Obesity is the Most Important Determinant of Higher Blood Pressure Among Normotensive Chinese

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1 Chi nese Med i cal Jour nal (Taipei) 2002;65: Orig i nal Obesity is the Most Important Determinant of Higher Blood Pressure Among Normotensive Chinese Husan-Ming Tsao 1 Chen-Huan Chen 1,2,3 Kuan-Chia Lin 4 Pesus Chou 4 1 De part ment of Med i cine, Tai pei Vet erans Gen eral Hos pi tal; 2 De part ment of So cial Med i cine, 3 Car dio vas cu lar Re search Cen ter, and 4 Com mu nity Med i cine Re search Cen ter, Na tional Yang-Ming Uni ver sity, Tai pei, Tai wan, R.O.C. Key Words ep i de mi ol ogy; hy per ten sion; obe sity Background. Higher blood pres sure level in the normotensive range is a ma jor pre dic tor of the de vel op ment of hy per ten sion. The pur pose of the present study was to in ves ti gate the risk fac tor pro files among dif fer ent normotensive cat e go ries ac cord ing to the Sixth Re port of the Joint Na - tional Com mit tee on Pre ven tion, De tec tion, Eval u a tion and Treat ment of High Blood Pres sure (JNC VI). Methods. This com mu nity-based sur vey was con ducted in five coun ties of Kinmen from 1991 to We an a lyzed the data of fast ing blood sugar, in su lin, to tal and high-density li po pro tein cho les terol, triglyceride, blood urea ni tro gen, creatinine, body mass in dex (BMI), and waist cir cum fer - ence from 6,372 normotensive re spon dents (2511 men and 3861 women), who were cat e go rized into three groups (High Nor mal, Nor mal, and Op ti - mal) by JNC VI clas si fi ca tion. Re sults. By univariate anal y sis, sig nif i cant dif fer ences among the groups were shown in fast ing blood sugar, in su lin, triglyceride, to tal cho les terol, BMI and waist circumference in both male and female pop u la tion. By mul ti ple step wise lo gis tic re gres sion anal y sis, High Nor mal Group had sig nif i cantly higher per cent age of obe sity (OR = 2.96, 95% CI = in men; OR = 2.81, 95% CI = in women) than Optimal Group. Nor mal Group had more obe sity (OR = 2.01, 95% CI = in men; OR = 1.73, 95% CI = in women) than Op ti mal Group, and High Nor mal Group had more obe sity (OR = 1.81, 95% CI = in men; OR = 1.45, 95% CI = in women) than Nor mal Group. Con clu sions. Normotensive sub jects in the higher blood pres sure cat e go - ries had worse risk fac tor pro files. Obe sity was the most im por tant and con sis tent de ter mi nant of higher blood pres sure cat e go ries. [Chin Med J (Tai pei) 2002;65: ] Hy per ten sive heart dis ease is a ma jor con trib u tor to mor bid ity and mor tal ity in the Chi nese pop u - la tion. 1 It is well es tab lished that the car dio vas cu lar risk is di rectly re lated to the blood pres sure lev els. 2-6 How ever, the risk at trib ut able to high blood pres sure has not been com pletely elim i nated in spite of ef fec - tive re duc tion of blood pres sure. 7 There fore, the pre - ven tion of the de vel op ment of hy per ten sion in the normotensives would be the pre ferred strat egy to avoid the car dio vas cu lar risk Ac cord ing to the Sixth Re port of the Joint Na - tional Com mit tee on Pre ven tion, De tec tion, Eval u a - tion, and Treatment of High Blood Pres sure (JNC VI), 8 normotensive sub jects are fur ther cat e go rized Re ceived: August 22, Ac cepted: January 4, Cor re spon dence to: Chen-Huan Chen, MD, Division of Cardiology, Taipei Veterans General Hospital, 201, Sec. 2, Shih Pai Road, Taipei 112, Taiwan. Fax: ; chench@vghtpe.gov.tw

