Observed and hidden factors underlying the accumulation of chronic diseases across eight major organ systems: a longitudinal birth cohort study

IF 13.4 Q1 GERIATRICS & GERONTOLOGY

Lancet Healthy Longevity Pub Date : 2025-05-01 DOI:10.1016/j.lanhl.2025.100710

Markus J Haapanen DMedSc , Jenni Niku PhD , Tuija M Mikkola PhD , Davide L Vetrano PhD , Amaia Calderón-Larrañaga PhD , Serhiy Dekhtyar PhD , Prof Eero Kajantie DMedSc , Prof Mikaela B von Bonsdorff PhD , Prof Johan G Eriksson DMedSc

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引用次数: 0

Abstract

Background

Although individual risk factors have been linked to specific diseases, the cumulative effect of life-course factors on the accumulation of multiple chronic diseases remains unclear. This study aimed to quantify the extent to which measured and unmeasured factors explain disease burden across eight major organ systems.

Methods

We did a longitudinal analysis of a population-based birth cohort of individuals born at Helsinki University Central Hospital (Helsinki, Finland) between 1934 and 1944, who attended child welfare clinics in the city, were living in Finland in 1971, and were included in the random subsample undergoing clinical investigations between 2001 and 2004. We tracked chronic disease accumulation across eight organ systems for 30 years from hospital inpatient and outpatient records. Measured life-course factors (including age, sex, early life factors, adult lifestyle, clinical characteristics, biomarkers, and socioeconomic status) were assessed from birth until late midlife. Unmeasured factors were estimated to capture influences beyond measured factors. Multidimensional linear mixed models assessed the contribution of measured and unmeasured factors to organ-specific disease accumulation (the main outcome for this study), accounting for interdependence across organ systems.

Findings

We included data from 2003 people, collected from Jan 1, 1934, to Dec 31, 2017, in this analysis. The upper limit in disease accumulation explained by measured and unmeasured life-course factors ranged from 24·5–86·3% across eight organ systems, and was 48·3% for the total number of all diseases. Most (20·1–82·0%) of this variance was attributable to unmeasured factors. Of measured factors, clinical characteristics and biomarkers explained the largest proportion of disease accumulation (mean 30·3%; SD 15·3%; range 13·6–55·1%), followed by age (22·2%; 22·9%; 0·2–75·7%), early life factors (20·8%; 11·6%; 2·0–38·2%), lifestyle (15·8%; 10·2%; 6·8–35·6%), socioeconomic factors (8·5%; 7·1%; 0·8–17·4%), and sex (2·4%; 3·4%; 0·01–9·2%). Age, BMI, fasting blood glucose, and systolic blood pressure accelerated disease accumulation across multiple organ systems. Each decade of ageing increased disease accumulation 1·28–2·06 times. A 1-SD increase in BMI predicted a 1·28–1·72-times increase in cardiovascular, gastrointestinal, metabolic, musculoskeletal, and respiratory diseases. A 1-SD increase in fasting blood glucose predicted a 1·14–1·35-times increase in cardiovascular, metabolic, neurological, and sensory diseases; a 1-SD increase in systolic blood pressure predicted a 1·16-times increase in cardiovascular diseases and a 1·39-times increase in metabolic diseases.

Interpretation

Measured and unmeasured life-course factors explain up to three-quarters of chronic disease accumulation across systems, with the remainder probably influenced by chance. Key modifiable drivers include BMI, blood glucose, and systolic blood pressure, but substantial unexplained variance calls for further research into additional determinants.

Funding

Finska Läkaresällskapet.

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8个主要器官系统慢性病积累的观察和隐藏因素：一项纵向出生队列研究

背景：虽然个体危险因素与特定疾病有关，但生命过程因素对多种慢性疾病积累的累积效应尚不清楚。本研究旨在量化可测量和不可测量因素在多大程度上解释8个主要器官系统的疾病负担。方法：我们对1934年至1944年在赫尔辛基大学中心医院（芬兰赫尔辛基）出生的个体进行了纵向分析，这些个体曾在该市的儿童福利诊所就诊，1971年居住在芬兰，并被纳入2001年至2004年进行临床调查的随机子样本。我们从住院和门诊记录中追踪了30年来8个器官系统的慢性疾病积累。测量的生命过程因素（包括年龄、性别、早期生活因素、成人生活方式、临床特征、生物标志物和社会经济地位）从出生到中年晚期进行评估。估计未测量的因素可以捕捉到测量因素之外的影响。多维线性混合模型评估了测量和未测量因素对器官特异性疾病积累的贡献（本研究的主要结果），考虑了器官系统之间的相互依赖性。研究结果：我们在分析中纳入了从1934年1月1日到2017年12月31日收集的2003人的数据。通过测量和未测量的生命过程因素解释的疾病积累的上限在8个器官系统中为24.5 - 86.3%，在所有疾病总数中为48.3%。大部分（20.1 - 82.5%）的方差可归因于未测量的因素。在测量的因素中，临床特征和生物标志物解释了疾病积累的最大比例(平均30.3%；SD 15·3%;范围13.6 - 55.1%)，其次是年龄(22.2%；22·9%;0.2% - 75.7%)，早期生活因素(20.8%；11·6%;2·0- 38.2%)，生活方式(15.8%；10·2%;6.8% - 35.6%)，社会经济因素(8.5%；7·1%;0.8 - 17.4%)，性别(2.4%；3·4%;0·01-9·2%)。年龄、身体质量指数、空腹血糖和收缩压加速了疾病在多个器官系统的积累。衰老每10年增加疾病积累1·28-2·06倍。BMI每增加1个标准差，心血管、胃肠、代谢、肌肉骨骼和呼吸系统疾病的发病率就会增加1.28 - 1.72倍。空腹血糖升高1- sd预示心血管、代谢、神经和感觉疾病增加1.14 - 1.35倍；收缩压每升高1 sd，心血管疾病增加1.16倍，代谢性疾病增加1.39倍。解释：测量和未测量的生命过程因素解释了多达四分之三的慢性疾病跨系统积累，其余可能受偶然影响。关键的可改变的驱动因素包括BMI、血糖和收缩压，但大量无法解释的差异需要进一步研究其他决定因素。资金来源：Finska Läkaresällskapet。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Lancet Healthy Longevity GERIATRICS & GERONTOLOGY-

CiteScore

16.30

自引率

2.30%

发文量

192

审稿时长

12 weeks

期刊介绍： The Lancet Healthy Longevity, a gold open-access journal, focuses on clinically-relevant longevity and healthy aging research. It covers early-stage clinical research on aging mechanisms, epidemiological studies, and societal research on changing populations. The journal includes clinical trials across disciplines, particularly in gerontology and age-specific clinical guidelines. In line with the Lancet family tradition, it advocates for the rights of all to healthy lives, emphasizing original research likely to impact clinical practice or thinking. Clinical and policy reviews also contribute to shaping the discourse in this rapidly growing discipline.