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Treating Hypertension to Reduce Cardiovascular Risk: A Korean Perspective
Clinical Therapeutics/Volume 34, Number 7, 2012
Treating Hypertension to Reduce Cardiovascular Risk: A Korean Perspective Kwang-Il Kim, MD, PhD1,2; and Cheol-Ho Kim, MD, PhD1,2 1 2
Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea; and Seoul National University Bundang Hospital, Seongnam, Korea
ABSTRACT Background: Hypertension usually clusters with other cardiovascular risk factors; however, it has not been reported whether hypertension treatment has an impact on the awareness and treatment of other cardiovascular risk factors such as diabetes mellitus and hypercholesterolemia. Objective: To analyze the effect of hypertension treatment on the management of other risk factors in a Korean population. Methods: The Korean National Health and Nutrition Examination Survey (KNHANES) was a crosssectional, nationally representative survey in which a stratified multistage sampling design was used. The most recent KNHANES survey, conducted in 2008, was analyzed. Results: A total of 6547 adults (aged ⱖ20 years) were included in the analysis. Mean (SD) age was 49.1 (16.3) years, and 42.0% of the participants were male. The prevalence of hypertension, hypercholesterolemia, diabetes mellitus, and obesity was 26.9%, 10.5%, 9.5%, and 31.2%, respectively. The prevalence of diabetes mellitus, hypercholesterolemia, and obesity was significantly higher in the hypertensive group compared with normotensive participants (P ⬍ 0.001). Furthermore, clustering of cardiovascular risk factors was observed in the patients with hypertension. Treatment of hypertension was significantly associated with a higher awareness and treatment of diabetes mellitus and hypercholesterolemia, especially in moderate- to high-risk patients. Moreover, the total cholesterol concentration and glycosylated hemoglobin levels were significantly lower in the treated hypertensive patients (P ⬍ 0.001 for total cholesterol and P ⫽ 0.003 for glycosylated hemoglobin). Conclusions: Hypertension is a prevalent risk factor and is commonly associated with other cardiovascular risk factors. In the Korean population, treatment of hypertension can reduce global risk not
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only by lowering blood pressure but also by improving the control of other risk factors, such as diabetes mellitus and hypercholesterolemia. (Clin Ther. 2012;34:1559–1568) © 2012 Published by Elsevier HS Journals, Inc. Key words: awareness, hypercholesterolemia, hypertension, risk factor, treatment.
INTRODUCTION Hypertension rarely manifests alone but usually clusters with other cardiovascular risk factors, such as diabetes mellitus, obesity, and dyslipidemia. The clustering of risk factors independently increases the risk of developing cardiovascular disease, even in individuals with high-normal blood pressure.1 As a result, hypertensive patients with more cardiovascular risk factors are regarded as a high-risk group and show resistance to hypertension treatment.2 However, intensive multifactorial management of risk factors is highly effective in reducing global cardiovascular risk. Accordingly, global risk assessment and management have been highlighted as the most requested method to identify the high-risk group and to provide an optimal treatment plan for patients with hypertension. Recent treatment guidelines are now beginning to incorporate the concept of global cardiovascular risk evaluation and management to improve patient outcomes and are recommending global risk assessment in all patients with hypertension.3,4 However, it is not clear how often the strategy is executed in everyday practice. In addition, previous results have shown that the awareness and treatment of hypertension is significantly higher in patients with cardiovascular risk facAccepted for publication May 23, 2012. http://dx.doi.org/10.1016/j.clinthera.2012.05.006 0149-2918/$ - see front matter © 2012 Published by Elsevier HS Journals, Inc.
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Clinical Therapeutics tors.5,6 However, few articles have demonstrated the effect of hypertension treatment on the awareness and treatment of other cardiovascular risk factors, such as diabetes mellitus and hypercholesterolemia.7 Furthermore, it is unclear whether hypertension treatment has a different effect on the awareness and treatment of other risk factors according to the risk stratification. The importance of cardiovascular disease has been increasingly highlighted in Korea due to the rapid increase in the aging population and the shift to a westernized lifestyle in the younger generation. Accordingly, effective management of cardiovascular risk factors becomes an important issue in this country. Although the proportion of hypertensive patients who have their blood pressure controlled has increased over the past several decades, many Korean patients still do not reach an optimal level of blood pressure.8 Furthermore, the percentage of Korean patients in whom diabetes mellitus or dyslipidemia are controlled is also viewed as unsatisfactory.9,10 Thus, an optimal management strategy for the improvement of global cardiovascular risk control is needed. The aim of this study was to investigate the cardiovascular risk profile of Korean patients with hypertension and to analyze the effect of hypertension treatment on the management of other risk factors.
METHODS Study Population The data were derived from the second year (2008) of the Korean National Health and Nutrition Examination Survey (KNHANES) IV. The KNHANES has been conducted periodically since 1998 to assess the health and nutritional status of the noninstitutionalized, civilian population of Korea. The KNHANES IV was a cross-sectional and nationally representative survey conducted by the Division of Chronic Disease Surveillance, Korea Centers for Disease Control and Prevention from 2007 to 2009. The survey consists of a health interview survey, a nutrition survey, and a health examination survey. A stratified, multistage probability sampling design was used to select the household units. Briefly, 200 sampling frames from primary sampling units throughout Korea were selected randomly, and 23 households from each sampling frame (4600 households) were sampled by using a systemic sampling method. Among the 12,528 individuals chosen from these sampling frames, 9744 (77.8%) participated and completed the
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survey. More specific design and characteristics of the KNHANES are described elsewhere.11 Among the 9744 subjects who participated in the survey between February 2008 and December 2008, a total of 6547 patients (aged ⱖ20 years) were included in this analysis. This study was approved by the Institutional Research Committee of Seoul National University Bundang Hospital (Seongnam, Korea).
Measurement Blood pressure was measured with a mercury sphygmomanometer in accordance with the recommendation for blood pressure measurements.12 Three blood pressure readings were taken from the participants after 5 minutes of rest. The mean value of the second and third readings was calculated and recorded. A fasting blood sample was taken in the morning after at least 12 hours of fasting. The blood samples were centrifuged, refrigerated at the examination site, and then transferred in iceboxes to a central laboratory (NeoDin Medical Institute, Seoul, Korea) on the same day. Plasma glucose, total cholesterol, and triglyceride levels were measured by using an auto-analyzer (Hitachi Automatic Analyzer 7600, Hitachi, Tokyo, Japan). For patients with a history of diabetes or whose fasting plasma glucose met the criteria for diabetes in the examination, glycosylated hemoglobin was measured by using an HPLC assay (HLC-723G7, Tosoh Corporation, Tokyo, Japan). Body mass index (BMI) was calculated as the weight in kilograms divided by the height in meters squared. The waist circumference was measured from the narrowest point between the lower borders of the rib cage and the iliac crest.
