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Familial history of hypertension, myocardial infarction, and stroke was on the basis of whether a member of the respond- ent's family (parents and siblings) had ...
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Comparison of Risk Factors Associated With Hypertension Subtypes by Classification Tree Method in Tongshan County of Jiangsu Province, China Hailei Wu1, Jiqu Xu1, Lang Zhuo2, Lingcai Han3, Wei Bao1, Shuang Rong1, Ping Yao1, Chenjiang Ying1 and Liegang Liu1 Background There are only a very limited number of studies relating to risk factors for hypertension in rural populations in China. There are even fewer studies comparing various hypertension subtypes. Methods A cross-sectional investigation was carried out in a representative sample of 20,390 subjects drawn from among 1,180,000 adult residents of Tongshan County of Jiangsu Province, China. The impact of risk factors including demographic, socioeconomic, dietary, and behavioral, on three hypertension subtypes, namely, isolated systolic hypertension (ISH), isolated diastolic hypertension (IDH), and systolic–diastolic hypertension (SDH), was analyzed by applying statistical tests and a classification tree. Results ISH was the predominant untreated hypertension subtype (13.68 ± 0.24%) in the adults of Tongshan County, followed by SDH

In China, hypertension has been clearly identified as a primary risk factor for heart disease and stroke, which are second and third, respectively, in the list of the leading causes of death.1 There are three subtypes of hypertension: isolated systolic hypertension (ISH), isolated diastolic hypertension (IDH), and systolic–diastolic hypertension (SDH). All three are associated with significantly increased risk for cardiovascular disease in Chinese adults.2 A review of previous epidemiologic trials reveals that studies of risk factors for hypertension in varied populations are limited, and it remains uncertain whether the traditional socioeconomic or dietary factors increase the risk of developing hypertension.3 Ultimately, a better understanding of the risk 1Department of Nutrition and Food Hygiene, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2Department of Epidemiology, School of Public Health, Xuzhou Medical College, Xuzhou, People’s Republic of China; 3Department of Epidemiology, Center for Disease Control and Prevention of Tongshan County, Xuzhou, People’s Republic of China. Correspondence: Liegang Liu ([email protected])

Received 29 April 2009; first decision 25 May 2009; accepted 24 August 2009; advance online publication 1 October 2009. doi:10.1038/ajh.2009.189 © 2009 American Journal of Hypertension, Ltd.

(11.70 ± 0.23%) and IDH (6.24 ± 0.17%). Age, number of cigarettes smoked daily, and the types of vitamins taken varied among the ISH, IDH, and SDH classification trees. Low socioeconomic status was associated with an increased risk for ISH and SDH. Light alcohol intake was associated with higher risk for ISH, but with lower risks for IDH and SDH. Light cigarette smoking was associated with higher ISH risk but lower SDH risk. The intake of appropriate amounts of fish, shrimp, or meat lowered the risks for ISH and IDH. The intake of appropriate amounts of seafood, eggs, milk, or fruit lowered the risks for all hypertension subtypes. Interestingly, an excessive preference for sweet or salty foods was associated with a higher risk for all the subtypes. Conclusions In Tongshan County, there was a considerable prevalence of hypertension of various subtypes, each associated with distinctive and complex risk factors. This suggests that there is a need for testing more diverse prevention measures, tailored to specific subtypes. Am J Hypertens 2009; 22:1287-1294 © 2009 American Journal of Hypertension, Ltd.

factors relating to hypertension may assist in devising direct strategies to prevent hypertension, thereby indirectly reducing the risk for stroke.4 However, few studies have made a though comparison of the various risk factors associated with the ­different subtypes of hypertension. In this study, we examined the prevalence of the various subtypes of hypertension in the adult population of Tongshan County, a rural area of China. We also compared the risk factors associated with ISH, IDH, and SDH, using statistical tests and classification trees. Applying the classification tree to specific situations provides a different approach to the design and management of future health intervention plans, once community-based studies have been carried out.5 Our study confirms that each subtype of hypertension is associated with distinctive risk factors and a corresponding pathogenesis. Methods

Study population. Tongshan County is located in the north of Jiangsu Province, China. The county has 1,180,000 residents, and its economic status is rated as mid-level, with limited medical resources. The target population of the study included individuals who were of ages 35 years and older and had