2 June 2002 Obe sity in Normotensives 269 into high-normal, nor mal, and op ti mal groups based on their blood pres sure lev els. Al though this new clas - sification for the normotensives re flects the con tin u - ous and graded re la tion ship be tween blood pres sure level and car dio vas cu lar risk, 9 dif fer ent normotensive range may carry dif fer ent car dio vas cu lar risk pro files that are im por tant for for mu lat ing pre ven tion strat egy. There fore, the pur pose of the pres ent study was to in - ves ti gate the risk fac tor pro files among dif fer ent normotensive cat e go ries ac cord ing to the JNC VI cri - te ria in a large Chi nese pop u la tion. Study population Methods Kinmen county of Tai wan has a pop u la tion of around 45,000 res i dents on one prin ci pal island (Quemoy) and sev eral nearby is lets; all are very close to the south ern Main land China. Dur ing the pe riod from 1991 to 1995, all res i dents over 30 years of age in five ma jor town ships (Kin-Hu, Kin-Chen, Kin-Sa, Kin-Nin, and Lieh-Yu) in Kinmen were sur veyed by the Yang-Ming Cru sade, a vol un teer or ga ni za tion of the med i cal stu dents from the Na tional Yang-Ming Uni ver sity. The overall re sponse rate was 62.5%, based on a tar get pop u la tion of by house hold reg is tra tion. The 6,372 (2511 men and 3861 women) normotensive sub jects (blood pres sure lev els be low 140/90 mmhg and never treated with antihypertensives) were used for cur rent in ves ti ga tion, which rep re sent 61% of all re spon dents from this sur vey. De mo graphic and clin i cal pa ram e ters in clud ing body height, body weight, waist cir cum fer ence and blood pres sures were doc u mented from door-to-door in ter views with struc tured ques tion naire. Af ter a more than 12 hours over night fast, se rum and plasma sam ples were col lected by venipuncture and kept frozen (-20 C) un til an a lyzed. Fasting plasma sugar was de ter mined by the hexokinase- glucose- 6-phophate dehydrogenase method with glu cose (HK) re agent kit (Gilford, Oberlin, Ohio). Fasting se rum in - su lin was de tected by radioim munoassay (Incstar Co., Stillwater, Oklahoma). Se rum cho les terol, triglyceride, uric acid, blood urea ni tro gen and creatinine were mea - sured by au to mated en zy matic meth ods with a Hitachi auto-analyzer (Hitachi Ltd, To kyo, Ja pan) and Boerhringer Mannheim Di ag nos tics re agents. Se rum high-density lipoprotein-cholesterol (HDL-C) was mea sured with a pre cip i ta tion method (Ko dak Ektachem HDL cho les terol kit). Se rum low-density li po pro tein was cal cu lated from the Friedewald equa tion. 10 Def i ni tion Sys tolic (SBP) and di a stolic (DBP) blood pres - sures were mea sured with three con sec u tive blood pres sure read ings, sep a rated by at least 5 min utes, taken from the right arm of seated sub jects. Di a stolic blood pres sure was mea sured at the fifth phase. Sub - jects with blood pres sure lev els be low 140/90 mmhg and never treated with antihypertensives were de fined as normotensives and were cat e go rized into highnormal (SBP or DBP mmhg: High Nor mal Group), nor mal (SBP < 130 and DBP < 85 mmhg: Nor mal Group), and op ti mal (SBP < 120 and DBP < 80 mmhg: Op ti mal Group) ac cord ing to the JNC VI clas si fi ca tion. 8 Sub jects were con sid ered to have type 2 di a be tes if they met the 1997 Amer i can Di a be tes As so ci a tion cri te ria. 11 Sub jects who gave a his tory of di a be tes un der treat ment with ei ther in su lin or oral antidiabetic agents were con sid ered to have known di a be tes re gard less of their plasma glu cose lev els. For sub jects with out a his tory of di a be tes, those with one fast ing plasma glu cose level of 126 mg/dl were con sid ered to have newly di ag nosed di a - be tes. Body mass in dex (BMI, weight/height 2 ) cor re - lates highly with ad i pos ity and has been rec om - mended as the mea sure of obe sity for adults. The Asians cut-offs for over weight ( 23 Kg/m 2 ) and obe - sity ( 25 kg/m 2 ) were adopted in this study. 12 Be cause waist cir cum fer ence may be the pre ferred mea sure of ab dom i nal obe sity, cen tral obe sity was there fore de - fined ac cord ing to the cut-offs of waist cir cum fer - ences > 90 cm in men or > 80 cm in women. 12 Ac cord - ing to the rec om men da tion of the Na tional Cho les - terol Ed u ca tion Pro gram, 13 the cri te ria for hy per cho - les ter ol emia were set as 240 mg/dl and for bor der - line hy per cho les ter ol emia, mg/dl. Sim i larly,