Definition Hypertension was defined as blood pressure ⱖ140/90 mm Hg or current treatment with antihypertensive drugs. Hypercholesterolemia was defined as a total cholesterol level ⱖ240 mg/dL or current treatment with cholesterol-lowering agents. Diabetes mellitus was defined as a fasting glucose level ⱖ126 mg/dL or treatment with an oral agent or insulin.13 Obesity was defined as BMI ⱖ 25 kg/m2.14 Awareness of diabetes mellitus and hypercholesterolemia was defined by a “yes” response to the following items: “Has your health care provider ever told you that you have diabetes mellitus (or hypercholesterol-
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Table I. Comparison of clinical and laboratory characteristics between normotensive and hypertensive participants. Characteristic Age, mean (SD), y Male gender, no. (%) Current smoker, no. (%)† Family income, no. (%)‡ Lowest (⬍$520) Low–middle ($520–$1030) Middle–high ($1031–$1720) High (⬎$1720)
All (N ⫽ 6547)
Normotensive (n ⫽ 4784)
Hypertensive (n ⫽ 1763)
49.1 (16.3) 2751 (42.0) 1453 (22.3)
44.8 (15.1) 1971 (41.2) 1111 (23.4)
60.7 (13.4) 780 (44.2) 342 (19.5)
1313 (20.7) 1668 (26.3) 1661 (26.2) 1696 (26.8)
756 (16.3) 1207 (26.0) 1313 (28.2) 1372 (29.5)
557 (33.0) 461 (27.3) 348 (20.6) 324 (19.2)
Marital status Married Single/separate/divorced/widowed
4700 (71.8) 1847 (28.2)
3477 (72.7) 1307 (27.3)
1223 (69.4) 540 (30.6)
Education, no. (%) High school or more Less than high school
3939 (60.2) 2608 (39.8)
3319 (69.4) 1465 (30.6)
620 (35.2) 1143 (64.8)
Residential area, no. (%) Urban Rural
4813 (73.5) 1734 (26.5)
3656 (76.4) 1128 (23.6)
1157 (65.6) 606 (34.4)
Waist, mean (SD), cm BMI, mean (SD), kg/m2 WBC, mean (SD), ⫻103/L Hemoglobin, mean (SD), g/dL Glucose, mean (SD), mg/dL Cholesterol, mean (SD), mg/dL TG, median (IQR), mg/dL BUN, mean (SD), mg/dL Creatinine, mean (SD), mg/dL AST, mean (SD), IU/L ALT, mean (SD), IU/L
81.7 (9.8) 23.6 (3.3) 6.2 (1.7) 13.9 (1.5) 98.6 (25.2) 188.0 (36.1) 106.0 (71.0 – 162.0) 14.7 (4.6) 0.9 (0.3) 22.1 (14.9) 21.6 (19.5)
80.1 (9.5) 23.2 (3.2) 6.0 (1.7) 13.8 (1.6) 95.8 (21.7) 184.9 (34.6) 98.0 (67.0 – 147.0) 14.1 (4.2) 0.9 (0.2) 21.4 (14.4) 20.7 (20.1)
86.2 (9.4) 24.8 (3.3) 6.4 (1.9) 13.9 (1.5) 106.4 (31.5) 196.2 (38.9) 131.0 (89.0 – 199.0) 16.3 (5.2) 1.0 (0.4) 24.2 (15.9) 23.9 (17.4)
P* ⬍0.001 0.027 0.001 ⬍0.001
0.008
⬍0.001
⬍0.001
⬍0.001 ⬍0.001 ⬍0.001 0.040 ⬍0.001 ⬍0.001 ⬍0.001 ⬍0.001 ⬍0.001 ⬍0.001 ⬍0.001
BMI ⫽ body mass index; WBC ⫽ white blood cell count; TG ⫽ triglyceride; IQR ⫽ interquartile range; BUN ⫽ blood urea nitrogen; AST ⫽ aspartate aminotransferase; ALT ⫽ alanine aminotransferase. *P value for the comparison between normotensive and hypertensive participants. † Missing data for 37 patients. ‡ Missing data for 209 patients.
emia)?” or “Are any of the medications you take regularly for glucose (or cholesterol) control?” The participants were assigned to 3 different risk groups according to the revised National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP-III) guidelines: high risk (coronary heart disease [CHD], CHD risk equivalents), moderate risk (⬎2 risk factors), and low risk (0 –1 risk factor).15 CHD risk equivalents include no coronary forms of clinical atherosclerotic disease, diabetes mellitus, and multiple (ⱖ2) CHD risk factors with 10-year risk for CHD by
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using the Framingham scoring of ⬎20%. The major independent risk factors identified in the risk factor counting include cigarette smoking, hypertension, low HDL-C levels (⬍40 mg/dL), family history of premature CHD, and age (men, ⱖ45 years; women, ⱖ55 years). If a participant had a high HDL-C level (ⱖ60 mg/dL), 1 risk factor was subtracted from the count.
Statistical Analysis Statistical analyses were performed by using SPSS version 15.0 (SPSS Inc., Chicago, Illinois). Continu-
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Comparison Between Hypertensive and Normotensive Participants
Normotensive Hypertensive
Prevalence (%)
P < 0.001 50
46.9 P < 0.001
P < 0.001
19.2
18.8
25.4
25
7.5
5.9 0
DM
HC
Obesity
Figure 1. Prevalence of risk factors according to the presence of hypertension. Hypertension was associated with other cardiovascular risk factors, such as diabetes mellitus (DM), hypercholesterolemia (HC), and obesity.
ous variables are expressed as the mean (SD) or the median and interquartile range if the variables were not normally distributed. Continuous variables were compared by using either the unpaired Student t test or an analysis of variance followed by a post-hoc comparison with the Scheffé test. Discrete variables are expressed as counts and percentages, and the 2 or the Fisher exact test was used to compare proportions. Multivariate logistic regression analysis was performed to determine the independent effect of hypertension treatment on the awareness and treatment of diabetes mellitus and hypercholesterolemia, incorporating covariates for age, sex, BMI, family income, marital status, residential area, and education level. All statistical analyses were 2-tailed, and P values ⬍0.05 were considered to be statistically significant.
RESULTS Baseline Characteristics Baseline characteristics of the study population are presented in Table I. Mean age was 49.1 (16.3) years, and 42.0% of participants were male. The mean family income per month was 2.7 million won (⬃US $2500), and 71.8% lived with a spouse. The prevalence of hypertension, hypercholesterolemia, diabetes mellitus, and obesity was 26.9%, 10.5%, 9.5%, and 31.2%, respectively.
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Compared with normotensive participants, patients with hypertension were older, more likely to live alone, and had a lower level of education. The prevalence of diabetes mellitus, hypercholesterolemia, and obesity was significantly higher in patients with hypertension (Figure 1). The fasting glucose and total cholesterol concentrations were significantly higher in patients with hypertension (glucose, 95.8 [21.7] vs 106.4 [31.5] mg/dL; total cholesterol, 184.9 [34.6] vs 196.2 [38.9] mg/dL; P ⬍ 0.001, respectively) (Table I). In addition, patients with hypertension had more cardiovascular risk factors than the normotensive participants (Figure 2). Among the normotensive participants, 66.4% of them did not have any other cardiovascular risk factors. In contrast, 62.0% of the hypertensive patients had other cardiovascular risk factors.
No. of cardiovascular risk factors 0 1 2 3 4 Hypertensive P < 0.001 Normotensive
0
20
40 60 Percent (%)
80
100
Figure 2. Comparison of cardiovascular risk factor clustering in normotensive and hypertensive subjects. Compared with the normotensive participants, hypertensive patients were more likely to have other cardiovascular risk factors. The number of cardiovascular risk factors (range, 0 – 4) represents the sum of hypertension, diabetes mellitus, hypercholesterolemia, obesity, and current smoking. None of the study participants had all of the cardiovascular risk factors.
