Keywords
Introduction
The utilization of internet cardiovascular risk calculators (i.e., pooled cohort equations) has been useful since their introduction over a decade ago. However, more recent clinical investigations have demonstrated their loss of accurate predictive ten-year risk in several large populations including obesity
1
, young men2
, asymptomatic women3
, and different ethnic groups4
. The efforts to improve mathematical calculations by the American Heart Association, the Framingham Study, the Reynolds equations and others, have been met with confusion for patients and healthcare professionals because of their differing input variables and output recommendations5
. Their inherent limitations leading to inaccurate predictions include risk assessment at only one point in time and their inability to accurately input more or less (i.e., intermittent) exposure to major risk factors over the lifetime of the individual.Risk Parameters
New investigations into cardiovascular pathophysiology have demonstrated that all major risks can be expressed by at least one of the following blood tests: 1) lipid profile, 2) Apolipoprotein B (Apo B), 3) Apolipoprotein (a) (Lp[a]), and 4) high sensitivity C-reactive protein (hsCRP). Because atherosclerosis is a chronic disease developing over the lifetime of the individual starting in infancy, an abnormality in any of these variables requires follow-up evaluation independent of that already necessitated by traditional clinical risk factors.
The prevalence of cardiovascular disease is increasing. Prevention of heart attacks and strokes requires identification of all individuals with an increased risk profile, and subsequent preventive therapy when indicated. The knowledge of the atherosclerotic plaque burden can support the clinical justification for introducing improved lifestyle and pharmacological therapy. This approach avoids introducing unnecessary therapeutic interventions or frequent evaluations if no vessel atherosclerotic plaque is present.
Traditional risk calculator equations can be superseded by assessment of proven clinical risk factors and measurement of their mediators. In place of the traditional risk equations, the physician should identify a patient's family history of atherosclerosis, the past or current presence of hypertension, smoking, and diabetes, and order the four baseline blood tests listed above to assess cardiovascular risk. If any of these parameters are abnormal, then a coronary artery calcium scan (CAC scan) should be obtained if the patient's age is appropriate for subclinical atherosclerosis. Coronary artery calcium scanning has permitted the reclassification of individuals evaluated by a risk equation score (e.g., Framingham risk score) throughout the risk categories ranging from 12% to 15% in the low-risk category, 52% to 66% in the intermediate-risk category, and 34% to 36% in the high-risk category
6
. In a recent change in policy, the American Heart Association now supports calcium scanning in most individuals with proven risk factors7
. Furthermore, coronary artery calcium heart scanning has become widely available at relatively minimal cost. Preventive treatment is not only inexpensive and safe but is effective in the clinical population8
.Informative blood testing
(table 1) A lipid profile provides the following useful risk information – a total cholesterol, an HDL cholesterol, a triglyceride level, and a calculated LDL cholesterol. An HDL cholesterol concentration assesses the reverse cholesterol transport capability of the individual; a triglyceride level assesses the risk of elevated triglycerides (cardiovascular and pancreatitis), and an LDL cholesterol assesses the potential atherosclerotic hazard of this lipoprotein remnant to atherosclerotic plaque formation. In addition, a non-HDL cholesterol level can be calculated from these lipids to provide an estimate of the total quantity of cholesterol contained in atherogenic particles.
Table 1Important Risk Parameters to be Assessed to Categorize CVD Risk
| Test | Normal Value | Key Points | What is assessed | Approximate Quest Cost | Limitations |
|---|---|---|---|---|---|
| Lp (a) Ref # 9 | <30 mg/dl | Genetically determined. Not decreased by statins | A specific atherosclerotic particle that inhibits plasminogen | $50 | Normal range is lab assay specific |
| Apo B Ref # 10 | <90 mg/dl | Provides an accurate number of atherosclerotic particles | Identifies # of small LDL particles for improved risk assessment | $35 | None |
| hsCRP Ref # 12 | <1.0 mg/L | Assesses the degree of systemic inflammation (specify “high sensitivity”) | Measures low values of CRP Major risk for coronary artery atherosclerosis | $79 | Also Increased during acute illness |
| LDL chol Ref # 8,10 | < 70 mg/dl Lower is desirable | Accounts for 80% of total cholesterol in plasma | Usually calculated but if TG direct assay available | $156 for entire lipid panel | Does not include all atherogenic particles |
| CAC scan Ref # 6, 7,13,14 | Zero (No calcified plaques) | Excellent noninvasive predictor of future CVD risk | Highly correlated with atherosclerotic plaque burden | $50 - $200 Widely available | Identifies only calcified plaques |
Measuring Lp(a) provides an assessment of a very important independent risk factor
9
. Lp(a) is genetically determined and minimally changes over the lifetime of the individual. It tends to be elevated in certain ethnic groups such as African Americans. Not only does it contain an atherogenic LDL particle but it also contains amino acid kringles (amino acid folds held together by disulfide bonds) that share homology with kringles on plasminogen. Their interaction results in an inhibition of thrombolysis and an increased risk of a coronary thrombosis. Lp(a) is highly susceptible to oxidation, making it available to macrophages that initiate atherosclerotic plaque formation. At autopsy, Lp(a) has been identified in atherosclerotic plaques. It has the undesirable properties of being proatherosclerotic, proinflammatory, and prothrombotic.Apolipoprotein B (Apo B) is a constituent of all atherogenic particles. Since there is only one Apo B per particle, its quantification provides a precise assessment of the number of total atherogenic particles. This is important since many studies have shown that small, dense LDL cholesterol particles are more atherogenic than large LDL particles, even with the same total cholesterol particle content
10
. Non HDL cholesterol does not provide this important information, since it only measures total particle cholesterol content. Recent data suggest that apo B must be reduced to reduce cardiovascular disease11
.HsCRP is a surrogate marker for the severity of systemic inflammation
12
. Inflammation is a critical component of the atherosclerotic process. It damages the arterial endothelium and thereby permits additional LDL cholesterol particles to enter the subendothelial space. It also stimulates the endothelial secretion of specific cytokines (e.g., VCAM-1) that increase the adherence of monocytes to the arterial wall. These monocytes then pass through the endothelium by diapedisis, internalize the oxidized LDL-cholesterol particle, and form fatty streaks, the precursor to atherosclerotic plaques.Recent studies now demonstrate the value of atherosclerotic plaque burden as quantified by the coronary artery calcium scan's ten-year cardiovascular event prediction
13
. The quantity of calcium is an excellent predictor of total atherosclerotic plaque. Alternatively, a zero calcium score provides assurance of protection from an atherosclerotic event for at least five years. A coronary calcium scan is noninvasive, requires approximately 10 minutes, and costs approximately $100. Guidelines for the appropriate use of CAC scanning have been published14
.Summary
In contrast to placing a patient in a specific risk category by risk equations, (e.g., low, intermediate, high, very high), just two categories are necessary: 1) very low risk and 2) significant potential risk. This categorization is easily determined from the assessment of the above evaluation. If all above measurements are within a normal range with no hypertension, smoking, diabetes, nor family history of atherosclerosis, then cardiovascular risk is minimal. However, if any of the tests are abnormal, then a coronary artery calcium scan should be obtained after considering the age of the individual and the severity of the risk factor. Treatment should be individualized for each patient. Identifying individuals at risk, documenting early coronary atherosclerosis, and treating them aggressively will reduce the number one cause of death in the U.S., i.e., atherosclerotic cardiovascular disease
8
.Financial Support
The authors received no external funding support for this manuscript.
Declaration of Competing Interest
All authors had access to the data and a role in writing the manuscript.
Acknowledgements
none
References
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