
| Person‐years | 393 074 | 59 444 | 46 200 | 224 662 | 62 768 |
| IR (95% CI) | 9.3 (9.0‐9.6) | 6.2 (5.6‐6.9) | 6.6 (5.9‐7.3) | 9.0 (8.6‐9.4) | 15.5 (14.5‐16.5) |
| MACCE without deaths | |||||
| Male | |||||
| Persons | 4,579 | 549 | 407 | 2,492 | 1,131 |
| Person‐years | 426 548 | 65 865 | 47 259 | 247 310 | 66 113 |
| IR (95% CI) | 10.7 (10.4‐11.0) | 8.3 (7.6‐9.0) | 8.6 (7.8‐9.4) | 10.1 (9.7‐10.5) | 17.1 (16.1‐18.1) |
| Female | |||||
| Persons | 3,443 | 341 | 281 | 1,902 | 919 |
| Person‐years | 393 074 | 59 444 | 46 200 | 224 662 | 62 768 |
| IR (95% CI) | 8.8 (8.5‐9.1) | 5.7 (5.1‐6.3) | 6.1 (5.4‐6.8) | 8.5 (8.1‐8.8) | 14.6 (13.7‐15.6) |
Abbreviations: CI, confidence interval; IR, incident rate; MACCE, major adverse cardiac cerebral event.
IR reported per 1000 person‐years.
3.3. Comparing the risk of MACCEs or MACCEs without death according to BP groups
Table 3 shows the time‐dependent, multivariate Cox regression analysis regarding the risk of primary and secondary outcomes according to BP groups. Using Group 1 as the reference, the risk of a MACCE (HR 1.819, 95% CI: 1.181‐2.802, P = 0.007) and a MACCE without death (HR 1.841, 95% CI: 1.164‐2.913, P = 0.009) significantly increased only in Group 4 after adjusting for age, sex, BMI, CCI, diabetes, fasting blood glucose level, total cholesterol level, and presence of proteinuria.
Table 3.
Multivariate Cox regression for major adverse cardiac and cerebrovascular events according to blood pressure groups
| HR | 95% CI | P value | ||
|---|---|---|---|---|
| MACCE | ||||
| SBP < 120 and DBP < 80 | Reference | |||
| 120 ≤ SBP<130 and DBP < 80 | 1.641 | 0.934 | 2.882 | 0.085 |
| 130 ≤ SBP<140 or 80 ≤ DBP90 | 1.269 | 0.836 | 1.927 | 0.263 |
| SBP ≥ 140 and DBP ≥ 90 | 1.819 | 1.181 | 2.802 | 0.007 |
| MACCE without death | ||||
| SBP < 120 and DBP < 80 | Reference | |||
| 120 ≤ SBP<130 and DBP < 80 | 1.526 | 0.829 | 2.808 | 0.175 |
| 130 ≤ SBP<140 or 80 ≤ DBP90 | 1.216 | 0.779 | 1.898 | 0.389 |
| SBP ≥ 140 and DBP ≥ 90 | 1.841 | 1.164 | 2.913 | 0.009 |
Abbreviations: CI, confidence interval; DBP, diastolic blood pressure; HR, hazard ratio; MACCE, major adverse cardiac and cerebral event; SBP, systolic blood pressure.
Adjusted for age, sex, body mass index, Charlson comorbidity index, diabetes mellitus, fasting blood glucose, total cholesterol, proteinuria
Next, we conducted subgroup analyses stratified by sex and age regarding the risk of MACCEs and MACCEs without death according to BP groups (Figure 3). First, there seemed to be different BP level which was associated with increased risk of MACCEs between male and female patients in each age group (Figure 3A). For patients in their 40s, the results indicated that the risk of MACCEs increased at SBP ≥ 120 mm Hg or DBP ≥ 80 mm Hg in female patients, while at SBP ≥ 140 mm Hg and DBP ≥ 90 mm Hg in male patients. For patients in their 50s, 60s, and 70s+, male showed similar results to patients in their 40s, whereas the risk of MACCEs in female significantly increased at SBP ≥ 130 mm Hg or DBP ≥ 80 mm Hg. In addition, for the occurrence of MACCEs without death, we observed similar results to those in Figure 3A,B. We conducted further subgroup analyses for diabetes (diabetes or non‐diabetes), proteinuria (proteinuria or non‐proteinuria), and total cholesterol level (<200 mg/dL, ≥200 mg/dL or < 240 mg/dL, ≥240 mg/dL). Subgroup analysis showed that there were sex differences in the BP level at which the risk of MACCEs increases in all subgroups. Except for female patients with the total cholesterol level ≥ 240 mg/dL and male patient with diabetes, the risk of MACCEs increased at SBP ≥ 130 mm Hg or DBP ≥ 80 mm Hg in female patients, while at SBP ≥ 140 mm Hg and DBP ≥ 90 mm Hg in male patients. Additional subgroup analyses also show that there is a sex‐specific correlation between achieved BP levels and the risk of MACCEs in antihypertensive‐treated patients (Table S3).
Figure 3.
Comparisons of risk of major adverse cardiac and cerebrovascular events between male and female patients. Abbreviations; BP, blood pressure; CI, confidential interval; DBP, diastolic blood pressure; HR, hazard ratio; MACCE, major adverse cardiac and cerebral event; SBP, systolic blood pressure. Adjusted for age, BMI, CCI, presence of diabetes mellitus, serum fasting blood glucose, total cholesterol levels, and presence of proteinuria
4. DISCUSSION
Using a Korean nationally representative cohort, we identified sex differences in the BP level associated with increased risk of MACCEs or MACCEs without death among antihypertensive‐treated patients. Moreover, this study implicated that the optimal BP target for reducing cardiovascular events may be lower in female patients compared to male patients.
