At a Glance

Biochemical markers of lipid status and/or inflammation can provide data useful in assessing the risk of cardiovascular disease in patients who may have conventional markers of increased cardiovascular risk, such as cigarette smoking, elevated blood pressure, and diabetes mellitus, but are currently asymptomatic and have no history of coronary heart disease. They may also prove useful when patients are overweight (obese), physically inactive, have a family history of coronary heart disease (CHD), or exhibit signs of insulin resistance.

Several global risk score calculations that are based on a combination of history and physical and biochemical measures are available. Global risk scores are particularly valuable in patients who are asymptomatic with no clinical history of CHD.

What Tests Should I Request to improve the estimate of future risk of cardiovascular disease? In addition, what follow-up tests might be useful?

The biochemical tests you need to utilize global risk scoring would be based on the score you wish to utilize:

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Framingham Score: requires Total and HDL Cholesterol levels, along with age, gender, smoking status, and blood pressure.

The Reynolds Score: requires hs-CRP, total and HDL cholesterol, along with age, gender, parental history, smoking status, and blood pressure. In women with diabetes, the HbA1c is used to further enhance the calculation.

PROCAM Score: uses LDL and HDL cholesterol and triglycerides, along with family history, smoking status, age, and diabetes status. This score is validated in men only.

SCORE (Systematic Coronary Risk Evaluation): utilizes Total and HDL cholesterol, along with age, gender, smoking status, and blood pressure

Measurement of CRP can be useful in the selection of patients for statin therapy, if the patient is male, 50 years of age or older, or female, 60 years of age or older, with low-density lipoprotein cholesterol less than 130 mg/dL; not on lipid-lowering, hormone replacement, or immunosuppressant therapy; without clinical CHD, diabetes, chronic kidney disease, severe inflammatory conditions, or contraindications to statins.

Global scores can be biased based on the populations studied and not applicable to some demographic groups. Patients from countries other than the United States can be assessed against the World Health Organization (WHO) guidelines that include data based on various regions of the world. (Table 1)

Table 1
C-reactive protein C-reactive protein C-reactive protein C-reactive protein
<1 mg/L 1.0-3.0 mg/L 3.1-10 mg/L >10 mg/L
Lower relative cardiovascular risk Average relative cardiovascular risk Higer relative cardiovascular risk Persistent levels associated with infection or inflammation, not useful in predicting cardiovascular risk

Are There Any Factors That Might Affect the Lab Results? In particular, does your patient take any medications – OTC drugs or Herbals – that might affect the lab results?

C-reactive protein (high sensitivity test)

Patients with existing acute inflammatory processes will have CRP levels exceeding 3.0 mg/L.

Repeat testing within 2 weeks is recommended to exclude benign transient elevations in CRP associated with infection or inflammation.

Levels are affected by adiposity, smoking, and hormone replacement therapy. However, it is the level of persistent inflammatory processes, independent of cause, that is thought to increase future risk of cardiovascular events.

The use of a high-sensitivity CRP assay (hs-CRP) is required if the data is used in cardiovascular risk assessment. Assays not designed for high-sensitivity analysis are not suitable.

Lipid profiles

Samples collected after fasting are preferred to avoid lipemia that may interfere with the assay. Nonfasting samples are acceptable.

However, the Friedwald equation for calculation of LDL-cholesterol is invalid when triglyceride levels exceed 400 mg/dL, which can occur from chylomicrons present in the blood after meals.

What Lab Results Are Absolutely Confirmatory?

There are no laboratory results that are absolutely confirmatory for future cardiovascular events. The biomarkers available provide an estimate of the risk of future events.

What Follow-up Tests Might Be Useful?

Homocysteine, Lipoprotein(a), and fibrinogen may provide additional useful information in particular groups of patients but lack substantial clinical data for use in most asymptomatic populations.

The 2010 American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines do not recommend use of lipoproteins, apolipoproteins, neither particle size nor density, naturietic peptides, or genomic testing to assess asymptomatic individuals.

Patients with existing hypertension, smokers, diabetics, or those with chronic renal disease or an elevated homocysteine may indicate higher risk of CHD.

Increased fibrinogen levels may indicate higher risk of CHD in patients with a prior history of smoking, hypertension, increased LDL-Cholesterol, and increased lipoprotein(a).

The lack of standardized assays for fibrinogen and lipoprotein(a) complicate their use in CHD risk prediction. Immunoassays for fibrinogen appear to provide better predictive data than assays based on clotting time (functional assays).