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Table II. Comparison of clinical and laboratory characteristics between nontreated and treated hypertensive patients. Characteristic Age, mean (SD), y Male sex, no. (%) Diabetes mellitus, no. (%) Hypercholesterolemia, no. (%) Obesity, no. (%) Current smoker, no. (%) SBP, mean (SD), mm Hg DBP, mean (SD), mm Hg Waist, mean (SD), cm BMI, mean (SD), kg/m2 WBC, mean (SD), ⫻103/L Hemoglobin, mean (SD), g/dL Glucose, mean (SD), mg/dL Cholesterol, mean (SD), mg/dL TG, median (IQR), mg/dL BUN, mean (SD), mg/dL Creatinine, mean (SD), mg/dL AST, mean (SD), IU/L ALT, mean (SD), IU/L
Nontreated Hypertensive (n ⫽ 642)
Treated Hypertensive (n ⫽ 1121)
P
54.4 (15.1) 362 (56.4) 65 (10.1) 95 (14.8) 291 (45.3) 177 (27.6) 141.7 (14.6) 90.9 (9.0) 85.1 (10.3) 24.7 (3.7) 6.5 (1.8) 14.4 (1.6) 102.6 (27.2) 201.3 (38.9) 135 (89–210) 15.1 (4.7) 0.9 (0.2) 25.2 (20.8) 26.2 (21.8)
64.3 (10.8) 418 (37.3) 273 (24.4) 236 (21.1) 536 (47.8) 165 (14.7) 129.3 (16.5) 78.6 (10.9) 86.9 (8.7) 24.9 (3.0) 6.4 (1.9) 13.7 (1.4) 108.5 (33.6) 193.3 (38.6) 130 (89–194) 17.0 (5.4) 1.0 (0.5) 23.7 (12.3) 22.6 (14.1)
⬍0.001 ⬍0.001 ⬍0.001 0.002 0.314 ⬍0.001 ⬍0.001 ⬍0.001 ⬍0.001 0.158 0.747 ⬍0.001 ⬍0.001 ⬍0.001 0.001 ⬍0.001 0.123 0.080 ⬍0.001
SBP ⫽ systolic blood pressure; DBP ⫽ diastolic blood pressure; BMI ⫽ body mass index; WBC ⫽ white blood cell; TG ⫽ triglyceride; IQR ⫽ interquartile range; BUN ⫽ blood urea nitrogen; AST ⫽ aspartate aminotransferase; ALT ⫽ alanine aminotransferase.
Effect of Hypertension Treatment on the Management of Other Cardiovascular Risk Factors The comparison between treated and nontreated hypertensive patients is presented in Table II. Diabetes mellitus and hypercholesterolemia were significantly more prevalent in the treated hypertensive patients; however, total cholesterol and triglyceride levels were significantly lower in the treated patients (P ⬍ 0.001 for cholesterol and P ⫽ 0.001 for triglycerides). The treatment of hypertension was associated with a better awareness and treatment of other risk factors, especially hypercholesterolemia (Figure 3). After adjusting for age, sex, and possible covariate affecting the awareness and treatment of diabetes mellitus and hypercholesterolemia, the association between hypertension treatment and higher awareness and treatment was maintained (Table III). Hypertension treatment
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was associated with a higher awareness of diabetes mellitus (adjusted odds ratio, 3.390 [95% CI, 1.801– 6.379]), but the association was much stronger with hypercholesterolemia (adjusted odds ratio, 13.515 [95% CI, 6.492–28.137]). Furthermore, a more significant association was found between hypertension treatment and hypercholesterolemia treatment (adjusted odds ratio, 20.610 [95% CI, 8.504 – 49.946]). Participants with both hypertension and hypercholesterolemia (n ⫽ 331) were categorized as low (n ⫽ 47), moderate (n ⫽ 164), or high (n ⫽ 120) risk (Table IV). The awareness of hypercholesterolemia was not significantly different according to the NCEP-ATP III risk group; however, treatment of hypercholesterolemia was significantly higher in the high-risk group (P ⫽ 0.038). The awareness and treatment of hypercholesterolemia were significantly higher in the
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100
P < 0.001
P = 0.005
P < 0.001
P < 0.001
82.8
Percent (%)
75
66.3
61.4 55.1
56.6 47.7
50
25
16.8 8.4
0 Awareness
Treatment
Awareness
Diabetes Mellitus
Treatment
Hypercholesterolemia Untreated HT
Treated HT
Figure 3. Awareness and treatment of diabetes mellitus and hypercholesterolemia according to treatment of hypertension (HT). The treatment of HT enhances the awareness and treatment of diabetes mellitus and hypercholesterolemia. In patients with HT and diabetes mellitus (n ⫽ 338), the awareness and treatment of diabetes mellitus was significantly higher in the treated hypertensive patients. Furthermore, the awareness and treatment of hypercholesterolemia were more dramatically increased in the treated hypertensive patients among the patients with HT and hypercholesterolemia (n ⫽ 331).
treated hypertensive patients, especially in the moderate- and high-risk groups (P ⬍ 0.001) (Figure 4). Furthermore, the serum total cholesterol concentration was significantly lower in the treated hyperten-
sive patients (252.3 [34.5] mg/dL in the nontreated hypertensive patients vs 218.6 [53.3] mg/dL in the treated hypertensive patients; P ⬍ 0.001). In patients with diabetes mellitus and hypertension (n ⫽ 338),
Table III. Logistic regression model of the effect of hypertension treatment on the awareness and treatment of diabetes mellitus and hypercholesterolemia. Age and Sex-Adjusted OR (95% CI) Risk Factor
Fully Adjusted OR* (95% CI)
Awareness
Treatment
Awareness
Treatment
Diabetes mellitus Nontreated hypertension Treated hypertension
1.0 3.336† (1.827–6.092)
1.0 1.912‡ (1.087–3.361)
1.0 3.390† (1.801–6.379)
1.0 1.879§ (1.051–3.357)
Hypercholesterolemia Nontreated hypertension Treated hypertension
1.0 13.874† (6.690–28.772)
1.0 21.086† (8.775–50.669)
1.0 13.515† (6.492–28.137)
1.0 20.610† (8.504–49.946)
OR ⫽ odds ratio. *Adjusted according to age, sex, body mass index, family income, marital status, residential area, and education level. † P ⬍ 0.001. ‡ P ⫽ 0.024. § P ⫽ 0.033.