3 270 Husan-Ming Tsao, et al. Chi nese Med i cal Jour nal (Tai pei) Vol. 65 No. 6 Table 1. Baseline characteristicsamong high-normal, normal andoptimal bloodpressure Variables High Normal (n = 1028) Male Normal (n = 356) Optimal (n = 1127) P value High Normal (n = 1004) Female Normal (n = 353) Optimal (n = 2504) P value Age (y/o) < < Insulin(µU/mL) ± ± ± 5.86 < ± ± ± 6.21 < BMI (kg/m 2 ) ± ± ± 2.62 < ± ± ± 3.16 < Obesity(%) < < Waist circumference (cm) 84.8 ± ± ± 8.2 < ± ± ± 9.1 < Central Obesity (%) < < Triglyceride (mg/dl) ± ± ± < ± ± ± < Fastingplasma glucose (mg/dl) ± ± ± ± ± ± < Smoking(%) Alcohol intake (%) Cholesterol (mg/dl) ± ± ± ± ± ± < Uric acid (mg/dl) 6.31 ± ± ± ± ± ± HDL-C (mg/dl) ± ± ± ± ± ± Creatinine (mg/dl) 0.89 ± ± ± ± ± ± Blood urea nitrogen(mg/dl) ± ± ± ± ± ± BMI = body mass index; HDL-C = high density lipoprotein-cholesterol. the cri te ria for high tri glyc er ides were set as 200 mg/dl (in clud ing the very high tri glyc er ides cat e - gory) and for bor der line-high tri glyc er ides, mg/dl. 13 Cut-off val ues for el e vated plasma creatinine and blood urea ni tro gen were 1.3 mg/dl and 23 mg/dl re spec tively, us ing the 95 th per cen tile of gen - eral pop u la tion dis tri bu tion. Sta tis ti cal anal y sis Univariate anal y sis for the risk fac tors was done by Anal y sis of Vari ance (ANOVA) and Chi-square test. Mul ti ple step wise lo gis tic re gres sion strat i fied by sex was used to study the risk fac tors in the groups with dif fer ent lev els of blood pres sure. Sta tis ti cal sig - nif i cance was set at p < All sta tis tics were an a - lyzed us ing the Sta tis ti cal Anal y sis Sys tem (SAS) software. Result Univariate anal y sis (Ta ble 1) In males, age was pos i tively re lated to blood pres - sure (p < 0.001). The sig nif i cant dif fer ences among the High Nor mal, Nor mal, and Op ti mal Groups were shown in lev els of fast ing in su lin, fast ing plasma glu - cose, se rum triglyceride, to tal cho les terol, BMI, waist cir cum fer ence, and per cent ages of obe sity and cen tral obe sity. The three groups also dif fered with re spect to other health re lated fac tors, such as smok ing sta tus and al co hol con sump tion. In fe males, age was also pos i tively re lated to blood pres sure (p < 0.001). The dif fer ences among the High Nor mal, Nor mal, and Op ti mal Groups were shown in lev els of fast ing in su lin, fast ing plasma glu - cose, se rum triglyceride, to tal cho les terol, HDL-C, uric acid, blood urea ni tro gen, BMI, waist cir cum fer - ence, per cent ages of obesity, cen tral obesity, and smok ing sta tus. Mul ti ple lo gis tic regression anal y sis (Ta bles 2 and 3) In males, the prev a lence of obe sity was sig nif i - cantly dif fer ent among the three groups af ter ad just ing for var i ous pa ram e ters (High Nor mal Group vs. Nor - mal Group: OR = 1.81, 95% CI = ; Nor mal Group vs. Op ti mal Group: OR = 2.01, 95% CI = ; High Nor mal Group vs. Op ti mal Group: OR = 2.96, 95% CI = ). More obese sub jects were

4 June 2002 Obe sity in Normotensives 271 Table 2. Odds ratio (OR) and 95% confidence interval (95% CI) of risk factor profile for different normotensive groups of male residents aged 30 in Kinmen Separate comparison High Normal vs. Optimal Normal vs. Optimal High Normal vs. Normal Variables OR 95% CI OR 95% CI OR 95% CI Age (y/o) NS NS Diabetes (yes vs. no) NS NS NS NS NS NS Cholesterol 240 vs. < 200 (mg/dl) NS NS NS NS NS NS vs. < 200 (mg/dl) NS NS NS NS NS NS Overallobesity (yes vs. no) Central obesity (yes vs. no) NS NS NS NS NS NS Fasting insulin (µu/ml) NS NS Alcoholconsumption (yes vs. no) NS NS NS NS Smoking (yes vs. no) NS NS Triglyceride 200 vs. < 150 (mg/dl) NS NS NS NS NS NS 150~199 vs. < 150 (mg/dl) NS NS Creatinine NS NS NS NS NS NS HDL-C NS NS NS NS NS NS Uric acid NS NS NS NS NS NS Blood urea nitrogen NS NS NS NS NS NS