Asefa Nigus G, Meirelles Osorio, Lakatta Edward, Fiorillo Edoardo, Scuteri Angelo, Cucca Francesco, Marongiu Michele, Delitala Alessandro, Schlessinger David, Launer Lenore J
Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, NIH, Baltimore, MD, United States.
Laboratory of Cardiovascular Sciences, National Institute on Aging Intramural Research Program, NIH, Baltimore, MD, United States.
Front Epidemiol. 2024 Jan 4;3:1295209. doi: 10.3389/fepid.2023.1295209. eCollection 2023.
Arterial stiffness (AS), quantified by pulse wave velocity (PWV), arises due to impaired arterial elastic tissue and smooth muscle dysfunction. We aimed to examine the longitudinal association of genetic, lipid and inflammation biomarkers with PWV and how these associations may change with aging.
We utilized genotype and four time-point biomarker data from the SardiNIA cohort [ = 6,301; mean baseline age 43.3 (SD 17.3); 58% females]. To investigate the association of PWV with genetic variants, lipid, and inflammation biomarkers, we employed linear mixed modeling, using age as the time scale. Biomarkers exhibiting significant longitudinal associations were categorized into tertiles and individuals within the second tertile or those with heterozygous alleles were excluded, leaving a cohort of 2,000 individuals. This cohort was further divided into four risk groups: low genetic and low biomarker (L-L), low genetic and high biomarker (L-H), high genetic and low biomarker (H-L), and high genetic and high biomarker risk (H-H). Subsequent analyses focused on these risk groups to assess their association to PWV with time.
Using the complete dataset, we found a significant longitudinal association of total cholesterol (TC), triglycerides (TG), fibrinogen (FGN), and total white blood cell count (TWBC) with PWV, all with < 3.33 × 10. After grouping, individuals with homogeneous risk alleles of SNP rs3742207 and high baseline TG levels (H-H group) exhibited a 1.39-fold higher PWV (m/s) (95% CI, 1.17-1.64, 1.21 × 10) compared to the L-L group. Similarly, individuals in the H-H group of rs3742207-TWBC combination showed 1.75 times higher PWV (95% CI, 1.48-0.2.07, 1.01 × 10) compared to the L-L group. Similar patterns were observed for groups based on SNP rs7152623-TWBC risk. Furthermore, these associations became more pronounced with increasing age ( < 3.33 × 10).
The longitudinal association of TG and TWBC biomarkers with PWV varied by SNPs rs3742207 and rs7152623 genotype. Further studies are warranted to investigate the function of genetics, lipids, and inflammation biomarkers on PWV change.
动脉僵硬度（AS）通过脉搏波速度（PWV）进行量化，其产生是由于动脉弹性组织受损和平滑肌功能障碍。我们旨在研究遗传、脂质和炎症生物标志物与PWV的纵向关联，以及这些关联如何随年龄变化。
我们利用了撒丁岛研究队列（SardiNIA）的基因型和四个时间点的生物标志物数据[样本量 = 6301；平均基线年龄43.3岁（标准差17.3）；58%为女性]。为了研究PWV与基因变异、脂质和炎症生物标志物之间的关联，我们采用线性混合模型，将年龄作为时间尺度。将表现出显著纵向关联的生物标志物分为三个三分位数，并排除处于第二个三分位数内的个体或具有杂合等位基因的个体，从而得到一个由2000名个体组成的队列。该队列进一步分为四个风险组：低遗传和低生物标志物组（L-L）、低遗传和高生物标志物组（L-H）、高遗传和低生物标志物组（H-L）以及高遗传和高生物标志物风险组（H-H）。随后的分析聚焦于这些风险组，以评估它们随时间与PWV的关联。
使用完整数据集，我们发现总胆固醇（TC）、甘油三酯（TG）、纤维蛋白原（FGN）和白细胞总数（TWBC）与PWV存在显著的纵向关联，所有P值均 < 3.33×10。分组后，单核苷酸多态性（SNP）rs3742207具有相同风险等位基因且基线TG水平较高的个体（H-H组）与L-L组相比，PWV（m/s）高出1.39倍（95%置信区间，1.17 - 1.64，P = 1.21×10）。同样，rs3742207 - TWBC组合的H-H组个体与L-L组相比，PWV高出1.75倍（95%置信区间，1.48 - 2.07，P = 1.01×10）。基于SNP rs7152623 - TWBC风险的组也观察到类似模式。此外，随着年龄增长（P < 3.33×10），这些关联变得更加明显。
TG和TWBC生物标志物与PWV的纵向关联因SNP rs3742207和rs7152623基因型而异。有必要进一步研究遗传、脂质和炎症生物标志物对PWV变化的作用。
