A cohort study on the association between metabolically unhealthy obesity and hypertension
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摘要:
目的 探讨代谢性肥胖与高血压发病的关系，为人群高血压防制提供理论依据。 方法 采用前瞻性队列研究设计，于2009年在江苏省宜兴市官林、徐舍2个乡镇采用整群抽样方法纳入4 128名成人进行流行病学基线调查。排除基线2 012名高血压病例，截至2020年7月对2 116名非高血压对象进行高血压发病随访。根据体重和代谢状态将研究对象分为4组：代谢正常体重正常(metabolically healthy and normal weight, MHNW)、代谢正常超重/肥胖(metabolically healthy overweight/obesity, MHO)、代谢异常体重正常(metabolically unhealthy and normal weight, MUNW)、代谢异常超重/肥胖(metabolically unhealthy overweight/obesity, MUO)。采用Cox比例风险回归模型对代谢性肥胖与高血压发病关联进行分析，进一步做分层分析、异质性检验及相加与相乘交互作用分析；排除随访第一年发病的高血压对象、排除偏瘦人群进行敏感性分析。 结果 共随访到新发高血压637例，超重肥胖及代谢异常联合相较于体重正常代谢正常的人群归因危险度(population attributable risk, PAR)及PAR%分别为17.4%、57.93%。Cox回归分析结果显示：与MHNW相比，MHO、MUNW、MUO三组的高血压发病风险增加均有统计学意义，调整后的HR(95% CI)值分别为1.29(1.08~1.56)、1.48(1.09~2.01)、1.70(1.37~2.11)，并呈风险递增的趋势(均有P < 0.001)。分层分析和异质性检验结果显示：女性MUO的高血压发病风险(调整HR：2.14)高于男性MUO(调整HR：1.22)，P异质性检验= 0.017。相乘交互作用分析结果显示：性别与代谢状态之间存在相乘交互作用，调整后的HR(95% CI)值为1.53(1.06~2.22)，P=0.024。排除随访第一年高血压发病的对象或排除偏瘦人群进行敏感性分析，关联强度无明显变化。 结论 代谢性肥胖增加人群高血压发病风险，尤其在女性人群中风险更高。因此，对超重肥胖及代谢异常相关人群进行主动健康干预预防高血压具有十分重要意义。 Abstract:Objective To explore the association between metabolically unhealthy obesity and hypertension, so as to provide theoretical basis for prevention and control of hypertension. Methods A prospective cohort study design was used to investigate the epidemiological baseline of 4 128 adults in Guanlin and Xushe towns of Yixing City, Jiangsu Province in 2009. A total of 2012 hypertensive cases were excluded at baseline and 2116 non-hypertensive subjects were followed up until July 2020. According to the weight and metabolic status, all subjects were grouped into four groups, metabolically healthy and normal weight (MHNW), metabolically healthy overweight/obesity (MHO), metabolically unhealthy and normal weight (MUNW) and metabolically unhealthy overweight/obesity (MUO). Cox proportional risk regression model was used for correlation analysis between metabolic obesity and hypertension. Stratified analysis, heterogeneity test, additive and multiplicative interaction analysis were further carried out. We also conducted sensitivity analyses for the population with developing hypertension in the first year of follow-up and the thin individuals excluded. Results 637 participants developed hypertension during followed-up. The population attributable risk (PAR) and its percentage (PAR%) of obesity and metabolically unhealthy were 17.4% and 57.93%, respectively. Compared with MHNW, the MHO, MUNW and MUO groups had significantly increased risk of hypertension, and the adjusted HR(95% CI) were 1.29 (1.08-1.56), 1.48 (1.09-2.01) and 1.70 (1.37-2.11), respectively, with increasing trends (P < 0.001). The results of stratified analysis and heterogeneity test showed that the risk of hypertension in women (adjusted HR: 2.14) was higher than that in men (adjusted HR: 1.22), and P for heterogeneity test was 0.017. There was a multiplicative interaction between gender and metabolic status, and the adjusted HR(95% CI) was 1.53 (1.06-2.22), P=0.024. No significant change was detected for the association in the sensitivity analysis. Conclusions The metabolically unhealthy obesity significantly increased the risk of hypertension and particularly in women. Therefore, the initiative health intervention for the population with overweight, obesity and metabolic disorders may effectively reduce the risk of hypertension. -
Key words:
- Metabolically unhealthy obesity /
- Hypertension /
- Cohort study /
- Interaction
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表 1 总人群及不同代谢状况与体重分组基本情况[n(%)]
Table 1. Basic information of the whole population and different metabolical and weight groups [n(%)]
人群特征 总人群(N=2 116) MHNW(n=1 030) MHO(n=640) MUNW(n=146) MUO(n=300) H/χ2值 P值 年龄a(岁) 57.65(50.83, 64.46) 57.83(51.46, 65.75) 56.82(50.82, 62.80) 56.76(49.11, 63.81) 56.75(50.75, 64.74) 5.68 0.128 性别 15.81 0.001 男 853(40.31) 459(44.56) 239(37.34) 51(34.93) 104(34.67) 女 1 263(59.69) 571(55.44) 401(62.66) 95(65.07) 196(65.33) 吸烟者 525(24.81) 297(28.83) 129(20.16) 29(19.86) 70(23.33) 18.64 < 0.001 饮酒者 468(22.12) 244(23.69) 119(18.59) 28(19.18) 77(25.67) 9.02 0.029 BMI a(kg/m2) 23.42(21.49, 25.85) 21.62(20.06, 22.72) 25.96(24.93, 27.41) 22.53(21.62, 23.31) 26.45(25.39, 27.85) 1 580.97 < 0.001 WC a(cm) 82.00(76.00, 88.00) 77.00(73.00, 82.00) 86.00(80.25, 90.00) 84.00(80.75, 90.00) 90.00(85.00, 96.00) 730.16 < 0.001 SBP a(mm Hg) 127.00(119.00, 133.00) 125.00(115.00, 132.00) 125.00(119.00, 130.00) 132.50(128.75, 137.25) 130.00(124.00, 135.00) 123.57 < 0.001 DBP a(mm Hg) 80.00(76.00, 83.00) 79.00(74.00, 82.50) 80.00(76.13, 82.00) 82.00(78.00, 86.25) 81.00(78.00, 85.00) 87.96 < 0.001 TC a(mmol/L) 4.77(4.17, 5.37) 4.69(4.12, 5.29) 4.85(4.27, 5.40) 4.80(4.11, 5.52) 4.85(4.14, 5.66) 12.21 < 0.001 TG a(mmol/L) 1.19(0.83, 1.83) 0.99(0.73, 1.40) 1.23(0.89, 1.70) 2.26(1.34, 3.10) 2.32(1.39, 3.23) 411.07 < 0.001 HDL-C a(mmol/L) 1.33(1.14, 1.55) 1.42(1.21, 1.62) 1.32(1.15, 1.52) 1.17(0.97, 1.52) 1.14(0.96, 1.36) 190.74 < 0.001 LDL-C a(mmol/L) 2.59(2.18, 3.05) 2.53(2.14, 2.99) 2.71(2.32, 3.15) 2.51(2.03, 3.02) 2.63(2.11, 3.11) 24.50 < 0.001 FPG a(mmol/L) 5.22(4.78, 5.67) 5.11(4.71, 5.49) 5.17(4.75, 5.50) 5.71(5.02, 6.32) 5.83(5.21, 6.62) 203.39 < 0.001 脑卒中史 49(2.32) 29(2.82) 8(1.25) 3(2.05) 9(3.00) 6.64 0.301 冠心病史 50(2.36) 21(2.04) 18(2.81) 3(2.05) 8(2.67) 3.00 0.799 高血压史 408(19.28) 189(18.35) 87(13.59) 45(30.82) 87(29.00) 44.58 < 0.001 糖尿病史 68(3.21) 24(2.33) 9(1.41) 6(4.11) 29(9.67) 49.85 < 0.001 注：a采用[M(P25, P75)]表示。 
