hs-CRP as a risk assessment tool for cardiovascular disease

hs-CRP as a risk assessment tool for cardiovascular disease

It is often mentioned that almost half of first cardiovascular events occur in individuals with no known risk factors. C-reactive protein (CRP) which is usually considered as an inflammatory marker, has emerged as an important cardiovascular risk marker as well. CRP is equivalent to LDL cholesterol (low density lipoprotein cholesterol) as a risk marker. Being an inflammatory marker, high CRP levels also indicate the possibility of plaque rupture leading to coronary thrombosis and myocardial infarction [1].

The current high sensitivity assays of CRP known in short as hs-CRP can also predict recurrent coronary events in those with known coronary artery disease. hs-CRP complements information obtained by lipid profile assessment and other methods of cardiovascular risk assessment. Statins used for lowering LDL cholesterol while reducing the risk of cardiovascular events, also brings down hs-CRP levels.

Just like multiple lipid profile assessments are useful in cardiovascular risk prediction, multiple values of hs-CRP spread over a period of time has also been useful in risk prediction. One study included over 53 thousand participants with hs-CRP measured at 3 examinations in 2006, 2008 and 2010. Cumulative exposure to hs-CRP was calculated as the weighted sum of the average hs-CRP level for each time interval [2].

Participants with hs-CRP less than 3.0 mg/L in all examinations were classified as non-exposed. Those with hs-CRP 3 mg/L or more in one of the three examinations was classified as 1-exposed group. Similarly, 2-exposed and 3-exposed groups were also determined. There was a dose-response pattern with risk of cardiovascular disease and myocardial infarction as the number of years of exposure to hs-CRP increased. Those in the 3-exposed group had a higher risk than the other groups. The association between hs-CRP exposure and stroke was not found to be statistically significant.

Lipoprotein (a) is known to be an important cardiovascular risk marker, though it is not much amenable to treatment interventions like LDL cholesterol. Data from the 4,679 participants from the MESA (Multi-Ethnic Study of Atherosclerosis) was used to assess the association between Lp(a), hs-CRP and time to cardiovascular disease events. 684 events occurred during a mean follow up of 13.6 years. There was a significant interaction between Lp(a) and hs-CRP values. In those with hs-CRP less than 2 mg/L, no significant risk was observed at any level of Lp(a) right from below 50 mg/dl to over 100 mg/dl.

Isolated elevations of either Lp(a) or hs-CRP were not associated with increased risk. But the combination of elevated Lp(a) and hs-CRP was associated with significant risk. It was concluded that Lp(a) associated risk for atherosclerotic cardiovascular disease is present only in those with concomitant elevation of hs-CRP. In other words, individuals with concomitant presence of elevated Lp(a) and systemic inflammation have greater risk for atherosclerotic cardiovascular disease. These individuals merit closer surveillance and more aggressive risk management.

References

1. Yeh ET. High-sensitivity C-reactive protein as a risk assessment tool for cardiovascular disease. Clin Cardiol. 2005 Sep;28(9):408-12. doi: 10.1002/clc.4960280905. PMID: 16250263; PMCID: PMC6654463.
2. Wang A, Liu J, Li C, Gao J, Li X, Chen S, Wu S, Ding H, Fan H, Hou S. Cumulative Exposure to High-Sensitivity C-Reactive Protein Predicts the Risk of Cardiovascular Disease. J Am Heart Assoc. 2017 Oct 24;6(10):e005610. doi: 10.1161/JAHA.117.005610. PMID: 29066453; PMCID: PMC5721824.
3. Zhang W, Speiser JL, Ye F, Tsai MY, Cainzos-Achirica M, Nasir K, Herrington DM, Shapiro MD. High-Sensitivity C-Reactive Protein Modifies the Cardiovascular Risk of Lipoprotein(a): Multi-Ethnic Study of Atherosclerosis. J Am Coll Cardiol. 2021 Sep 14;78(11):1083-1094. doi: 10.1016/j.jacc.2021.07.016. PMID: 34503676; PMCID: PMC8444216.