Janus Scott E, Durieux Jared C, Hajjari Jamal, Carneiro Herman, McComsey Grace A
Harrington Heart and Vascular Institute.
Clinical Research Center.
AIDS. 2022 Apr 1;36(5):647-655. doi: 10.1097/QAD.0000000000003149.
People with HIV (PWH) experience increased systemic inflammation and monocyte activation, leading to increased risk of cardiovascular events (death, stroke, and myocardial infarction) and higher coronary artery calcium scores (CACs). Vitamins D and K2 have significant anti-inflammatory effects; in addition, vitamin K2 is involved in preventing vascular calcifications in the general population. The roles of vitamins D and K in increased coronary calcifications in successfully treated PWH is less understood.
We prospectively recruited 237 PWH on antiretroviral treatment (ART) and 67 healthy controls. CACs were derived from noncontrast chest computed tomography (CT) and levels of 25-hydroxyvitamin D (vitamin D) and inactive vitamin K-dependent dephosphorylated-uncarboxylated matrix Gla protein (dp-uc MGP, marker of vitamin K deficiency) were measured in plasma during a fasting state. The relationship between inflammation markers, dp-uc MGP, and vitamin D on CACs were estimated using zero-inflated negative binomial regression. Adjusted models included 25(OH)D, MGP, sex, race, age, and markers of inflammation or monocyte activation.
Overall, controls had lower median age (45.8 vs. 48.8; P = 0.03), a larger proportion of female individuals (55.2 vs. 23.6%; P < 0.0001), and nonwhite (33.8 vs. 70%; P < 0.0001). Among PWH, less than 1% had detectable viral load and the median CD4+ cell count was 682 (IQR: 473.00-899.00). 62.17% of the participants had zero CACs and 51.32% were vitamin D-deficient (<20 ng/ml). There was no difference in detectable CACs (P = 0.19) or dp-uc MGP (P = 0.42) between PWH and controls. In adjusted models, PWH with nonzero CACs have three times greater expected CAC burden compared with controls. Every 1% increase in MGP (worse K status) decreases the probability of having CACs equal to zero by 21.33% (P = 0.01). Evidence suggests that the effects of 25(OH)D and MGP are inflammation-mediated, specifically through sVCAM, TNF-αRI, and TNF-αRII.
Vitamin K deficiency is a modifiable preventive factor against coronary calcification in PWH. Further research should determine whether vitamin K supplementation would reduce systemic inflammation, vascular calcification, and risk of cardiovascular events in PWH.
人类免疫缺陷病毒感染者（PWH）存在全身炎症增加和单核细胞活化的情况，这导致心血管事件（死亡、中风和心肌梗死）风险增加以及冠状动脉钙化评分（CACs）升高。维生素D和K2具有显著的抗炎作用；此外，维生素K2参与预防普通人群的血管钙化。维生素D和K在成功接受治疗的PWH冠状动脉钙化增加中的作用尚不清楚。
我们前瞻性招募了237名接受抗逆转录病毒治疗（ART）的PWH和67名健康对照者。通过非增强胸部计算机断层扫描（CT）获得CACs，并在空腹状态下测量血浆中25-羟基维生素D（维生素D）水平和无活性维生素K依赖性去磷酸化未羧化基质Gla蛋白（dp-uc MGP，维生素K缺乏的标志物）水平。使用零膨胀负二项回归估计炎症标志物、dp-uc MGP和维生素D与CACs之间的关系。校正模型包括25(OH)D、MGP、性别、种族、年龄以及炎症或单核细胞活化标志物。
总体而言，对照组的年龄中位数较低（45.8岁对48.8岁；P = 0.03），女性比例更高（55.2%对23.6%；P < 0.0001），非白人比例更高（33.8%对70%；P < 0.0001）。在PWH中，不到1%的人病毒载量可检测到，CD4+细胞计数中位数为682（四分位间距：473.00 - 899.00）。62.17%的参与者CACs为零，51.32%的人维生素D缺乏（<20 ng/ml）。PWH和对照组在可检测到的CACs（P = 0.19）或dp-uc MGP（P = 0.42）方面没有差异。在校正模型中，有非零CACs的PWH的预期CAC负担是对照组的三倍。MGP每增加1%（维生素K状态更差），CACs等于零的概率降低21.33%（P = 0.01）。有证据表明25(OH)D和MGP的作用是由炎症介导的，特别是通过可溶性血管细胞黏附分子（sVCAM）、肿瘤坏死因子-α受体I（TNF-αRI）和肿瘤坏死因子-α受体II（TNF-αRII）。
维生素K缺乏是PWH冠状动脉钙化的一个可改变的预防因素。进一步的研究应确定补充维生素K是否会降低PWH的全身炎症、血管钙化和心血管事件风险。