AMERICAN JOURNAL OF HYPERTENSION | VOLUME 22 NUMBER 12 | 1287-1294 | december 2009

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articles lived in the county for >5 years. These were assumed to be a ­representative sample of Chinese adult populations in many rural areas. The survey, conducted in March 2000, employed a stratified multistage probability sampling design, with the subjects being selected from sampling units predicated on geographical area and age, as determined by household registries. A total of 20,390 subjects were enrolled for physical examination, after obtaining their consent and after administering standardized questionnaires to them. Ultimately, information sought through the questionnaires was available for 20,364 individuals, the response rate of the survey being 99.87%. Data collection. Nurses were trained to take anthropometric measurements, record blood pressure (BP), and manage matters relating to the questionnaire. The questionnaire asked for details of demographic data, socioeconomic information, and dietary and behavioral information. Demographic data included age, gender, and familial history of hypertension, myocardial infarction, and stroke. Familial history of hypertension, myocardial infarction, and stroke was on the basis of whether a member of the respondent’s family (parents and siblings) had been diagnosed by a physician for any of those conditions. Socioeconomic information included education, marital status, family income, and access to medical resources. Behavioral and dietary information included alcohol intake, physical activities, food taste preferences, cigarette smoking, basal metabolic index, and frequency of intake of various kinds of foods. The weight of staple foods consumed daily was adjusted in terms of total caloric intake. An excessive level of consumption was defined as intake greater than the regular daily intake more often than three times a week. The appropriate level was defined as an intake greater than the regular daily intake one to three times a week. Heavy smoking was defined as the smoking of >10 cigarettes a day, while light smoking was defined as the smoking of 1–10 cigarettes a day. Heavy alcohol intake was defined as the intake of >25 ml of alcohol at a time more than two times a week, while light alcohol intake was defined as this level of intake one to two times a week. These data were obtained from self-reports of the participants. BP measurements were obtained on the right arm, with the participant in a seated posture with feet on the floor and arm supported at heart level, after at least 15 min of rest. An appropriate size of cuff and a standard mercury sphygmomano­ meter were used. Two readings each of systolic BP (SBP) and diastolic BP (DBP) were recorded within a 5-min interval, and averaged for data analysis. Participants were advised to refrain from consuming coffee, tea, or alcohol, smoking cigarettes, or indulging in vigorous exercise for at least 30 min before the BP readings. All the sphygmomanometers were checked and calibrated before use. Body weight and height were measured with the participants clad in light clothing and without footwear. Body weight, to the nearest 50 g, was measured using a portable balance scale, and height was measured, to the nearest 0.5 cm, using a portable steel measuring device. The body mass index (BMI) was 1288

Risk Factors Comparing Among Hypertension Subtypes

calculated as the weight in kilograms divided by the height in meters squared (kg/m2). The waistline was measured to the nearest 0.1 cm using a nonstretchable measuring tape, from the narrowest point between the lower borders of the rib cage and the iliac crest. Hip circumference was measured to the nearest 0.1 cm along the horizontal line at the widest point of the hip across the fullest part of the buttocks and over the end of the thigh bone. Definitions of hypertension and subgroups of hypertension. Hypertension was defined as an SBP ≥140 mm Hg or a DBP ≥90 mm Hg; this definition is consistent with World Health Organization guidelines.6 Three subtypes were defined for individuals who were not receiving any antihypertensive treatment at the time of the study: SDH was defined as an average SBP ≥140 mm Hg and an average DBP ≥90 mm Hg; IDH was defined as an average SBP 48.5

Vit C, Vit A, Mulvital

Node 4 Type % n Normotensives 88.89 696 ISH 11.11 87

Node 9 Type % n Normotensives 90.90 589 ISH 9.10 59 Total 3.99 648

n

Normotensives 74.73 414 ISH 25.27 140

Menstruation status, improvement = 0.001 Regularity Irregularity; menopause

Vit B

Total cigarette smoking dose, improvement = 0.001 >187,975 ≤187,975

Yes, no

Not sure Node 7

Type of vitamin intake, improvement = 0.014

Vit A, Vit B, Vit E, mulvital

Vit C Node 3 Type % Normotensives 90.19

30.60 4,970

Total

Type of vitamin intake, improvement = 0.004

4.54 738

24.11 3,916

Age, improvement = 0.002 >65.5

Node 25 Type % n Normotensives 76.82 1,402 ISH 23.18 423

Node 26 Type % n Normotensives 64.80 1,355 ISH 35.20 736

Total

Total

11.24 1,825

12.88 2,091

Figure 1 | The classification tree for ISH had 27 nodes. Age was the most important determining factor. The other split independent variables included the types of vitamins ingested, family history of stroke, total number of cigarettes smoked, type of tea consumed, menstruation status, waistline measurement, family history of hypertension, type of edible oil consumed, and body weight. ISH, isolated systolic hypertension.