NS = Non-significant; HDL-C= highdensity lipoprotein-cholesterol. Table 3. Odds ratio (OR) and 95% confidence interval (95% CI) of risk factor profiles in different normotensive groups of female residents aged 30 in Kinmen Separate comparison High Normal vs. Optimal Normal vs. Optimal High Normal vs. Normal Variables OR 95% CI OR 95% CI OR 95% CI Age (y/o) NS NS Diabetes (yes vs. no) NS NS NS NS NS NS Cholesterol 240 vs. < 200 (mg/dl) NS NS NS NS vs. < 200 (mg/dl) NS NS NS NS Overall obesity (yes vs. no) Central obesity (yes vs. no) NS NS NS NS NS NS Fasting insulin (µu/ml) NS NS Alcoholconsumption (yes vs. no) NS NS NS NS NS NS Smoking (yes vs. no) NS NS NS NS NS NS Triglyceride 200 vs. < 150 (mg/dl) NS NS NS NS NS NS vs. < 150 (mg/dl) NS NS NS NS NS NS Creatinine NS NS NS NS NS NS HDL-C NS NS NS NS NS NS Uric acid NS NS NS NS NS NS Blood urea nitrogen NS NS NS NS NS NS NS = Non-significant; HDL-C = high densitylipoprotein-cholesterol. found in the groups with higher blood pres sure. In con trast, the prev a lence of cen tral obe sity was not in - de pend ently as so ci ated with the blood pres sure. Other sig nif i cant in de pend ent pre dic tors for High Nor mal

5 272 Husan-Ming Tsao, et al. Chi nese Med i cal Jour nal (Tai pei) Vol. 65 No. 6 Group vs. Op ti mal Group in cluded age, fast ing in su lin lev els, al co hol con sump tion, smok ing, and bor der line high triglyceride lev els. For Nor mal Group vs. Op ti - mal Group, sig nif i cant in de pend ent pre dic tors also in - cluded age, fast ing in su lin lev els, smok ing, and bor - der line high triglyceride lev els. In fe males, the prev a lence of obe sity was also sig - nif i cantly dif fer ent among the blood pres sure groups af ter ad just ing for var i ous pa ram e ters (High Nor mal Group vs. Nor mal Group, OR = 1.45, 95% CI = ; Nor mal Group vs. Op ti mal Group: OR = 1.73, 95% CI = ; High Nor mal Group vs. Op ti mal Group: OR = 2.81, 95% CI = ). Sim i lar to male, the prev a lence of cen tral obe sity in fe males was not in de pend ently as so ci ated with the blood pres sure. Other sig nif i cant in de pend ent pre dic tors for High Nor mal Group vs. Op ti mal Group in cluded age, hy - per cho les ter ol emia and bor der line hy per cho les ter ol - emia, and fast ing in su lin lev els. For Nor mal Group vs. Op ti mal Group, sig nif i cant in de pend ent pre dic tors also in cluded age and fast ing in su lin level. Discussion Our re sults dem on strated dis tinct risk fac tor pro - files for the normotensive Chi nese cat e go rized by the JNC VI clas si fi ca tion. Obe sity is an in de pend ent discriminator be tween High Nor mal and Nor mal, and be tween Nor mal and Op ti mal blood pres sure cat e go - ries, for both men and women. These find ings sup port that obe sity is a ma jor con trol la ble con trib u tor to hy - pertension The as so ci a tion of body weight and BMI with blood pres sure has been in ves ti gated by sev eral stud - ies BMI at base line and weight gain on fol low-up are im por tant de ter mi nants of fu ture hy per ten sion. 21 In the Framingham Study, a 5% weight gain on fol - low-up was as so ci ated with 20-30% in creased odds of hy per ten sion in in di vid u als with out hy per ten sion. 21 Es ti ma tion sug gested that 78% of hy per ten sion in men and 65% in women could be di rectly at trib ut able to obe sity. 22 In over weight adults with high-normal blood pres sure, weight loss and re duced so dium in - take, in di vid u ally or in com bi na tion, are ef fec tive in low er ing sys tolic and di a stolic blood pres sure, thus to re duce hy per ten sion in ci dence. 5 Con trol of hy per ten sion ef fec tively re duces the mor bid ity and mor tal ity re lated to car dio vas cu lar dis - eases, but the ef fec tive ness is lim ited by the knowl - edge that antihypertensive med i ca tions re duce rather than elim i nate the risk, the drug-related ad verse ef - fect, and the high cost of some med i ca tions. 