Association of C-reactive Protein with Cardiovascular Outcomes: A Mendelian Randomization Study in the Japanese...

Area of Science:

• Cardiovascular Epidemiology
• Genetic Epidemiology
• Biomarkers

Background:

• C-reactive protein (CRP) is linked to cardiovascular disease (CVD) risk in observational studies.
• The causal relationship between CRP and specific cardiovascular outcomes remains uncertain.

Purpose of the Study:

• To investigate the potential causal effect of C-reactive protein (CRP) on cardiovascular outcomes.
• To examine the causal association between genetically predicted CRP levels and ischemic stroke, atrial fibrillation, arrhythmia, and congestive heart failure.

Main Methods:

• Two-sample Mendelian randomization (MR) analysis using summary statistics from the Japanese Encyclopedia of Genetic association by Riken (JENGER).
• Four single-nucleotide polymorphisms (SNPs) associated with CRP levels were utilized as instrumental variables.
• Inverse-variance weighted (IVW), penalized weighted median, and weighted median methods were employed for MR estimation, with MR-Egger regression assessing pleiotropy.

Main Results:

• No significant causal association was detected between genetically determined CRP levels and ischemic stroke, atrial fibrillation, or arrhythmia across all MR methods.
• The IVW method suggested a potential causal link between CRP and congestive heart failure (OR: 1.337, P=0.046), though not consistently supported by other methods.
• No substantial evidence of pleiotropy or heterogeneity was observed in the analyses.

Conclusions:

• Mendelian randomization analysis provides suggestive evidence for a causal association between C-reactive protein and congestive heart failure.
• No causal relationship was established between CRP and ischemic stroke, atrial fibrillation, or arrhythmia.
• Further research is recommended to confirm the link between CRP and congestive heart failure.