control and better access and adherence to medical treatment in those belonging to higher socioeconomic status groups, and the greater incidence of low birth weights and job stresses in those of lower socioeconomic status groups.16 This study also indicated that the intake of appropriate amounts of fish, shrimp, or meat lowered the prevalence of ISH and IDH; the intake of appropriate amounts of seafood, eggs, milk, or fruit lowered the prevalence of ISH, IDH, and SDH; and a strong preference for excessively sweet or salty foods was associated with an increased prevalence of ISH, IDH, and SDH. We 1292

believe that good dietary habits are beneficial for the prevention and control of hypertension, and that sound populationwide approaches toward nutrition education are required in order to achieve this goal.17 Among the other factors, light intake of alcohol increased the risk for ISH but lowered the risk for IDH and SDH, which is a finding consistent with that from a previous study.18 Light cigarette smoking increased the risk for ISH while lowering the risk for SDH. The pathogenesis of hypertension is complex, and recent guidelines have focused on addressing total cardiovascular december 2009 | VOLUME 22 NUMBER 12 | AMERICAN JOURNAL OF HYPERTENSION

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Risk Factors Comparing Among Hypertension Subtypes

Node 0 Type % n Normotensives 91.63 13,533 IDH 8.37 1,236 Total ≤0.5 Node 1 Type % Normotensives 68.47 IDH 31.53 Total

100.00 14,769

Daily cigarette smoking dose, improvement = 0.002

>0.5 Node 2 Type % n Normotensives 91.81 13,457 IDH 8.19 1,201

n 76 35

0.75 111

Total

99.25 14,658

Type of vitamin intake, improvement = 0.002

Vit B Node 3 Type

Node 4 %

n

Type

Normotensives 90.73 137 IDH 9.27 14 Total

Type

Node 5

1.02 151

%

Node 6

Type

n

Total

%

Normotensives 93.94 62 IDH 6.06 4

Total

Total

Type

Node 9

Type

Node 13

%

n

Type

%

n

Type

%

n

92.17 13,612

Type

58.01 8,567

Node 14

%

n

Type

Node 10

%

Total

%

%

n

n

Type

6.06 895

Waistline, improvement = 0.001 >79.625

Node 11

%

n

Type

Node 12

%

n

Normotensives 88.92 4,486 IDH 11.08 559

Normotensives 88.17 IDH 11.83

395 53

Normotensives 72.93 IDH 27.07

326 121

Total

Total

448

Total

447

34.16 5,045

3.03

Type of drinking water, improvement = 0.002 Tap water Well water; pond water Node 15

Node 8

Normotensives 80.56 821 IDH 19.44 174

Frequency of eating seafood, improvement = 0.001 ≤79.625 Never; excessive

Type of tea, improvement = 0.002 Black tea; scented tea; green tea

Others

Node 7

Total

0.45 66

Normotensives 94.70 8,113 IDH 5.30 454 Total

98.22 14,507

Normotensives 92.56 12,599 IDH 7.44 1,013

Appropriate

Type

n

Family history of tumor, improvement = 0.002 Yes; not sure

No

n

Normotensives 88.24 75 IDH 11.76 10 0.58 85

%

Normotensives 91.82 13,320 IDH 8.18 1,187

Total alcohol intake, improvement = 0.001 >17,160

≤17,160

Vit C, Vit A, Vit E, Mulvital

n

Type

Node 16

%

n

3.03

Type of family cooking fuel, improvement = 0.001 Liquefied gas; straw Coal Type

Node 17

%

n

Type

Node 18

%

n

Normotensives 82.08 IDH 17.92

229 50

Normotensives 95.13 7,884 IDH 4.87 404

Normotensives 76.14 IDH 23.86

568 178

Normotensives 91.14 3,918 IDH 8.86 381

Normotensives 82.09 IDH 17.91

220 48

Normotensives 59.22 IDH 40.78

106 73

Total

279

Total

Total

746

Total

Total

268

Total

179

1.89

56.12 8,288

5.05

29.11 4,299

1.81

1.21

Figure 2 | The classification tree for IDH had 19 nodes. The number of cigarettes smoked per day was the most important determining factor. The other split independent variables included the types of vitamins ingested, total alcohol intake per week, family history of tumors, frequency of consumption of seafood, waistline measurement, type of tea consumed, type of drinking water consumed, and type of cooking fuel used in the home. IDH, isolated diastolic hypertension.