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表 2 不同代谢体重分组与高血压发病的关联分析
Table 2. Analyses of association between different metabolical and weight groups and the risk of hypertension
随访信息 模型 MHNW(n=1 030) MHO(n=640) MUNW(n=146) MUO(n=300) P值a 发病人数 268 199 50 120 随访人年 9 082.95 5 496.80 1 184.56 2 443.58 发病密度(/万人年) 295.06 362.03 422.10 491.08 HR (95% CI)值 模型1 1.00 1.21(1.01~1.46) 1.42(1.05~1.92) 1.65(1.33~2.05) < 0.001 模型2 1.00 1.29(1.07~1.55) 1.48(1.10~2.01) 1.72(1.39~2.14) < 0.001 模型3 1.00 1.29(1.08~1.56) 1.48(1.09~2.01) 1.70(1.37~2.11) < 0.001 注：模型1：不调整变量；模型2：调整年龄、性别；模型3：调整年龄、性别、吸烟、饮酒、高血压家族史；a趋势性检验。
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表 3 不同代谢体重分组与高血压发病关联的分层分析及异质性检验
Table 3. Stratified analyses and heterogeneity test of association between different metabolical and weight groups and hypertension
分层因素 MHNW (N=1 030) MHO(n=640) MUNW(n=146) MUO(n=300) HR(95% CI)值a P值b HR(95% CI)值a P值b HR(95% CI)值a P值b 年龄(岁) ＜60 1.00 1.35(1.04~1.76) 0.581 1.32(0.85~2.05) 0.328 1.78(1.31~2.41) 0.824 ≥60 1.00 1.22(0.94~1.58) 1.79(1.18~2.73) 1.69(1.23~2.32) 性别 男 1.00 1.28(0.97~1.68) 0.753 1.30(0.79~2.16) 0.467 1.22(0.85~1.76) 0.017 女 1.00 1.36(1.05~1.75) 1.65(1.12~2.43) 2.14(1.62~2.83) 吸烟 否 1.00 1.29(1.04~1.60) 0.663 1.58(1.13~2.22) 0.544 1.86(1.45~2.39) 0.215 是 1.00 1.42(0.98~2.05) 1.23(0.60~2.56) 1.34(0.86~2.10) 饮酒 否 1.00 1.28(1.03~1.59) 0.630 1.55(1.11~2.18) 0.661 1.93(1.51~2.48) 0.069 是 1.00 1.42(0.98~2.06) 1.31(0.65~2.62) 1.20(0.77~1.88) 注：a调整年龄、性别、吸烟、饮酒、高血压家族史；b异质性检验结果。
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表 4 性别与代谢性肥胖对高血压发病的相加及相乘交互作用
Table 4. The additive and multiplicative interaction of sex and metabolically unhealthy obesity on the incidence of hypertension
模型 相加交互作用 相乘交互作用 RERI (95% CI)值 P值 HR(95% CI)值 P值 模型1 0.50(0.12~0.89) 0.011 1.68(1.16~2.44) 0.006 模型2 0.06(-0.52~0.64) 0.844 1.51(1.04~2.19) 0.029 模型3 0.06(-0.52~0.64) 0.842 1.53(1.06~2.22) 0.024
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表 5 不同代谢体重分组与高血压发病的敏感性分析
Table 5. Sensitivity analysis of different metabolic and weight groups and hypertension
排除对象 模型 MHNW HR(95% CI)值 P值 MHO MUNW MUO值 排除随访第一年高血压发病 模型1 1.00 1.16(0.96~1.41) 1.35(0.98~1.84) 1.68(1.35~2.09) < 0.001 模型2 1.00 1.24(1.03~1.50) 1.41(1.03~1.94) 1.75(1.41~2.18) < 0.001 模型3 1.00 1.24(1.03~1.51) 1.42(1.03~1.94) 1.74(1.40~2.17) < 0.001 排除偏瘦人群重新分组 模型1 1.00 1.23(1.02~1.48) 1.40(1.02~1.90) 1.68 (1.35~2.08) < 0.001 模型2 1.00 1.29(1.07~1.56) 1.44(1.06~1.97) 1.72(1.38~2.14) < 0.001 模型3 1.00 1.29(1.07~1.56) 1.44(1.06~1.97) 1.69(1.36~2.11) < 0.001 注：模型1：不调整变量；模型2：调整年龄、性别；模型3：调整年龄、性别、吸烟、饮酒、高血压家族史。
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