Genetically elevated C-reactive protein and ischemic vascular disease

Area of Science:

• Cardiovascular Medicine
• Genetics
• Biomarkers

Background:

• Elevated C-reactive protein (CRP) is linked to increased risks of ischemic heart disease (IHD) and ischemic cerebrovascular disease (ICVD).
• The causal relationship between CRP levels and these vascular diseases requires further investigation.

Purpose of the Study:

• To determine if elevated C-reactive protein (CRP) levels causally increase the risk of ischemic heart disease (IHD) and ischemic cerebrovascular disease (ICVD).
• To investigate the association between CRP gene polymorphisms and the risk of ischemic vascular diseases.

Main Methods:

• Studied 10,276 individuals in a general population cohort and 31,992 in a cross-sectional study.
• Compared 2238 IHD patients and 612 ICVD patients with respective controls.
• Measured high-sensitivity CRP levels and genotyped CRP and apolipoprotein E polymorphisms.

Main Results:

• Individuals with CRP levels >3 mg/L had 1.6x IHD risk and 1.3x ICVD risk compared to those with CRP <1 mg/L.
• CRP polymorphisms increased CRP levels by up to 64%, theoretically predicting up to 32% increased IHD risk.
• However, CRP polymorphisms were not directly associated with increased ischemic vascular disease risk, unlike apolipoprotein E genotypes.

Conclusions:

• CRP gene polymorphisms are associated with significant increases in CRP levels.
• Despite elevated CRP levels, CRP gene polymorphisms are not independently associated with an increased risk of ischemic vascular disease.
• Apolipoprotein E genotypes, however, are linked to both cholesterol levels and IHD risk.