Relationship between serum homocysteine, fibrinogen, lipoprotein-a level, and peripheral arterial disease: a dose–response meta-analysis

Abstract

Aim At present, the relationship between serum homocysteine (Hcy), fibrinogen (FIB), lipoprotein-a (LPa), and PAD is uncertain, and there has been no meta-analysis to establish the dose–response relationship between their exposure levels and PAD. Methods and results Relevant literature published in PubMed, Embase, and Web of Science was retrieved. The robust error meta-regression method was used to assess the linear and non-linear dose–response relationship between exposure level and PAD risk. A total of 68 articles, involving 565,209 participants, were included. Combined with continuous variables, the serum Hcy, FIB, and LPa levels of PAD patients were significantly higher than those of healthy individuals. The odds ratios (ORs) of PAD for individuals with high Hcy, FIB, and LPa levels compared with those with low levels were 1.47, 1.14, and 1.76, respectively. The study also showed that circulating Hcy, FIB, and LPa were significantly elevated in patients with PAD compared with controls. The level of Hcy and the risk of PAD presented a U-shaped distribution. The nonlinear dose–response model showed that each 1 μmol/L increase in serum Hcy increased the risk of PAD by 7%. Similarly, for each 10 mg/dL FIB and 10 mg/dL LPa increases, the risk of PAD increased by 3% and 6%, respectively. Conclusions This meta-analysis provided evidence that elevated Hcy, PIB, and LPa levels may increase the risk of PAD, and the risk of PAD increases with the increase in serum exposure within a certain range. By controlling Hcy level, the incidence of PAD may be reduced to control the PAD growing epidemic. Trial registration number: PROSPERO (CRD42021250501), https://www.crd.york.ac.uk/prospero/

Association of plasma homocysteine with peripheral arterial disease in the hypertensive adults: A cross‐sectional study

“… 19 Moreover, a multi‐population meta‐analysis of 11 687 patients showed higher plasma Hcy levels in patients with PAD compared with healthy individuals. 28 Consistent with the conclusions of our study, these studies all showed a significant association between plasma Hcy and PAD. However, Ridker and coworkers did not find a clear association between plasma Hcy and PAD in a nested case‐control study of 240 United States male physicians.…”

“…Similarly, a case‐control study by Rong and coworkers also showed a higher risk of PAD with high plasma Hcy levels in Chinese adults 19 . Moreover, a multi‐population meta‐analysis of 11 687 patients showed higher plasma Hcy levels in patients with PAD compared with healthy individuals 28 . Consistent with the conclusions of our study, these studies all showed a significant association between plasma Hcy and PAD.…”

Early symptoms and signs of bony and brain lesions associated with hyperhomocysteinemia: Evidence with scintigraphic images of skeleton and brain

“…It has been provided that elevated Hcy may raise the risk of Peripheral Artery Disease (PAD). Well controlling the level of Hcy could potentially reduce the incidence of PAD and help address the growing epidemic of PAD [9]. Furthermore, the increased total Hcy level has been categorized as a contributing factor to borderline Ankle-Brachial Index (ABI).…”

“…HHcy is a disorder involving a wide variety of diseases, it arises when the metabolism of Hcy is disrupted due to deficiencies in B-vitamins, genetic defects, or other pathophysiological conditions [5,6]. HHcy have been convincingly linked to cardiovascular, cerebrovascular, neurodegenerative, and thromboembolic diseases, and also been found to have a close relationship with peripheral artery diseases [4,[7][8][9].…”

Assessment of Apolipoprotein(a) Isoform Size Using Phenotypic and Genotypic Methods

“…Lp(a) is a form of a low-density lipoprotein (LDL) and is an established and genetically determined risk factor for atherosclerosis, coronary artery disease (CAD), stroke, and aortic stenosis [ 1 , 2 ]. Moreover, high plasma levels of Lp(a) nearly double the risk of developing peripheral artery disease [ 3 ]. Mendelian studies also associate a high Lp(a) with a mildly though significantly higher risk of developing atrial fibrillation.…”