Association of Circulating Monocyte Chemoattractant Protein–1 Levels With Cardiovascular Mortality

Abstract

Human genetics and studies in experimental models support a key role of monocyte-chemoattractant protein-1 (MCP-1) in atherosclerosis. Yet, the associations of circulating MCP-1 levels with risk of coronary heart disease and cardiovascular death in the general population remain largely unexplored. OBJECTIVE To explore whether circulating levels of MCP-1 are associated with risk of incident coronary heart disease, myocardial infarction, and cardiovascular mortality in the general population.DATA SOURCES AND SELECTION Population-based cohort studies, identified through a systematic review, that have examined associations of circulating MCP-1 levels with cardiovascular end points.DATA EXTRACTION AND SYNTHESIS Using a prespecified harmonized analysis plan, study-specific summary data were obtained from Cox regression models after excluding individuals with overt cardiovascular disease at baseline. Derived hazard ratios (HRs) were synthesized using random-effects meta-analyses. MAIN OUTCOMES AND MEASURESIncident coronary heart disease (myocardial infarction, coronary revascularization, and unstable angina), nonfatal myocardial infarction, and cardiovascular death (from cardiac or cerebrovascular causes). RESULTSThe meta-analysis included 7 cohort studies involving 21 401 individuals (mean [SD] age, 53.7 [10.2] years; 10 012 men [46.8%]). Mean (SD) follow-up was 15.3 (4.5) years (326 392 person-years at risk). In models adjusting for age, sex, and race/ethnicity, higher MCP-1 levels at baseline were associated with increased risk of coronary heart disease (HR per 1-SD increment in MCP-1 levels: 1.06 [95% CI, 1.01-1.11]; P = .01), nonfatal myocardial infarction (HR, 1.07 [95% CI, 1.01-1.13]; P = .02), and cardiovascular death (HR, 1.12 [95% CI, 1.05-1.20]; P < .001). In analyses comparing MCP-1 quartiles, these associations followed dose-response patterns. After additionally adjusting for vascular risk factors, the risk estimates were attenuated, but the associations of MCP-1 levels with cardiovascular death remained statistically significant, as did the association of MCP-1 levels in the upper quartile with coronary heart disease. There was no significant heterogeneity; the results did not change in sensitivity analyses excluding events occurring in the first 5 years after MCP-1 measurement, and the risk estimates were stable after additional adjustments for circulating levels of interleukin-6 and high-sensitivity C-reactive protein.CONCLUSIONS AND RELEVANCE Higher circulating MCP-1 levels are associated with higher long-term cardiovascular mortality in community-dwelling individuals free of overt cardiovascular disease. These findings provide further support for a key role of MCP-1-signaling in cardiovascular disease.

Circulating Level of Monocyte Chemoattractant Protein-1 and Risk of Coronary Artery Disease: A Case–Control and Mendelian Randomization Study

“…32 Although meta-analysis revealed that higher circulating MCP-1 levels were associated with higher long- term cardiovascular mortality and increased long-term risk of stroke, its association with CAD risk was still inconsistent and few were conducted in Chinese. 11,13 The use of MR, which is less affected by issues of confounding, reverse causation and measurement error bias, is particularly useful in this context, as genetic variations closely related to the circulating level of MCP1 can be used as instrumental variables to assess their causal role in the development of CAD. 10 Previously, Georgakis et al 7 found circulating levels of MCP-1 were associated with higher risk of stroke, in particular with large-artery stroke and cardioembolic stroke.…”

“… 32 Although meta-analysis revealed that higher circulating MCP-1 levels were associated with higher long-term cardiovascular mortality and increased long-term risk of stroke, its association with CAD risk was still inconsistent and few were conducted in Chinese. 11 , 13 …”

“…6,[8][9][10][11][12] A recent meta-analysis revealed that higher circulating MCP1 levels were associated with higher longterm cardiovascular mortality. 13 Several studies also reported the association between MCP1 and CAD risk; however, few were conducted in Chinese and the results were inconsistent. [14][15][16][17][18] Given this background, the causality between circulating level of MCP1 and CAD risk is still unclear and to be addressed.…”

Usefulness of MCP-1 Chemokine in the Monitoring of Patients with Coronary Artery Disease Subjected to Intensive Dietary Intervention: A Pilot Study

“…Inflammation is a central process in the development and destabilisation of atherosclerotic plaques, leading to serious cardiovascular events such as myocardial infarction and Nutrients 2021, 13, 3047. https://doi.org/10.3390/nu13093047 https://www.mdpi.com/journal/nutrients Nutrients 2021, 13, 3047 2 of 16 stroke [1][2][3]. A number of chemokines is involved in the complex process of atherosclerotic plaque formation to recruit of various leukocytes, such as monocytes, macrophages and T lymphocytes, to the site of developing atheroma [4].…”

Genetic Variants, Circulating Level of MCP1 with Risk of Chronic Obstructive Pulmonary Disease: A Case-Control Study

“…[8][9][10][11][12][13] The circulating level of MCP1 has been linked to cardiovascular mortality, stroke, cancers, and atrial fibrillation. [14][15][16][17][18] Genetic polymorphisms of the MCP1 gene have also been explored for their associations with various inflammation related diseases and phenotypes, including chronic periodontitis in end-stage renal disease, obstructive sleep apnea syndrome, diabetic retinopathy in type 2 diabetes mellitus, rheumatoid arthritis, tuberculosis, lupus nephritis, coronary artery disease, and COPD. [19][20][21][22][23][24][25][26] The most studies of SNPs included SNP rs1024611 (−2518 A>G), rs2857656 (−362 G>C), and rs4586 (Cys35Cys).…”