8,23 So the more rea son able ap proach should be the cor rec tion of the risk fac tors of high blood pres sure to pre vent blood pres sure from ris ing. 17 Among the risk fac tor pro files in Chi nese sub jects with High Nor mal, Nor - mal or Op ti mal blood pres sure, obe sity was the most con sis tent discriminator. There fore, weight con trol ap pears to be the ap proach of choice for the pre ven - tion of hy per ten sion. 5,21 Weight con trol has other ben - e fits be yond blood pres sure low er ing, in clud ing the im prove ment of dyslipidemia and glu cose in tol er - ance. 22,24 A se ries of en do crine, ge netic, met a bolic, and hemodynamic mech a nisms have been linked to the de vel op ment of hy per ten sion in the obese. 25 These in - clude in su lin re sis tance and/or hyperinsulinemia, over-activation of the sym pa thetic ner vous sys tem, the renin-angiotensin-aldosterone sys tem, salt re ten - tion, ge netic pre dis po si tion, leptin lev els, and thermogenesis Re duc tion of body weight may re - verse the hemodynamic ab nor mal i ties and lower the blood pres sure. 24,31 Our data also sug gested the clus ter ing of met a - bolic risk fac tors in the normotensives with higher blood pres sure lev els. Un fa vor able met a bolic pro files, such as hyperinsulinemia, hyperglycemia, hy per cho - les ter ol emia and hypertriglyceridemia, tended to be more fre quently noted in the groups with higher lev els of blood pres sure. Al though less ob vi ous than obe sity, the co ex is tence of met a bolic ab nor mal i ties and high blood pres sure lev els in the normotensive Chi nese was also ev i dent. The clus ter ing of the car dio vas cu lar risk fac tors in the normotensives may in di cate some role of in su lin re sis tance in the de vel op ment of hy per - ten sion in this pop u la tion. 32 How ever, in the normoglycemic Hong Kong Chi nese, obe sity ap pears to have a pre dom i nant role com pared with in su lin re - sis tance in de ter min ing blood pres sure. 33 Cen tral obe -

6 June 2002 Obe sity in Normotensives 273 sity is a well-recognized fea ture of met a bolic syn - drome re lated to the in su lin re sis tance. 13 In the cur rent study, cen tral obe sity was not a sig nif i cant in de pend - ent de ter mi nant of High Nor mal or Nor mal Group vs. Op ti mal Group. In con trast, BMI and waist cir cum fer - ence were strongly as so ci ated with blood pres sure in the Hong Kong Chi nese. 33 It re mains to be de ter mined if gen eral obe sity is a better pre dic tor than cen tral obe - sity of the de vel op ment of hy per ten sion. Our pre vi ous study by tech nique of fac tor anal y sis has re vealed a gen der-difference in the re la tion be - tween hy per ten sion and in su lin re sis tance. 32 Such dif - fer ence is also pos si ble in the de vel op ment of hy per - ten sion since higher lev els of uric acid, blood urea ni - tro gen, and creatinine in the High Nor mal and Nor mal groups were found only in fe male but not in male. Al - though some ep i de mi o log i cal stud ies sug gested uric acid as a risk fac tor of hy per ten sion as so ci ated mor - bidity, 34 hyperuricemia may pos si bly be a later man i - fes ta tion re lated to im paired re nal per fu sion caused by hypertension. 35 In con clu sion, the ap pli ca tion of JVC VI clas si fi - ca tion for the normotensives Chi nese re vealed dis tinct risk fac tor pro files for the dif fer ent blood pres sure cat - e go ries. Obe sity was the most im por tant pre dic tor of higher blood pres sure cat e go ries. There fore, weight re duc tion should be in cor po rated in any pro grams that are de signed to pre vent the de vel op ment of hy per ten - sion in the normotensives. Acknowledgements This study was sup ported by the grants from the Na tional Sci ence Coun cil, R.O.C. (NSC B and NSC B ) and the Yen Tjing Ling Med i cal Foun da tion. References 1. Yang MC, Huang IC. 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