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Table IV. Comparison of the different National Cholesterol Education Program Adult Treatment Panel III guidelines risk groups. Low Risk (n ⫽ 47)
Characteristics Age, mean (SD), y Male sex, no. (%) Current smoker, no. (%) Obesity, no. (%) Hypertension, no. (%) Awareness Treatment Hypercholesterolemia, no. (%) Awareness Treatment
Moderate Risk (n ⫽ 164)
High Risk (n ⫽ 120)
P
57.3 (12.3) 10 (21.3) 0 (0.0) 22 (46.8)
61.6 (12.5) 59 (36.0) 36 (22.0) 80 (48.8)
64.3 (9.8)* 34 (28.3) 14 (11.7) 69 (57.5)
0.002 0.113 ⬍0.0001 0.269
31 (66.0) 28 (59.6)
115 (70.1) 105 (64.0)
110 (91.7) 103 (85.8)
⬍0.0001 ⬍0.0001
23 (48.9) 18 (38.3)
74 (45.1) 59 (36.0)
64 (53.3) 61 (50.8)
0.392 0.038
*P ⬍ 0.05 compared with the low-risk group according to post-hoc analysis.
glycosylated hemoglobin was significantly lower in the treated hypertensive patients than in the nontreated hypertensive patients (7.3% [1.5%] vs 7.7%
Moderate risk
Low risk
100
P = 0.011
[1.9%]; P ⫽ 0.003). All of the data showed that treatment of hypertension might have a beneficial impact on the control of diabetes mellitus and hyper-
P = 0.001
P < 0.001
High risk
P < 0.001
P < 0.001
P < 0.001
75 Percent (%)
64.3
61.2
61
57.1
58.3
51.4 50 26.3 25
16.9 10.5
0
Awareness
Treatment
8.5 Awareness Untreated HT
Treatment
5.9 Awareness
5.9 Treatment
Treated HT
Figure 4. Effect of hypertension (HT) treatment on the awareness and treatment of hypercholesterolemia according to the National Cholesterol Education Program Adult Treatment Panel III (NCEP) risk stratification. Patients with HT and hypercholesterolemia (n ⫽ 331) were categorized according to the NCEP guideline as low (n ⫽ 47), moderate (n ⫽ 164), or high (n ⫽ 120) risk. The awareness and treatment of hypercholesterolemia were significantly higher in the treated hypertensive patients independent of the NCEP risk group.
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DISCUSSION Our findings indicate that hypertensive patients have more cardiovascular risk factors than normotensive subjects, and that treatment of hypertension has a beneficial effect on the awareness and treatment of other cardiovascular risk factors, especially hypercholesterolemia. Interestingly, the improvement in awareness and treatment of hypercholesterolemia associated with hypertension treatment was prominent in the moderate- and high-risk groups. Because the participants were a nationwide representation of the Korean population, we can conclude that Korean hypertensive patients are more likely to have a clustering of cardiovascular risk factors. Furthermore, strategies to improve hypertension treatment may be effective in reducing the global risk of cardiovascular events not only by improving blood pressure control but also by improving the control of other risk factors such as diabetes mellitus and hypercholesterolemia. Hypertension usually clusters with other cardiovascular risk factors, such as insulin resistance, visceral obesity, and dyslipidemia.16 The clustering of cardiovascular risk factors greatly increases an individual’s risk for cardiovascular morbidity and mortality.17 Intensive multifactorial treatment has been proven to be highly effective in reducing cardiovascular risk. Moreover, small reductions in an array of risk factors may be more beneficial than isolated large reductions in a single risk factor.18 Thus, risk factors and target organ damage must be actively screened for and treated if cardiovascular health is to be improved. Accordingly, international treatment guidelines have recognized the importance of having multiple cardiovascular risk factors and have included them in assessments of total cardiovascular risk and given recommendations on global therapeutic approaches to address all of the risk factors present in an individual.3,4 Hypertension is 1 of the most common chronic diseases and 1 of the most frequent reasons for clinic visits. Therefore, global risk assessment and management of hypertensive patients has to be taught to primary care physicians, and physicians should search for other risk factors and control them if indicated.19 However, it is not clear how often this strategy is executed in everyday practice.20 In addi-
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tion, there are few data on the interaction between the treatment of hypertension and the control of other cardiovascular risk factors. In the real world, despite the recognition that reducing blood pressure is essential to improving long-term cardiovascular health in hypertensive patients, only ⬍25% of hypertensive patients have adequate blood pressure control.21 Accordingly, efforts to improve the control rate of hypertension should be highlighted. However, it is not clear whether an improvement in hypertension control is associated with an improvement in the control of other cardiovascular risk factors such as diabetes mellitus and hypercholesterolemia. In this study, we observed that the cardiovascular risk factors cluster in the Korean population. Contrary to hypercholesterolemia and diabetes mellitus, which require blood tests to diagnose the disease, subjects can measure their own blood pressure, and thus elevated blood pressure is 1 of the most common reasons for clinic visits. Accordingly, it is practical to evaluate the global cardiovascular risk in a patient with hypertension receiving treatment. In other words, hypertension can be used as a gateway to begin total risk evaluation and management. In this study, we confirmed that hypertension was the most common cardiovascular risk factor, with a prevalence of ⬎25%. Although obesity is more common than hypertension, patients rarely visit clinics primarily for obesity. Accordingly, hypertensive patients are an appropriate target population for health care providers to focus on to evaluate cardiovascular risk. The treatment of hypertension was significantly associated with a better awareness and treatment of diabetes mellitus and hypercholesterolemia. In addition, the total cholesterol concentration and glycosylated hemoglobin levels were significantly lower in the treated hypertensive patients. Accordingly, hypertension treatment may improve the control of diabetes mellitus and hypercholesterolemia, which are related to global risk reduction. Furthermore, the treatment of hypertension and hypercholesterolemia was significantly higher in the high-risk group, which suggests that global risk evaluation and management were in fact executed in everyday practice.
CONCLUSIONS Hypertension treatment is associated with a better awareness and treatment of other cardiovascular risk factors because hypertension treatment and the subsequent
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K.-I. Kim et al. global risk evaluation permit the detection and treatment of the associated cardiovascular risk factors such as diabetes mellitus and hypercholesterolemia. In particular, hypertension is the most common cardiovascular risk factor and 1 of the most common reasons for clinic visits. Accordingly, we can expect an improvement in the control of cardiovascular risk factors with a hypertension management-driven reduction of the overall cardiovascular risk in a Korean population.
7.
8.
9.
ACKNOWLEDGMENT This study was supported by a research grant from Pfizer, Korea. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. Both authors contributed equally to the study design, data interpretation, and writing of the paper. As the corresponding author, Dr. C.H. Kim had full access to all the data in the study and was responsible for the decision to submit this manuscript for publication.
CONFLICTS OF INTEREST
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11.
12.
The authors have indicated that they have no conflicts of interest regarding the content of this article.
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type 1 diabetes population and a comparable general population. Diabetes Care. 2005;28:301–306. Wu Y, Tai ES, Heng D, et al. Risk factors associated with hypertension awareness, treatment, and control in a multiethnic Asian population. J Hypertens. 2009;27:190 –197. Kim KI, Kim Y, Kim HJ, et al. Current status and characteristics of hypertension treatment by primary physicians in Korea: data from Korean epidemiology study on hypertension (KEY study). Am J Hypertens. 2008;21:884 – 889. Lim S, Shin H, Song JH, et al. Increasing prevalence of metabolic syndrome in Korea: the Korean National Health and Nutrition Examination Survey for 1998 –2007. Diabetes Care. 2011;34:1323–1328. Choi YJ, Kim HC, Kim HM, et al. Prevalence and management of diabetes in Korean adults: Korea National Health and Nutrition Examination Surveys 1998 –2005. Diabetes Care. 2009;32:2016 –2020. Choi HS, Oh HJ, Choi H, et al. Vitamin D insufficiency in Korea—a greater threat to younger generation: the Korea National Health and Nutrition Examination Survey (KNHANES) 2008. J Clin Endocrinol Metab. 2011;96:643– 651. Pickering TG, Hall JE, Appel LJ, et al. Recommendations for blood pressure measurement in humans and experimental animals: Part 1: blood pressure measurement in humans: a statement for professionals from the Subcommittee of Professional and Public Education of the American Heart Association Council on High Blood Pressure Research. Hypertension. 2005;45:142–161. Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care. 1997;20: 1183–1197. World Health Organization Western Pacific Region. International Association for the Study of Obesity Task Force: the Asia-Pacific Perspective: Redefining Obesity and its Treatment. Sydney, Australia: Health Communications Australia; 2000: 15–21. Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation. 2002;106: 3143–3421. Petrella RJ, Merikle E. A retrospective analysis of the prevalence and treatment of hypertension and dyslipidemia in Southwestern Ontario, Canada. Clin Ther. 2008;30: 1145–1154. McAdam-Marx C, Bouchard J, Aagren M, et al. Concurrent control of blood glucose, body mass, and blood pressure in patients with type 2 diabetes: an analysis of data from electronic medical records. Clin Ther. 2011;33:110 –120. Ritz E. Total cardiovascular risk management. Am J Cardiol. 2007;100:53J– 60J.
