What is the significance of elevated High-Sensitivity C-Reactive Protein (Hs CRP) with normal lipid profiles?

From the Guidelines

Elevated high-sensitivity C-reactive protein (hs-CRP) with normal lipids indicates inflammation in the body without dyslipidemia, and the first-line approach should be lifestyle modifications, including regular exercise, a Mediterranean or DASH diet, weight management, smoking cessation, stress reduction, and limiting alcohol consumption. This finding warrants attention as it may indicate increased cardiovascular risk despite normal cholesterol levels. According to the CDC/AHA workshop on markers of inflammation and cardiovascular disease 1, hs-CRP is an independent marker of risk that may be used at the discretion of the physician in patients judged by global risk assessment to be at intermediate risk for cardiovascular disease.

The measurement of hs-CRP should be performed in a metabolically stable person without obvious inflammatory or infectious conditions, and results should be expressed as mg/L only, with cutpoints of low risk (1.0 mg/L), average risk (1.0 to 3.0 mg/L), and high risk (3.0 mg/L) corresponding to approximate tertiles of hs-CRP in the adult population 1. If hs-CRP remains above 2 mg/L despite lifestyle changes, discussion with a healthcare provider about potential low-dose statin therapy, such as rosuvastatin 5-10 mg daily or atorvastatin 10-20 mg daily, which can reduce inflammation independent of lipid effects, may be necessary.

Some key points to consider include:

• Lifestyle modifications are the first-line approach to managing elevated hs-CRP with normal lipids
• hs-CRP measurement may be useful in identifying patients at higher absolute risk than estimated by major risk factors
• The use of hs-CRP as an independent predictor of increased coronary risk is supported by evidence, but the benefits of therapy based on this strategy remain uncertain 1
• Additional testing may be needed to identify the source of inflammation, including screening for conditions like autoimmune disorders, infections, or other inflammatory diseases
• Regular monitoring of hs-CRP levels every 3-6 months is recommended to assess progress. Elevated hs-CRP reflects systemic inflammation that can damage blood vessels and increase heart attack and stroke risk even when cholesterol levels appear normal, making it an important independent cardiovascular risk marker.

From the FDA Drug Label

The JUPITER study was stopped early by the Data Safety Monitoring Board due to meeting predefined stopping rules for efficacy in rosuvastatin-treated subjects The primary end point was a composite end point consisting of the time-to-first occurrence of any of the following major CV events: CV death, nonfatal myocardial infarction, nonfatal stroke, hospitalization for unstable angina or an arterial revascularization procedure. Rosuvastatin significantly reduced the risk of major CV events (252 events in the placebo group vs. 142 events in the rosuvastatin group) with a statistically significant (p<0. 001) relative risk reduction of 44% and absolute risk reduction of 1. 2% In a post-hoc subgroup analysis of JUPITER subjects (rosuvastatin=725, placebo=680) with a hsCRP ≥2 mg/L and no other traditional risk factors (smoking, BP ≥140/90 or taking antihypertensives, low HDL-C) other than age, after adjustment for high HDL-C, there was no significant treatment benefit with rosuvastatin treatment.

The patient has elevated Hs CRP but normal lipids.

• The JUPITER study showed that rosuvastatin significantly reduced the risk of major CV events in patients with elevated hsCRP levels, but a post-hoc subgroup analysis found no significant treatment benefit in patients with elevated hsCRP and no other traditional risk factors.
• The use of rosuvastatin in patients with elevated Hs CRP but normal lipids may be considered on a case-by-case basis, taking into account the individual patient's risk factors and medical history.
• However, the FDA label does not provide clear guidance on the use of rosuvastatin in this specific patient population, and the decision to prescribe rosuvastatin should be made with caution and careful consideration of the available evidence 2.

From the Research

Elevated Hs CRP but Normal Lipids

• Elevated high-sensitivity C-reactive protein (hs-CRP) levels are associated with an increased risk of cardiovascular disease, indicating systemic inflammation 3.
• Studies have shown that statins can reduce hs-CRP levels in patients with cardiovascular diseases 4, 5, 6.
• A retrospective analysis found a significant positive correlation between hs-CRP and triglycerides, folate, serum copper, and manganese 3.
• The effects of statins on hs-CRP levels have been inconsistent, but a meta-analysis found that statins reduced the serum levels of hs-CRP in patients with cardiovascular diseases 6.

Relationship between Hs CRP and Lipids

• Abnormal lipid levels and deficiencies in certain vitamins and minerals could contribute to elevated hs-CRP levels 3.
• A study found that atorvastatin and rosuvastatin had significant effects on lowering hs-CRP levels, reducing LDL-C levels, elevating HDL-C levels, and reducing TC and TG levels in obese type 2 diabetes mellitus patients 5.
• Another study found that rosuvastatin was more effective than atorvastatin in lowering LDL-C and TC levels in obese type 2 diabetes mellitus patients 5.

Effects of Statins on Hs CRP

• Statins have anti-inflammatory effects, and several studies have reported that they can reduce hs-CRP levels 4, 5, 6.
• A systematic review and meta-analysis found that statins reduced the serum levels of hs-CRP in patients with cardiovascular diseases, with high-intensity statin treatment being more effective than moderate/low-intensity treatment 6.
• The duration of statin treatment also played a role, with treatment longer than 10 weeks decreasing hs-CRP levels 6.