National Clinician Scholars Program, Yale School of Medicine, New Haven, CT, USA.
Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA.
Int J Vitam Nutr Res. 2023 Apr;93(2):99-110. doi: 10.1024/0300-9831/a000709. Epub 2021 May 24.
Lipoprotein(a)(Lp[a]) is a low-density lipoprotein-cholesterol (LDL-C)-like particle with potent pro-atherothrombotic properties. The association of Lp(a) with several circulating factors, including vitamins, remains unresolved. We performed an observational analysis using the National Health and Nutrition Examination Survey III cohort, a cohort used to monitor the nutrition status of US-citizens. We used multivariable linear regression to test associations of Lp(a) and LDL-C with levels of serum vitamins and minerals and whole-blood lead. Analyses controlled for factors known to associate with Lp(a) (age, sex, race/ethnicity, statin use, hemoglobin A1c, body mass index, hypertension, diabetes, glomerular filtration rate, alcohol intake, and saturated fat intake). LDL-C was corrected for Lp(a) mass. Multiple sensitivity tests were performed, including considering factors as categorical variables (deficient, normal, elevated). Among 7,662 subjects, Lp(a) correlated (β-coefficient) positively (change per 1 conventional unit increase) with carotenoids (lycopene (0.17(0.06,0.28), p=0.005), lutein (0.19(0.07,0.30), p=0.002), β-cryptoxanthin (0.21(0.05,0.37), p=0.01), β-carotene (0.05(0.02,0.09), p=0.003), and α-carotene (0.15(0.01,0.30), p=0.04)) and lead (0.54(0.03,1.05), p=0.04) levels when tested as continuous variables. LDL-C had similar associations. Lp(a) did not associate with vitamins A, B12, C, or E retinyl esters, folate, RBC-folate, selenium, ferritin, transferrin saturation, or calcium. With factors as categorical variables, Lp(a) but not LDL-C negatively associated with elevated vitamin B12 (-5.41(-9.50, -1.53), p=0.01) and folate (-2.86(-5.09, -0.63), p=0.01). In conclusion, Lp(a) associated similarly to LDL-C when vitamins, minerals, and lead were tested as continuous variables, while only Lp(a) correlated with vitamin B12 and folate when tested as categorical variables. These observations are hypotheses generating and require further studies to determine causality.
脂蛋白(a)(Lp[a])是一种类似于低密度脂蛋白胆固醇(LDL-C)的颗粒，具有很强的促动脉粥样硬化血栓形成作用。Lp(a)与包括维生素在内的几种循环因子的关联仍未得到解决。我们使用国家健康和营养检查调查 III 队列进行了一项观察性分析，该队列用于监测美国公民的营养状况。我们使用多变量线性回归来测试 Lp(a)和 LDL-C 与血清维生素和矿物质以及全血铅水平的关系。分析控制了与 Lp(a)相关的已知因素(年龄、性别、种族/民族、他汀类药物使用、糖化血红蛋白、体重指数、高血压、糖尿病、肾小球滤过率、饮酒量和饱和脂肪摄入量)。LDL-C 经 Lp(a)质量校正。进行了多次敏感性测试，包括将因素视为分类变量(缺乏、正常、升高)。在 7662 名受试者中，Lp(a)与类胡萝卜素(番茄红素(0.17(0.06,0.28)，p=0.005)、叶黄素(0.19(0.07,0.30)，p=0.002)、β-隐黄质(0.21(0.05,0.37)，p=0.01)、β-胡萝卜素(0.05(0.02,0.09)，p=0.003)和α-胡萝卜素(0.15(0.01,0.30)，p=0.04)呈正相关(每增加一个常规单位的变化β-系数)，当作为连续变量测试时，Lp(a)与铅(0.54(0.03,1.05)，p=0.04)水平相关。LDL-C 也有类似的关联。Lp(a)与维生素 A、B12、C 和 E 视黄醇酯、叶酸、RBC-叶酸、硒、铁蛋白、转铁蛋白饱和度或钙不相关。当作为分类变量时，Lp(a)而不是 LDL-C 与升高的维生素 B12(-5.41(-9.50, -1.53)，p=0.01)和叶酸(-2.86(-5.09, -0.63)，p=0.01)呈负相关。总之，当维生素、矿物质和铅作为连续变量进行测试时，Lp(a)与 LDL-C 的关联相似，而只有 Lp(a)与维生素 B12 和叶酸作为分类变量测试时呈正相关。这些观察结果是产生假说的，并需要进一步的研究来确定因果关系。