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Address correspondence to: Cheol-Ho Kim, MD, PhD, Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Gumi-ro 166, Bundang-gu, Seongnam-si, Kyeongi-do, 463-707, Republic of Korea. E-mail: cheolkim@ snu.ac.kr
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Treating Hypertension to Reduce Cardiovascular Risk: A Korean Perspective Kwang-Il Kim, MD, PhD1,2; and Cheol-Ho Kim, MD, PhD1,2 1 2
Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea; and Seoul National University Bundang Hospital, Seongnam, Korea
ABSTRACT Background: Hypertension usually clusters with other cardiovascular risk factors; however, it has not been reported whether hypertension treatment has an impact on the awareness and treatment of other cardiovascular risk factors such as diabetes mellitus and hypercholesterolemia. Objective: To analyze the effect of hypertension treatment on the management of other risk factors in a Korean population. Methods: The Korean National Health and Nutrition Examination Survey (KNHANES) was a crosssectional, nationally representative survey in which a stratified multistage sampling design was used. The most recent KNHANES survey, conducted in 2008, was analyzed. Results: A total of 6547 adults (aged ⱖ20 years) were included in the analysis. Mean (SD) age was 49.1 (16.3) years, and 42.0% of the participants were male. The prevalence of hypertension, hypercholesterolemia, diabetes mellitus, and obesity was 26.9%, 10.5%, 9.5%, and 31.2%, respectively. The prevalence of diabetes mellitus, hypercholesterolemia, and obesity was significantly higher in the hypertensive group compared with normotensive participants (P ⬍ 0.001). Furthermore, clustering of cardiovascular risk factors was observed in the patients with hypertension. Treatment of hypertension was significantly associated with a higher awareness and treatment of diabetes mellitus and hypercholesterolemia, especially in moderate- to high-risk patients. Moreover, the total cholesterol concentration and glycosylated hemoglobin levels were significantly lower in the treated hypertensive patients (P ⬍ 0.001 for total cholesterol and P ⫽ 0.003 for glycosylated hemoglobin). Conclusions: Hypertension is a prevalent risk factor and is commonly associated with other cardiovascular risk factors. In the Korean population, treatment of hypertension can reduce global risk not
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only by lowering blood pressure but also by improving the control of other risk factors, such as diabetes mellitus and hypercholesterolemia. (Clin Ther. 2012;34:1559–1568) © 2012 Published by Elsevier HS Journals, Inc. Key words: awareness, hypercholesterolemia, hypertension, risk factor, treatment.
INTRODUCTION Hypertension rarely manifests alone but usually clusters with other cardiovascular risk factors, such as diabetes mellitus, obesity, and dyslipidemia. The clustering of risk factors independently increases the risk of developing cardiovascular disease, even in individuals with high-normal blood pressure.1 As a result, hypertensive patients with more cardiovascular risk factors are regarded as a high-risk group and show resistance to hypertension treatment.2 However, intensive multifactorial management of risk factors is highly effective in reducing global cardiovascular risk. Accordingly, global risk assessment and management have been highlighted as the most requested method to identify the high-risk group and to provide an optimal treatment plan for patients with hypertension. Recent treatment guidelines are now beginning to incorporate the concept of global cardiovascular risk evaluation and management to improve patient outcomes and are recommending global risk assessment in all patients with hypertension.3,4 However, it is not clear how often the strategy is executed in everyday practice. In addition, previous results have shown that the awareness and treatment of hypertension is significantly higher in patients with cardiovascular risk facAccepted for publication May 23, 2012. http://dx.doi.org/10.1016/j.clinthera.2012.05.006 0149-2918/$ - see front matter © 2012 Published by Elsevier HS Journals, Inc.
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Clinical Therapeutics tors.5,6 However, few articles have demonstrated the effect of hypertension treatment on the awareness and treatment of other cardiovascular risk factors, such as diabetes mellitus and hypercholesterolemia.7 Furthermore, it is unclear whether hypertension treatment has a different effect on the awareness and treatment of other risk factors according to the risk stratification. The importance of cardiovascular disease has been increasingly highlighted in Korea due to the rapid increase in the aging population and the shift to a westernized lifestyle in the younger generation. Accordingly, effective management of cardiovascular risk factors becomes an important issue in this country. Although the proportion of hypertensive patients who have their blood pressure controlled has increased over the past several decades, many Korean patients still do not reach an optimal level of blood pressure.8 Furthermore, the percentage of Korean patients in whom diabetes mellitus or dyslipidemia are controlled is also viewed as unsatisfactory.9,10 Thus, an optimal management strategy for the improvement of global cardiovascular risk control is needed. The aim of this study was to investigate the cardiovascular risk profile of Korean patients with hypertension and to analyze the effect of hypertension treatment on the management of other risk factors.
METHODS Study Population The data were derived from the second year (2008) of the Korean National Health and Nutrition Examination Survey (KNHANES) IV. The KNHANES has been conducted periodically since 1998 to assess the health and nutritional status of the noninstitutionalized, civilian population of Korea. The KNHANES IV was a cross-sectional and nationally representative survey conducted by the Division of Chronic Disease Surveillance, Korea Centers for Disease Control and Prevention from 2007 to 2009. The survey consists of a health interview survey, a nutrition survey, and a health examination survey. A stratified, multistage probability sampling design was used to select the household units. Briefly, 200 sampling frames from primary sampling units throughout Korea were selected randomly, and 23 households from each sampling frame (4600 households) were sampled by using a systemic sampling method. Among the 12,528 individuals chosen from these sampling frames, 9744 (77.8%) participated and completed the
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survey. More specific design and characteristics of the KNHANES are described elsewhere.11 Among the 9744 subjects who participated in the survey between February 2008 and December 2008, a total of 6547 patients (aged ⱖ20 years) were included in this analysis. This study was approved by the Institutional Research Committee of Seoul National University Bundang Hospital (Seongnam, Korea).