risk, recommending rational combinations of antihypertensive medication while also highlighting the importance of lifestyle interventions.19 The classification tree is considered to be the best of the currently available decision tree methods, because it is more likely to select the independent variable which is most different with respect to the target variable.20 In our study, the trees indicated different levels of risk factors for different hypertension subtypes. For ISH, age is probably the most important risk factor, the other risk factors being the types of vitamins ingested, family history of stroke, total number of cigarettes smoked, the type of tea consumed, menstruation status, waistline measurement, family history of hypertension, the type of edible oil consumed, and body weight. For IDH, daily cigarette smoking dose is probably the most important risk factor, followed by others such as the types of vitamins ingested, total alcohol intake per week, family history of tumor, frequency of consumption of seafood, waistline measurement, type of tea consumed, type of drinking water consumed, and type of cooking fuel used in the home. For SDH, the types of vitamins ingested could be the most important risk factor, the other risk factors being age, family history of tumors, frequency of consumption of seafood, body weight, BMI, total number of cigarettes AMERICAN JOURNAL OF HYPERTENSION | VOLUME 22 NUMBER 12 | december 2009

smoked, hip circumference, and frequency of alcohol intake per week. The intake of vitamins, especially vitamin D, might play different roles in different hypertension subtypes. Vitamin D receptors may be involved in the regulation of rennin expression, and vitamin D receptor polymorphisms have been shown to affect BP levels.21 Low vitamin D status is associated with an increased level of parathyroid hormone, which has been linked to hypertension.22 Our study confirmed that different hypertension subtypes have different pathogenesis and are associated with different extrinsic behavioral risk factors. Therefore the measures taken for prevention and management should be appropriate for the particular subtype. In summary, we investigated the prevalence of hypertension subtypes in adults of Tongshan County, and studied the relationships between hypertension subtypes and related risk factors. The classification trees of ISH, IDH, and SDH indicated that the related risk factors had different levels of impact on the different hypertension subtypes, and that the underlying mechanisms of action might be different. We believe these results and observations will be of benefit in preventing and controlling hypertension and cultivating a good lifestyle. We also believe that the use of powerful new techniques of 1293

