Abstract
ObjectivesWhether high sensitivity C-reactive protein (hs-CRP) has a causal effect on coronary heart disease (CHD) is unclear. This study investigated the causal effect of hs-CRP on CHD risk using Mendelian Randomization (MR) analysis.MethodsA total of 3802 subjects were recruited in the follow-up study. Linear regression model was used to evaluate the relationship between CRP polymorphisms and hs-CRP. Survival receiver operator characteristic curve method was used to explore the cut-off of hs-CRP on CHD incidence. Cox regression model was applied to detect the association of hs-CRP with CHD by calculating the hazard ratio (HR) and 95% confidence interval (CI). Rs1205 and rs876537 in CRP were selected as instrumental variables in MR analysis.ResultsDuring a median follow-up time of 5.01 years, 98 CHD incidence was identified (47.03/104 person-years). Hs-CRP was significantly increased among rs1205 and rs876537 genotypes with r values of 0.064 and 0.066, respectively. Hs-CRP 1.08 mg/L was identified as the cut-off value with a maximum value of sensitivity and specificity on prediction of CHD. Participants with ≥1.08 mg/L of hs-CRP has a higher risk of CHD incidence than that of participants with < 1.08 mg/L, the adjusted HR (95% CI) was 1.69 (1.11–2.60) with a P value of 0.016. No significant casual association was observed between hs-CRP and CHD with a P value of 0.777.ConclusionsThe association between hs-CRP and CHD is unlikely to be causal, hs-CRP might be a predictor for incidence of CHD in general population.
Highlights
Coronary heart disease (CHD) is one of the leading global cause of death and disability
After we excluded the individuals with a history of CHD (n = 50), elder participants (n = 94) and missing measurement of high sensitivity C-reactive protein (hs-CRP) (n = 373), 3802 subjects were enrolled in the follow-up study
The age, BMI, SBP, DBP, total cholesterol (TC), TG, low-density lipoprotein cholesterol (LDL-C), GLU and proportion of hypertension in HRS were significantly higher than normal group (NG), whereas HDLC, the proportion of type 2 diabetes mellitus (T2DM), smoking and drinking were significantly lower (P < 0.05)
Summary
Coronary heart disease (CHD) is one of the leading global cause of death and disability. The current situation of rapid aging in China makes CHD become the 4th leading cause of mortality [1]. Inflammation promotes endothelial cell damage and atherogenesis, is an important risk factor for CHD in clinical [3]. Zhuang et al BMC Medical Genetics (2019) 20:170 has considerable interest in establishing whether hs-CRP has a causal role in CHD. Mendelian randomization (MR) studies utilize genetic variants (such as he-CRP) as instrumental variables (IVs) to investigate possible causal relationship between exposure and outcomes through an intermediate trait [10]. If the intermediate trait is causally linked to disease, genetic variants influencing the trait should influence disease risk. MR has been regarded as nature’s analogue of randomized controlled trials, it has been used in cardiovascular research to explore novel potential etiologic mechanisms and enhance our understanding of current therapies [13, 14]
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