From the Division of Epidemiology and Community Health, School of Public Health (D.R.J.), and the Department of Pediatrics, University of Minnesota Medical School (A.R.S., J.S.), University of Minnesota, Minneapolis; the Division of Biostatistics and Epidemiology (J.G.W., N.Z.), and the Heart Institute (E.M.U.), Cincinnati Children's Hospital Medical Center, and the Department of Pediatrics, University of Cincinnati College of Medicine (J.G.W., N.Z., E.M.U.) - both in Cincinnati; the Department of Pediatrics, University of Colorado School of Medicine, and Anschutz Medical Campus, Children's Hospital Colorado - both in Aurora (S.R.D.); the Center for Population Health Research (J.I., N.K., C.G.M., O.T.R.), the Research Center of Applied and Preventive Cardiovascular Medicine (J.I., N.K., C.G.M., O.T.R.), and the Departments of Medicine (M.J., J.S.A.V.) and Mathematics and Statistics (N.K.), University of Turku, and the Center for Population Health Research (J.I., N.K., C.G.M., O.T.R.), the Division of Medicine (M.J., J.S.A.V.), and the Department of Clinical Physiology and Nuclear Medicine (O.T.R.), Turku University Hospital, Turku, and the Department of Clinical Chemistry, Fimlab Laboratories, and the Finnish Cardiovascular Research Center, and the Faculty of Medicine and Health Technology, Tampere University, Tampere (T.L.) - all in Finland; Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS (C.G.M., A.J.V., T.D.), and the Heart Research Group, Murdoch Children's Research Institute, Melbourne, VIC (T.D.) - both in Australia; the School of Public Health and Tropical Medicine, Tulane University, New Orleans (L.A.B.); the Department of Epidemiology, College of Public Health, University of Iowa, Iowa City (T.L.B.); the Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC (R.J.P.); and the Nuffield Department of Women's and Reproductive Health, University of Oxford, Oxford, United Kingdom (T.D.).
N Engl J Med. 2022 May 19;386(20):1877-1888. doi: 10.1056/NEJMoa2109191. Epub 2022 Apr 4.
BACKGROUND: Childhood cardiovascular risk factors predict subclinical adult cardiovascular disease, but links to clinical events are unclear. METHODS: In a prospective cohort study involving participants in the International Childhood Cardiovascular Cohort (i3C) Consortium, we evaluated whether childhood risk factors (at the ages of 3 to 19 years) were associated with cardiovascular events in adulthood after a mean follow-up of 35 years. Body-mass index, systolic blood pressure, total cholesterol level, triglyceride level, and youth smoking were analyzed with the use of i3C-derived age- and sex-specific z scores and with a combined-risk z score that was calculated as the unweighted mean of the five risk z scores. An algebraically comparable adult combined-risk z score (before any cardiovascular event) was analyzed jointly with the childhood risk factors. Study outcomes were fatal cardiovascular events and fatal or nonfatal cardiovascular events, and analyses were performed after multiple imputation with the use of proportional-hazards regression. RESULTS: In the analysis of 319 fatal cardiovascular events that occurred among 38,589 participants (49.7% male and 15.0% Black; mean [±SD] age at childhood visits, 11.8±3.1 years), the hazard ratios for a fatal cardiovascular event in adulthood ranged from 1.30 (95% confidence interval [CI], 1.14 to 1.47) per unit increase in the z score for total cholesterol level to 1.61 (95% CI, 1.21 to 2.13) for youth smoking (yes vs. no). The hazard ratio for a fatal cardiovascular event with respect to the combined-risk z score was 2.71 (95% CI, 2.23 to 3.29) per unit increase. The hazard ratios and their 95% confidence intervals in the analyses of fatal cardiovascular events were similar to those in the analyses of 779 fatal or nonfatal cardiovascular events that occurred among 20,656 participants who could be evaluated for this outcome. In the analysis of 115 fatal cardiovascular events that occurred in a subgroup of 13,401 participants (31.0±5.6 years of age at the adult measurement) who had data on adult risk factors, the adjusted hazard ratio with respect to the childhood combined-risk z score was 3.54 (95% CI, 2.57 to 4.87) per unit increase, and the mutually adjusted hazard ratio with respect to the change in the combined-risk z score from childhood to adulthood was 2.88 (95% CI, 2.06 to 4.05) per unit increase. The results were similar in the analysis of 524 fatal or nonfatal cardiovascular events. CONCLUSIONS: In this prospective cohort study, childhood risk factors and the change in the combined-risk z score between childhood and adulthood were associated with cardiovascular events in midlife. (Funded by the National Institutes of Health.).
背景：儿童期心血管危险因素可预测成年后亚临床心血管疾病，但与临床事件的关联尚不清楚。
方法：在一项涉及国际儿童心血管队列（i3C）联盟参与者的前瞻性队列研究中，我们评估了在平均 35 年的随访后，成年时的心血管危险因素（年龄在 3 至 19 岁之间）是否与心血管事件有关。体重指数、收缩压、总胆固醇水平、甘油三酯水平和青少年吸烟使用 i3C 衍生的年龄和性别特异性 z 分数以及计算为五个风险 z 分数的未加权平均值的综合风险 z 分数进行分析。联合风险 z 分数（在任何心血管事件之前）用代数可比的成人联合风险 z 分数进行分析，并与儿童期危险因素联合分析。研究结果为致命性心血管事件和致命性或非致命性心血管事件，使用比例风险回归进行多次插补分析。
结果：在对 319 例发生在 38589 名参与者（49.7%为男性，15.0%为黑人；儿童就诊时的平均[±SD]年龄为 11.8±3.1 岁）的致命心血管事件的分析中，总胆固醇水平 z 分数每增加一个单位，成年时发生致命心血管事件的风险比为 1.30（95%置信区间[CI]，1.14 至 1.47），青少年吸烟（是 vs. 否）为 1.61（95%CI，1.21 至 2.13）。综合风险 z 分数每增加一个单位，发生致命心血管事件的风险比为 2.71（95%CI，2.23 至 3.29）。在对发生在 20656 名可评估该结局的参与者中的 779 例致命或非致命心血管事件的分析中，致命心血管事件的风险比及其 95%置信区间与分析结果相似。在对 13401 名（成人测量时年龄为 31.0±5.6 岁）参与者亚组中的 115 例致命心血管事件的分析中，儿童期综合风险 z 分数每增加一个单位，调整后的风险比为 3.54（95%CI，2.57 至 4.87），儿童期至成年期综合风险 z 分数变化每增加一个单位，相互调整后的风险比为 2.88（95%CI，2.06 至 4.05）。在对 524 例致命或非致命心血管事件的分析中，结果相似。
结论：在这项前瞻性队列研究中，儿童期危险因素和儿童期与成年期之间综合风险 z 分数的变化与中年心血管事件有关。（由美国国立卫生研究院资助）。
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