articles

Risk Factors Comparing Among Hypertension Subtypes

n 13,533 2,316

Total

15,849

100.00

Type of vitamin intake, improvement = 0.039

Vit C; Vit A; Mulvital Node 1 %

Type

Node 0 Type % Normotensives 85.39 SDH 14.61

Vit B; Vit E

n

Normotensives 86.29 13,013 SDH 13.71 2,067 Total

95.15 15,080

>52.5

Node 3

Node 4

Type % Normotensives 92.45 SDH 7.55 Total

n 9,778 798

66.73 10,576

Family history of tumor, improvement = 0.002

Not sure

Yes, no

Total

Total

4.43 702

Type

Node 11 %

n

Normotensives 84.87 387 15.13 69 SDH Total

2.88 456

Type

Node 12 %

n

Normotensives 63.01 155 36.99 91 SDH 1.55 246

Total ≤174,287.5

Type

62.30 9,874

Type of vitamin intake, improvement = 0.002 Vit C Vit A; mulvital

Weight, improvement = 0.001 ≤63.75 >63.75

Type

Node 13 %

n

Node 14 %

Type

n

Normotensives 93.63 235 SDH 6.37 16

Total

Total

n

Type

Node 20 %

Type

1.58 251

Total cigarette smoking dose, improvement = 0.001 >174,287.5

Node 19 %

Node 5

Node 6

Type % Normotensives 71.83 SDH 28.17

n 3,235 1,269

Type % n Normotensives 70.90 324 SDH 29.10 133

Type % n Normotensives 62.82 196 SDH 37.18 116

Total

4,504

Total

Total

28.42

1.97 312

n

≤99.875

Type

Never; excessive Node 10 Type % n Normotensives 62.03 1,222 SDH 37.97 748

Total

Total

15.99 2,534

Node 15 %

n

Node 16 %

Type

n

Normotensives 81.41 1,962 SDH 18.59 448

Normotensives 41.13 58.87 SDH

51 73

Total

Total

0.78

124

15.21 2,410

Hip circumference, improvement = 0.001 >99.875

Node 21 %

n

Type

Node 22 %

≤6.5

n

Type

Node 23 %

Normotensives 84.06 1,772 SDH 15.94 336

Normotensives 62.91 190 SDH 37.09 112

Normotensives 67.34 SDH 32.66

Total

Total

798

Total

Total

Total

1.91 302

Type

10.95 1,735

Total

>25.981

Node 18 %

n

Normotensives 35.74 SDH 64.26

84 151

Total

235

1.48

Frequency of weekly alcohol intake, improvement = 0.002 >6.5

698 100

13.30 2,108

n

Normotensives 65.59 1,138 34.41 597 SDH

Normotensives 87.47 SDH 12.53 5.04

Node 17 %

Type

12.43 1,970

BMI, improvement = 0.002

≤25.981

Normotensives 94.08 8,303 SDH 5.92 522 55.68 8,825

2.88 457

Node 9 Type % n Normotensives 79.44 2,013 SDH 20.56 521

Family history of tumor, improvement = 0.002 Not sure

No

Normotensives 93.54 9,001 SDH 6.46 622 60.72 9,623

769

4.85

Appropriate

Normotensives 77.21 542 SDH 22.79 160

n

Total

Frequency of eating seafood, improvement = 0.004

Node 8 Type % n Normotensives 93.54 9,236 SDH 6.46 638

Type

Node 7 %

n 520 249

Type of vitamin intake, improvement = 0.010 Vit B Vit E

Age, improvement = 0.017 ≤52.5

Node 2 Type % Normotensives 67.62 SDH 32.38

n 973 472

9.12 1,445

Type

Node 24 %

n

Normotensives 56.90 165 SDH 43.10 125 Total

1.83 290

Figure 3 | The classification tree for SDH had 25 nodes. The types of vitamins ingested was the most important determining factor. The other split independent variables included age, family history of tumors, frequency of consumption of seafood, body weight, BMI, total number of cigarettes smoked, hip circumference, and frequency of alcohol intake per week. BMI, body mass index; SDH, systolic–diastolic hypertension.

genetics, genomics, and proteomics, integrated with systems physiology and population studies, will make it possible to find more selective and effective approaches to preventing hypertension subtypes in the coming decades. Acknowledgments: We are deeply indebted to all the subjects who were enrolled in this study, and to their relatives, for making this study possible. Disclosure: The authors declared no conflict of interest. 1. He J, Gu D, Wu X, Reynolds K, Duan X, Yao C, Wang J, Chen CS, Chen J, Wildman RP, Klag MJ, Whelton PK. Major causes of death among men and women in China. N Engl J Med 2005; 353:1124–1134. 2. Kelly TN, Gu D, Chen J, Huang JF, Chen JC, Duan X, Wu X, Yau CL, Whelton PK, He J. Hypertension subtype and risk of cardiovascular disease in Chinese adults. Circulation 2008; 118:1558–1566. 3. Akdag B, Fenkci S, Degirmencioglu S, Rota S, Sermez Y, Camdeviren H. Determination of risk factors for hypertension through the classification tree method. Adv Ther 2006; 23:885–892. 4. He J, Klag MJ, Wu Z, Whelton PK. Stroke in the People’s Republic of China. I. Geographic variations in incidence and risk factors. Stroke 1995; 26:2222–2227. 5. Teng JH, Lin KC, Ho BS. Application of classification tree and logistic regression for the management and health intervention plans in a community-based study. J Eval Clin Pract 2007; 13:741–748. 6. 1999 World Health Organization-International Society of Hypertension Guidelines for the Management of Hypertension. Guidelines subcommittee. J Hypertens 1999; 17:151–183. 7. Graham PL, Kuhnert PM, Cook DA, Mengersen K. Improving the quality of patient care using reliability measures: a classification tree approach. Stat Med 2007; 26:184–196. 8. Türe M, Kurt I, Kürüm T. Analysis of intervariable relationships between major risk factors in the development of coronary artery disease: a classification tree approach. Anadolu Kardiyol Derg 2007; 7:140–145. 9. Huang J, Wildman RP, Gu D, Muntner P, Su S, He J. Prevalence of isolated systolic and isolated diastolic hypertension subtypes in China. Am J Hypertens 2004; 17:955–962. 1294

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