Since the first report that showed men have consistently higher BPs than women, 22 the role of sex in hypertension has long been discussed. Prior studies have attributed sex to differences in epidemiology, clinical characteristics, treatment, and prognosis of hypertension. 23 , 24 , 25 , 26 , 27 The underlying mechanisms responsible for hypertension including the renin‐angiotensin system, sympathetic nervous system activity, sex hormones, endothelin‐1, and the immune system have also been shown to affect hypertension in men and women differently. 28 , 29 , 30 , 31 Ong et al. showed that there were sex differences in concomitant cardiovascular risk factors in hypertensive patients. 32 And there were differences in how elevated BP impacted cardiovascular complications between men and women. 33 . Based on the abundant evidence supporting sex‐specific differences in hypertension, guidelines for the management of hypertension may not be equally applicable to both men and women. However, no guidelines offer sex‐specific recommendations for optimal target BP. Even the latest European and American guidelines do not consider sex‐specific differences in hypertension management and suggest a BP target of < 130/80 mm Hg for both men and women. 12 , 13
A lack of data describing the effect of sex on the optimal target BPs for reducing the risk of adverse clinical outcomes is one of reasons why sex‐specific strategies for BP management are absent. The Systolic Blood Pressure Intervention Trial (SPRINT), which showed the beneficial effects of aggressive BP control, had also aimed to clarify optimal BP management in both men and women. 8 However, the number of cardiovascular events in female participants was lower than that seen in the general population, and the study was terminated early due to the benefits of more aggressive BP control among male participants. As a result, the differences in reaching outcomes were not statistically significance, and conclusions regarding the effect of intensive BP control could not be made in women. 34 , 35 The current study was conducted on hypertensive patients who took antihypertensive mediations longer than 30 days before health examination in order to establish the evidence that sex‐specific recommendations for optimal target BP are needed. This study showed that the risk of MACCEs significantly increased when BP was controlled at levels of SBP > 140 mm Hg or DBP > 90 mm Hg in total study patients. When we further analyzed these patients in subgroups stratified by age and sex, the risk of MACCEs significantly increased when BP was controlled at levels of SBP > 140 mm Hg or DBP > 90 mm Hg in male patients regardless of age. On the other hand, in female patients, the BP levels associated with increased risks of MACCEs were lower than those in male patients (SBP > 120 and DBP > 80 mm Hg for female patients in their 40s and SBP > 130 mm Hg or DBP > 80 mm Hg in all other age groups).
In our study, men and women under hypertension treatment showed a similar pattern of BP control status. When the most recently recommended target BP of < 130/80 mm Hg is applied, the proportion of hypertensive patients who reached the target BP was only 16.3% in men and 18.9% in women. Based on our results, BP control was worse in female patients than in male patients, and more female patients missed opportunities for the prevention of MACCE than male patients. Our results are supported by a study of 9357 subjects (4397 of which were women) that found women had a significantly higher risk of a CVE in relation to elevated BP when compared to men. 33 Hermida et al. also showed a dramatic correlation between higher ambulatory BP and the risk of a CVE in women than in men. 36 Although our results do not conclusively suggest an optimal sex‐specific BP target in hypertensive patients, we show that there are additional benefits from a more intensive BP‐lowering treatment in female patients, and the optimal target BP for hypertension treatment might be different between men and women.
There are several limitations to this study. First, the health examination sample cohort database included 10% of all participants who underwent health examinations provided by the NHIS between 2002 and 2003 and were followed until 2013. The participants were chosen by simple random sampling. Thus, these data do not represent the entire healthy Korean population. Moreover, this study was conducted with Korean adults only; therefore, caution must be taken in the interpretation of results due to ethnicity. Second, the study was a retrospective cohort observational study. Thus, selection bias could not be excluded completely. Future interventional prospective studies will be required to confirm these results. Third, since serial BP variations could not be measured individually, the current study's ability to show how BP should be managed is limited. Despite these limitations, this study is the first to investigate a correlation between achieved BP levels and clinical outcomes after age and sex stratification among antihypertensive‐treated patients in a large‐scale population‐based cohort.
5. CONCLUSIONS
In conclusion, this study shows that there is a sex‐specific correlation between achieved BP levels and the risk of MACCEs in antihypertensive‐treated patients. Therefore, sex should be considered when determining the optimal BP target in patients undergoing hypertension treatment.
CONFLICT OF INTEREST
None.
Supporting information
Tables S1‐S3
Acknowledgments
We are extremely grateful to all the participants who took part in this cohort. All authors are responsible for the critical review of the article and the decision to publish.
Kee YK, Kim M‐H, Oh HJ, Ryu D‐R. Sex differences in the blood pressure level associated with increased risks of cardiovascular events: a Korean nationwide population‐based cohort study. J Clin Hypertens. 2020;22:1638–1646. 10.1111/jch.13990
Funding information
This research was supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), which was funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI18C0844).
Contributor Information
Hyung Jung Oh, Email: ohjmd@naver.com.
Dong‐Ryeol Ryu, Email: drryu@ewha.ac.kr.
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Supplementary Materials
Tables S1‐S3