Measurement Blood pressure was measured with a mercury sphygmomanometer in accordance with the recommendation for blood pressure measurements.12 Three blood pressure readings were taken from the participants after 5 minutes of rest. The mean value of the second and third readings was calculated and recorded. A fasting blood sample was taken in the morning after at least 12 hours of fasting. The blood samples were centrifuged, refrigerated at the examination site, and then transferred in iceboxes to a central laboratory (NeoDin Medical Institute, Seoul, Korea) on the same day. Plasma glucose, total cholesterol, and triglyceride levels were measured by using an auto-analyzer (Hitachi Automatic Analyzer 7600, Hitachi, Tokyo, Japan). For patients with a history of diabetes or whose fasting plasma glucose met the criteria for diabetes in the examination, glycosylated hemoglobin was measured by using an HPLC assay (HLC-723G7, Tosoh Corporation, Tokyo, Japan). Body mass index (BMI) was calculated as the weight in kilograms divided by the height in meters squared. The waist circumference was measured from the narrowest point between the lower borders of the rib cage and the iliac crest.
Definition Hypertension was defined as blood pressure ⱖ140/90 mm Hg or current treatment with antihypertensive drugs. Hypercholesterolemia was defined as a total cholesterol level ⱖ240 mg/dL or current treatment with cholesterol-lowering agents. Diabetes mellitus was defined as a fasting glucose level ⱖ126 mg/dL or treatment with an oral agent or insulin.13 Obesity was defined as BMI ⱖ 25 kg/m2.14 Awareness of diabetes mellitus and hypercholesterolemia was defined by a “yes” response to the following items: “Has your health care provider ever told you that you have diabetes mellitus (or hypercholesterol-
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Table I. Comparison of clinical and laboratory characteristics between normotensive and hypertensive participants. Characteristic Age, mean (SD), y Male gender, no. (%) Current smoker, no. (%)† Family income, no. (%)‡ Lowest (⬍$520) Low–middle ($520–$1030) Middle–high ($1031–$1720) High (⬎$1720)
All (N ⫽ 6547)
Normotensive (n ⫽ 4784)
Hypertensive (n ⫽ 1763)
49.1 (16.3) 2751 (42.0) 1453 (22.3)
44.8 (15.1) 1971 (41.2) 1111 (23.4)
60.7 (13.4) 780 (44.2) 342 (19.5)
1313 (20.7) 1668 (26.3) 1661 (26.2) 1696 (26.8)
756 (16.3) 1207 (26.0) 1313 (28.2) 1372 (29.5)
557 (33.0) 461 (27.3) 348 (20.6) 324 (19.2)
Marital status Married Single/separate/divorced/widowed
4700 (71.8) 1847 (28.2)
3477 (72.7) 1307 (27.3)
1223 (69.4) 540 (30.6)
Education, no. (%) High school or more Less than high school
3939 (60.2) 2608 (39.8)
3319 (69.4) 1465 (30.6)
620 (35.2) 1143 (64.8)
Residential area, no. (%) Urban Rural
4813 (73.5) 1734 (26.5)
3656 (76.4) 1128 (23.6)
1157 (65.6) 606 (34.4)
Waist, mean (SD), cm BMI, mean (SD), kg/m2 WBC, mean (SD), ⫻103/L Hemoglobin, mean (SD), g/dL Glucose, mean (SD), mg/dL Cholesterol, mean (SD), mg/dL TG, median (IQR), mg/dL BUN, mean (SD), mg/dL Creatinine, mean (SD), mg/dL AST, mean (SD), IU/L ALT, mean (SD), IU/L
81.7 (9.8) 23.6 (3.3) 6.2 (1.7) 13.9 (1.5) 98.6 (25.2) 188.0 (36.1) 106.0 (71.0 – 162.0) 14.7 (4.6) 0.9 (0.3) 22.1 (14.9) 21.6 (19.5)
80.1 (9.5) 23.2 (3.2) 6.0 (1.7) 13.8 (1.6) 95.8 (21.7) 184.9 (34.6) 98.0 (67.0 – 147.0) 14.1 (4.2) 0.9 (0.2) 21.4 (14.4) 20.7 (20.1)
86.2 (9.4) 24.8 (3.3) 6.4 (1.9) 13.9 (1.5) 106.4 (31.5) 196.2 (38.9) 131.0 (89.0 – 199.0) 16.3 (5.2) 1.0 (0.4) 24.2 (15.9) 23.9 (17.4)
P* ⬍0.001 0.027 0.001 ⬍0.001
0.008
⬍0.001
⬍0.001
⬍0.001 ⬍0.001 ⬍0.001 0.040 ⬍0.001 ⬍0.001 ⬍0.001 ⬍0.001 ⬍0.001 ⬍0.001 ⬍0.001
BMI ⫽ body mass index; WBC ⫽ white blood cell count; TG ⫽ triglyceride; IQR ⫽ interquartile range; BUN ⫽ blood urea nitrogen; AST ⫽ aspartate aminotransferase; ALT ⫽ alanine aminotransferase. *P value for the comparison between normotensive and hypertensive participants. † Missing data for 37 patients. ‡ Missing data for 209 patients.
emia)?” or “Are any of the medications you take regularly for glucose (or cholesterol) control?” The participants were assigned to 3 different risk groups according to the revised National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP-III) guidelines: high risk (coronary heart disease [CHD], CHD risk equivalents), moderate risk (⬎2 risk factors), and low risk (0 –1 risk factor).15 CHD risk equivalents include no coronary forms of clinical atherosclerotic disease, diabetes mellitus, and multiple (ⱖ2) CHD risk factors with 10-year risk for CHD by
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using the Framingham scoring of ⬎20%. The major independent risk factors identified in the risk factor counting include cigarette smoking, hypertension, low HDL-C levels (⬍40 mg/dL), family history of premature CHD, and age (men, ⱖ45 years; women, ⱖ55 years). If a participant had a high HDL-C level (ⱖ60 mg/dL), 1 risk factor was subtracted from the count.
Statistical Analysis Statistical analyses were performed by using SPSS version 15.0 (SPSS Inc., Chicago, Illinois). Continu-
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Comparison Between Hypertensive and Normotensive Participants
Normotensive Hypertensive
Prevalence (%)
P < 0.001 50
46.9 P < 0.001
P < 0.001
19.2
18.8
25.4
25
7.5
5.9 0
DM
HC
Obesity
Figure 1. Prevalence of risk factors according to the presence of hypertension. Hypertension was associated with other cardiovascular risk factors, such as diabetes mellitus (DM), hypercholesterolemia (HC), and obesity.
ous variables are expressed as the mean (SD) or the median and interquartile range if the variables were not normally distributed. Continuous variables were compared by using either the unpaired Student t test or an analysis of variance followed by a post-hoc comparison with the Scheffé test. Discrete variables are expressed as counts and percentages, and the 2 or the Fisher exact test was used to compare proportions. Multivariate logistic regression analysis was performed to determine the independent effect of hypertension treatment on the awareness and treatment of diabetes mellitus and hypercholesterolemia, incorporating covariates for age, sex, BMI, family income, marital status, residential area, and education level. All statistical analyses were 2-tailed, and P values ⬍0.05 were considered to be statistically significant.
RESULTS Baseline Characteristics Baseline characteristics of the study population are presented in Table I. Mean age was 49.1 (16.3) years, and 42.0% of participants were male. The mean family income per month was 2.7 million won (⬃US $2500), and 71.8% lived with a spouse. The prevalence of hypertension, hypercholesterolemia, diabetes mellitus, and obesity was 26.9%, 10.5%, 9.5%, and 31.2%, respectively.
