Marinello Davide, Favero Chiara, Albetti Benedetta, Barbuto Davide, Vigna Luisella, Pesatori Angela Cecilia, Bollati Valentina, Ferrari Luca
EPIGET LAB, Department of Clinical Sciences and Community Health, Dipartimento di Eccellenza 2024-2027, University of Milan, 20122 Milan, Italy.
Occupational Health Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy.
Biomedicines. 2024 Jul 23;12(8):1631. doi: 10.3390/biomedicines12081631.
: Cardiovascular diseases stand as the leading global cause of mortality. Major modifiable risk factors encompass overweight/obese conditions, high blood pressure, elevated LDL cholesterol, diabetes, smoking, secondhand smoke exposure, unhealthy diet, and physical inactivity. In the present study, we explored the relationship between cardiovascular risk factors and epigenetic age (DNAm age), an estimate reflecting an individual's actual physiological functionality and overall health. Additionally, we assessed the association between DNAm age acceleration and cardiovascular risk, as evaluated through the Framingham risk score (FRS). : The study includes 190 subjects with overweight/obese conditions. We calculated their DNAm age using Zbieć-Piekarska et al.'s DNAm age estimator on five sets of CpGs analyzed in the peripheral leucocytes. Linear regression models were employed to test the associations. : Various parameters contributing to increased cardiovascular risk were associated with DNAm age acceleration, such as systolic blood pressure (β = 0.045; SE = 0.019; = 0.019), heart rate (β = 0.096; SE = 0.032; = 0.003), blood glucose (β = 0.025; SE = 0.012; = 0.030), glycated hemoglobin (β = 0.105; SE = 0.042; = 0.013), diabetes (β = 2.247; SE = 0.841; = 0.008), and menopausal conditions (β = 2.942; SE = 1.207; = 0.016), as well as neutrophil (β = 0.100; SE = 0.042; = 0.018) and granulocyte (β = 0.095; SE = 0.044; = 0.033) counts. Moreover, DNAm age acceleration raised the FRS (∆% 5.3%, 95% CI 0.8; 9.9, = 0.019). : For the first time, we report that cardiovascular risk factors accelerated DNAm age in a selected population of hypersusceptible individuals with overweight or obesity. Our results highlight the potential of DNAm age acceleration as a biomarker of cumulative effects in cardiovascular risk assessment.
心血管疾病是全球主要的死亡原因。主要的可改变风险因素包括超重/肥胖、高血压、低密度脂蛋白胆固醇升高、糖尿病、吸烟、接触二手烟、不健康饮食和身体活动不足。在本研究中，我们探讨了心血管风险因素与表观遗传年龄（DNA甲基化年龄）之间的关系，表观遗传年龄是反映个体实际生理功能和整体健康状况的一个指标。此外，我们还评估了DNA甲基化年龄加速与心血管风险之间的关联，该关联通过弗雷明汉风险评分（FRS）进行评估。
该研究纳入了190名超重/肥胖受试者。我们使用Zbieć-Piekarska等人的DNA甲基化年龄估计器，根据在外周血白细胞中分析的五组CpG计算他们的DNA甲基化年龄。采用线性回归模型来检验这些关联。
导致心血管风险增加的各种参数与DNA甲基化年龄加速相关，如收缩压（β = 0.045；标准误 = 0.019；P = 0.019）、心率（β = 0.096；标准误 = 0.032；P = 0.003）、血糖（β = 0.025；标准误 = 0.012；P = 0.030）、糖化血红蛋白（β = 0.105；标准误 = 0.042；P = 0.013）、糖尿病（β = 2.247；标准误 = 0.841；P = 0.008）、绝经状态（β = 2.942；标准误 = 1.207；P = 0.016），以及中性粒细胞（β = 0.100；标准误 = 0.042；P = 0.018）和粒细胞（β = 0.095；标准误 = 0.044；P = 0.033）计数。此外，DNA甲基化年龄加速提高了FRS（变化百分比5.3%，95%置信区间0.8；9.9，P = 0.019）。
我们首次报告，在选定的超重或肥胖高敏个体人群中，心血管风险因素加速了DNA甲基化年龄。我们的结果突出了DNA甲基化年龄加速作为心血管风险评估中累积效应生物标志物的潜力。
