Are there blood markers for assessing heart attack risk?

Blood Markers for Heart Attack Risk Assessment

Yes, several blood markers can assess heart attack risk, with high-sensitivity C-reactive protein (hs-CRP) showing the most promise for refining risk assessment in patients at intermediate cardiovascular risk, though traditional lipid markers remain the foundation of risk prediction. 1

Primary Blood Markers for Risk Assessment

Traditional Lipid Markers (Foundation of Risk Assessment)

• Total cholesterol, LDL cholesterol, HDL cholesterol, and the total cholesterol to HDL ratio remain the cornerstone of cardiovascular risk prediction and should be measured first in all patients 1, 2
• The ratio of total cholesterol to HDL cholesterol independently predicts cardiovascular events with a relative risk of 1.4 for highest versus lowest quartile 2
• Apolipoprotein B (ApoB) levels ≥130 mg/dL constitute a significant risk-enhancing factor, though routine measurement is of uncertain value for widespread population screening 1

Inflammatory Markers

High-Sensitivity C-Reactive Protein (hs-CRP):

• hs-CRP may be measured as part of refined risk assessment specifically in patients with moderate or intermediate cardiovascular risk profiles 1
• hs-CRP is the strongest inflammatory predictor among novel biomarkers, with a relative risk of 4.4 for cardiovascular events comparing highest to lowest quartile 2
• In multivariate analysis, hs-CRP independently predicts risk (relative risk 1.5) even after accounting for lipid levels 2
• hs-CRP should NOT be measured in asymptomatic low-risk individuals or already high-risk patients, as it adds minimal value at these extremes 1

Fibrinogen:

• May be measured as part of refined risk assessment in patients with moderate CVD risk profiles 1
• Should not be measured in low-risk or high-risk patients for 10-year CVD risk assessment 1

Thrombotic Markers

Homocysteine:

• May be measured as part of refined risk assessment in patients with unusual or moderate CVD risk profiles 1
• Shows modest predictive value (relative risk 2.0 for highest versus lowest quartile) 2
• Should NOT be measured to monitor CVD risk prevention, as intervention studies using B vitamins to reduce homocysteine have proven ineffective at reducing cardiovascular events 1

Lipoprotein-associated Phospholipase A2 (LpPLA2):

• May be measured in patients at high risk of recurrent acute atherothrombotic events 1
• Limited evidence for primary prevention screening 1

Renal Function Markers

• Creatinine (or estimated GFR) and microalbuminuria were evaluated but found to be of uncertain value for routine cardiovascular risk assessment 1

Clinical Application Algorithm

Step 1: Calculate Baseline Risk

• Measure traditional lipid panel (total cholesterol, LDL, HDL, triglycerides) in all patients 1, 2
• Calculate 10-year ASCVD risk using validated risk equations 1

Step 2: Identify Candidates for Additional Biomarker Testing

Consider hs-CRP measurement only if:

• Patient falls into intermediate/moderate risk category (not low-risk, not already high-risk) 1
• Risk-based treatment decision remains uncertain after formal risk estimation 1
• Patient has unusual risk profile warranting refined assessment 1

Step 3: Interpret hs-CRP Results

• hs-CRP adds predictive value beyond lipids alone (P<0.001) 2
• hs-CRP remains predictive even in patients with LDL cholesterol <130 mg/dL 2
• Use hs-CRP to help reclassify intermediate-risk patients for treatment decisions 1

Important Limitations and Caveats

Quality of Evidence Concerns

• None of these novel markers have been evaluated as screening tests in randomized controlled trials with clinical events as outcomes 1
• Evidence relies on observational studies and meta-analyses, not intervention trials 1
• Publication bias exists, with smaller studies more likely to report higher relative risks 1

Specific Weaknesses of hs-CRP

• Multiple confounders: depends on other classical risk factors 1
• Narrow diagnostic window between normal and elevated levels 1
• Lacks specificity: similar risk elevation for non-cardiovascular inflammatory diseases 1
• No dose-effect relationship between changes in hs-CRP and CVD risk 1
• No specific therapies targeting CRP have shown reduction in CVD incidence 1
• Higher cost compared to traditional lipid testing 1

What NOT to Do

• Do not measure hs-CRP in low-risk asymptomatic individuals (adds no value) 1
• Do not measure hs-CRP in already high-risk patients (treatment decision already clear) 1
• Do not measure homocysteine for monitoring CVD prevention efforts 1
• Do not rely on novel biomarkers alone without assessing traditional risk factors first 1, 2

Practical Considerations

Cost-effectiveness context:

• Novel biomarkers were evaluated considering availability, cost, assay reliability, and downstream testing risks 1
• The ACC/AHA Work Group prioritized markers feasible for widespread use by primary care providers 1
• Higher cost of inflammatory markers compared to traditional lipid panels limits routine use 1

Emerging evidence:

• The 2013 ACC/AHA guidelines note that hs-CRP shows "some promise for clinical utility" but emphasize this is based on "limited data" 1
• The 2012 European guidelines similarly state that novel biomarkers have "only limited additional value" when added to standard risk assessment 1

Bottom line: Traditional lipid markers remain the foundation of cardiovascular risk assessment, with hs-CRP reserved for refining risk in intermediate-risk patients where treatment decisions remain uncertain after standard risk calculation 1, 2