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Compared with normotensive participants, patients with hypertension were older, more likely to live alone, and had a lower level of education. The prevalence of diabetes mellitus, hypercholesterolemia, and obesity was significantly higher in patients with hypertension (Figure 1). The fasting glucose and total cholesterol concentrations were significantly higher in patients with hypertension (glucose, 95.8 [21.7] vs 106.4 [31.5] mg/dL; total cholesterol, 184.9 [34.6] vs 196.2 [38.9] mg/dL; P ⬍ 0.001, respectively) (Table I). In addition, patients with hypertension had more cardiovascular risk factors than the normotensive participants (Figure 2). Among the normotensive participants, 66.4% of them did not have any other cardiovascular risk factors. In contrast, 62.0% of the hypertensive patients had other cardiovascular risk factors.
No. of cardiovascular risk factors 0 1 2 3 4 Hypertensive P < 0.001 Normotensive
0
20
40 60 Percent (%)
80
100
Figure 2. Comparison of cardiovascular risk factor clustering in normotensive and hypertensive subjects. Compared with the normotensive participants, hypertensive patients were more likely to have other cardiovascular risk factors. The number of cardiovascular risk factors (range, 0 – 4) represents the sum of hypertension, diabetes mellitus, hypercholesterolemia, obesity, and current smoking. None of the study participants had all of the cardiovascular risk factors.
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Table II. Comparison of clinical and laboratory characteristics between nontreated and treated hypertensive patients. Characteristic Age, mean (SD), y Male sex, no. (%) Diabetes mellitus, no. (%) Hypercholesterolemia, no. (%) Obesity, no. (%) Current smoker, no. (%) SBP, mean (SD), mm Hg DBP, mean (SD), mm Hg Waist, mean (SD), cm BMI, mean (SD), kg/m2 WBC, mean (SD), ⫻103/L Hemoglobin, mean (SD), g/dL Glucose, mean (SD), mg/dL Cholesterol, mean (SD), mg/dL TG, median (IQR), mg/dL BUN, mean (SD), mg/dL Creatinine, mean (SD), mg/dL AST, mean (SD), IU/L ALT, mean (SD), IU/L
Nontreated Hypertensive (n ⫽ 642)
Treated Hypertensive (n ⫽ 1121)
P
54.4 (15.1) 362 (56.4) 65 (10.1) 95 (14.8) 291 (45.3) 177 (27.6) 141.7 (14.6) 90.9 (9.0) 85.1 (10.3) 24.7 (3.7) 6.5 (1.8) 14.4 (1.6) 102.6 (27.2) 201.3 (38.9) 135 (89–210) 15.1 (4.7) 0.9 (0.2) 25.2 (20.8) 26.2 (21.8)
64.3 (10.8) 418 (37.3) 273 (24.4) 236 (21.1) 536 (47.8) 165 (14.7) 129.3 (16.5) 78.6 (10.9) 86.9 (8.7) 24.9 (3.0) 6.4 (1.9) 13.7 (1.4) 108.5 (33.6) 193.3 (38.6) 130 (89–194) 17.0 (5.4) 1.0 (0.5) 23.7 (12.3) 22.6 (14.1)
⬍0.001 ⬍0.001 ⬍0.001 0.002 0.314 ⬍0.001 ⬍0.001 ⬍0.001 ⬍0.001 0.158 0.747 ⬍0.001 ⬍0.001 ⬍0.001 0.001 ⬍0.001 0.123 0.080 ⬍0.001
SBP ⫽ systolic blood pressure; DBP ⫽ diastolic blood pressure; BMI ⫽ body mass index; WBC ⫽ white blood cell; TG ⫽ triglyceride; IQR ⫽ interquartile range; BUN ⫽ blood urea nitrogen; AST ⫽ aspartate aminotransferase; ALT ⫽ alanine aminotransferase.
Effect of Hypertension Treatment on the Management of Other Cardiovascular Risk Factors The comparison between treated and nontreated hypertensive patients is presented in Table II. Diabetes mellitus and hypercholesterolemia were significantly more prevalent in the treated hypertensive patients; however, total cholesterol and triglyceride levels were significantly lower in the treated patients (P ⬍ 0.001 for cholesterol and P ⫽ 0.001 for triglycerides). The treatment of hypertension was associated with a better awareness and treatment of other risk factors, especially hypercholesterolemia (Figure 3). After adjusting for age, sex, and possible covariate affecting the awareness and treatment of diabetes mellitus and hypercholesterolemia, the association between hypertension treatment and higher awareness and treatment was maintained (Table III). Hypertension treatment
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was associated with a higher awareness of diabetes mellitus (adjusted odds ratio, 3.390 [95% CI, 1.801– 6.379]), but the association was much stronger with hypercholesterolemia (adjusted odds ratio, 13.515 [95% CI, 6.492–28.137]). Furthermore, a more significant association was found between hypertension treatment and hypercholesterolemia treatment (adjusted odds ratio, 20.610 [95% CI, 8.504 – 49.946]). Participants with both hypertension and hypercholesterolemia (n ⫽ 331) were categorized as low (n ⫽ 47), moderate (n ⫽ 164), or high (n ⫽ 120) risk (Table IV). The awareness of hypercholesterolemia was not significantly different according to the NCEP-ATP III risk group; however, treatment of hypercholesterolemia was significantly higher in the high-risk group (P ⫽ 0.038). The awareness and treatment of hypercholesterolemia were significantly higher in the
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100
P < 0.001
P = 0.005
P < 0.001
P < 0.001
82.8
Percent (%)
75
66.3
61.4 55.1
56.6 47.7
50
25
16.8 8.4
0 Awareness
Treatment
Awareness
Diabetes Mellitus
Treatment
Hypercholesterolemia Untreated HT
Treated HT
Figure 3. Awareness and treatment of diabetes mellitus and hypercholesterolemia according to treatment of hypertension (HT). The treatment of HT enhances the awareness and treatment of diabetes mellitus and hypercholesterolemia. In patients with HT and diabetes mellitus (n ⫽ 338), the awareness and treatment of diabetes mellitus was significantly higher in the treated hypertensive patients. Furthermore, the awareness and treatment of hypercholesterolemia were more dramatically increased in the treated hypertensive patients among the patients with HT and hypercholesterolemia (n ⫽ 331).
treated hypertensive patients, especially in the moderate- and high-risk groups (P ⬍ 0.001) (Figure 4). Furthermore, the serum total cholesterol concentration was significantly lower in the treated hyperten-
sive patients (252.3 [34.5] mg/dL in the nontreated hypertensive patients vs 218.6 [53.3] mg/dL in the treated hypertensive patients; P ⬍ 0.001). In patients with diabetes mellitus and hypertension (n ⫽ 338),
Table III. Logistic regression model of the effect of hypertension treatment on the awareness and treatment of diabetes mellitus and hypercholesterolemia. Age and Sex-Adjusted OR (95% CI) Risk Factor
Fully Adjusted OR* (95% CI)
Awareness
Treatment
Awareness
Treatment
Diabetes mellitus Nontreated hypertension Treated hypertension
1.0 3.336† (1.827–6.092)
1.0 1.912‡ (1.087–3.361)
1.0 3.390† (1.801–6.379)
1.0 1.879§ (1.051–3.357)
Hypercholesterolemia Nontreated hypertension Treated hypertension
1.0 13.874† (6.690–28.772)
1.0 21.086† (8.775–50.669)
1.0 13.515† (6.492–28.137)
1.0 20.610† (8.504–49.946)
OR ⫽ odds ratio. *Adjusted according to age, sex, body mass index, family income, marital status, residential area, and education level. † P ⬍ 0.001. ‡ P ⫽ 0.024. § P ⫽ 0.033.
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Table IV. Comparison of the different National Cholesterol Education Program Adult Treatment Panel III guidelines risk groups. Low Risk (n ⫽ 47)
Characteristics Age, mean (SD), y Male sex, no. (%) Current smoker, no. (%) Obesity, no. (%) Hypertension, no. (%) Awareness Treatment Hypercholesterolemia, no. (%) Awareness Treatment
Moderate Risk (n ⫽ 164)
High Risk (n ⫽ 120)
P
57.3 (12.3) 10 (21.3) 0 (0.0) 22 (46.8)
61.6 (12.5) 59 (36.0) 36 (22.0) 80 (48.8)
64.3 (9.8)* 34 (28.3) 14 (11.7) 69 (57.5)
0.002 0.113 ⬍0.0001 0.269
31 (66.0) 28 (59.6)
115 (70.1) 105 (64.0)
110 (91.7) 103 (85.8)
⬍0.0001 ⬍0.0001
23 (48.9) 18 (38.3)
74 (45.1) 59 (36.0)
64 (53.3) 61 (50.8)
0.392 0.038
*P ⬍ 0.05 compared with the low-risk group according to post-hoc analysis.
glycosylated hemoglobin was significantly lower in the treated hypertensive patients than in the nontreated hypertensive patients (7.3% [1.5%] vs 7.7%
Moderate risk
Low risk
100
P = 0.011
[1.9%]; P ⫽ 0.003). All of the data showed that treatment of hypertension might have a beneficial impact on the control of diabetes mellitus and hyper-
P = 0.001
P < 0.001
High risk
P < 0.001
P < 0.001
P < 0.001
75 Percent (%)
64.3
61.2
61
57.1
58.3
51.4 50 26.3 25
16.9 10.5
0
Awareness
Treatment
8.5 Awareness Untreated HT
Treatment
5.9 Awareness
5.9 Treatment
Treated HT
Figure 4. Effect of hypertension (HT) treatment on the awareness and treatment of hypercholesterolemia according to the National Cholesterol Education Program Adult Treatment Panel III (NCEP) risk stratification. Patients with HT and hypercholesterolemia (n ⫽ 331) were categorized according to the NCEP guideline as low (n ⫽ 47), moderate (n ⫽ 164), or high (n ⫽ 120) risk. The awareness and treatment of hypercholesterolemia were significantly higher in the treated hypertensive patients independent of the NCEP risk group.
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DISCUSSION Our findings indicate that hypertensive patients have more cardiovascular risk factors than normotensive subjects, and that treatment of hypertension has a beneficial effect on the awareness and treatment of other cardiovascular risk factors, especially hypercholesterolemia. Interestingly, the improvement in awareness and treatment of hypercholesterolemia associated with hypertension treatment was prominent in the moderate- and high-risk groups. Because the participants were a nationwide representation of the Korean population, we can conclude that Korean hypertensive patients are more likely to have a clustering of cardiovascular risk factors. Furthermore, strategies to improve hypertension treatment may be effective in reducing the global risk of cardiovascular events not only by improving blood pressure control but also by improving the control of other risk factors such as diabetes mellitus and hypercholesterolemia. Hypertension usually clusters with other cardiovascular risk factors, such as insulin resistance, visceral obesity, and dyslipidemia.16 The clustering of cardiovascular risk factors greatly increases an individual’s risk for cardiovascular morbidity and mortality.17 Intensive multifactorial treatment has been proven to be highly effective in reducing cardiovascular risk. Moreover, small reductions in an array of risk factors may be more beneficial than isolated large reductions in a single risk factor.18 Thus, risk factors and target organ damage must be actively screened for and treated if cardiovascular health is to be improved. Accordingly, international treatment guidelines have recognized the importance of having multiple cardiovascular risk factors and have included them in assessments of total cardiovascular risk and given recommendations on global therapeutic approaches to address all of the risk factors present in an individual.3,4 Hypertension is 1 of the most common chronic diseases and 1 of the most frequent reasons for clinic visits. Therefore, global risk assessment and management of hypertensive patients has to be taught to primary care physicians, and physicians should search for other risk factors and control them if indicated.19 However, it is not clear how often this strategy is executed in everyday practice.20 In addi-
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tion, there are few data on the interaction between the treatment of hypertension and the control of other cardiovascular risk factors. In the real world, despite the recognition that reducing blood pressure is essential to improving long-term cardiovascular health in hypertensive patients, only ⬍25% of hypertensive patients have adequate blood pressure control.21 Accordingly, efforts to improve the control rate of hypertension should be highlighted. However, it is not clear whether an improvement in hypertension control is associated with an improvement in the control of other cardiovascular risk factors such as diabetes mellitus and hypercholesterolemia. In this study, we observed that the cardiovascular risk factors cluster in the Korean population. Contrary to hypercholesterolemia and diabetes mellitus, which require blood tests to diagnose the disease, subjects can measure their own blood pressure, and thus elevated blood pressure is 1 of the most common reasons for clinic visits. Accordingly, it is practical to evaluate the global cardiovascular risk in a patient with hypertension receiving treatment. In other words, hypertension can be used as a gateway to begin total risk evaluation and management. In this study, we confirmed that hypertension was the most common cardiovascular risk factor, with a prevalence of ⬎25%. Although obesity is more common than hypertension, patients rarely visit clinics primarily for obesity. Accordingly, hypertensive patients are an appropriate target population for health care providers to focus on to evaluate cardiovascular risk. The treatment of hypertension was significantly associated with a better awareness and treatment of diabetes mellitus and hypercholesterolemia. In addition, the total cholesterol concentration and glycosylated hemoglobin levels were significantly lower in the treated hypertensive patients. Accordingly, hypertension treatment may improve the control of diabetes mellitus and hypercholesterolemia, which are related to global risk reduction. Furthermore, the treatment of hypertension and hypercholesterolemia was significantly higher in the high-risk group, which suggests that global risk evaluation and management were in fact executed in everyday practice.
CONCLUSIONS Hypertension treatment is associated with a better awareness and treatment of other cardiovascular risk factors because hypertension treatment and the subsequent
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K.-I. Kim et al. global risk evaluation permit the detection and treatment of the associated cardiovascular risk factors such as diabetes mellitus and hypercholesterolemia. In particular, hypertension is the most common cardiovascular risk factor and 1 of the most common reasons for clinic visits. Accordingly, we can expect an improvement in the control of cardiovascular risk factors with a hypertension management-driven reduction of the overall cardiovascular risk in a Korean population.
7.
8.
9.
ACKNOWLEDGMENT This study was supported by a research grant from Pfizer, Korea. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. Both authors contributed equally to the study design, data interpretation, and writing of the paper. As the corresponding author, Dr. C.H. Kim had full access to all the data in the study and was responsible for the decision to submit this manuscript for publication.
CONFLICTS OF INTEREST
10.
11.
12.
The authors have indicated that they have no conflicts of interest regarding the content of this article.
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Address correspondence to: Cheol-Ho Kim, MD, PhD, Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Gumi-ro 166, Bundang-gu, Seongnam-si, Kyeongi-do, 463-707, Republic of Korea. E-mail: cheolkim@ snu.ac.kr
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