A 45-year-old male physician presented for an opinion on how to manage his premature CAD and wishes to know what he could do to prevent a further cardiovascular event. He is a lifetime nonsmoker with no hypertension or hyperlipidemia, but with a significant family history of CAD in his father, who died in his 40s secondary to a myocardial infarction. The patient had developed angina two years prior, while carrying his luggage in the airport. An initial nuclear stress test failed to demonstrate any ischemia; he was treated medically and remained asymptomatic for some time. The following year his anginal symptoms escalated significantly to where he would have angina with minimal exertion. He underwent a CT coronary angiogram which demonstrated significant proximal LAD disease. He had a cardiac catheterization subsequently confirming severe, 1-vessel CAD of the proximal LAD which was successfully treated with PCI and implantation of a zotarolimus drug-eluting stent. Since then, he has had no further chest discomfort, angina, or dyspnea and continues to exercise regularly. He currently takes ASA 81 mg daily, atorvastatin 20 mg daily, lisinopril 2.5 mg daily, and niaspan 500 mg daily. He currently exercises routinely 30 minutes daily and is following a Mediterranean diet. He measures his blood pressure at home and routinely runs in the 130 mmHg systolic range. On exam, his current blood pressure is 127/78 mmHg, and his exam is otherwise unremarkable. An ECG demonstrated sinus bradycardia at 52 bpm andwas otherwise normal. An echocardiogram demonstrated a left ventricular ejection fraction of 65% with no regional wall motion abnormalities. C-reactive protein was measured at 1 mg/L, and a prior assay of Lp(a) measured it at 47. His total cholesterol measured 88 with an LDL of 33, HDL of 43, and triglycerides of 60.
For this patient with established but stable CAD who is otherwise asymptomatic, which is the correct statement regarding his risk of a subsequent acute coronary syndrome (ACS)?
The correct answer is: D. Multimarker scores result in only small increases in the ability to classify risk in comparison to conventional risk factors
A. CRP levels in this patient are within the normal values and thus are not predictive of increased event rate. hsCRP has been shown to add to risk prediction above standard risk factor assessment. Even though hsCRP can identify an increased risk for an ACS event independent of LDL cholesterol, the magnitude of this effect is only marginal in subjects free of known CAD. In the WHI study, the CRP level did not significantly improve CHD prediction either alone or in combination with other biomarkers. Moreover, hsCRP is a nonspecific marker of systemic inflammation, and as such by itself, has low predictive accuracy for acute cardiac events in individual patients. For CRP individually in the study by Eapen et al., a CRP level > 3.0 mg/L demonstrate a hazard ratio of 1.26 for combined endpoint of all-cause death, MI, or revascularization.
B. High levels of lipoprotein(a) [Lp(a)] are known to be a cardiovascular risk factor associated with premature coronary artery disease. Lipoprotein(a) has an additional prognostic value over the GRACE risk score in predicting one-year adverse outcomes in NSTE-ACS. The combination of serum Lp(a) with GRACE risk score could provide enhanced risk stratification in patients with ACS. CAD patients with a history of ACS have higher Lp(a) plasma levels and a significantly higher proportion of low molecular weight apolipoprotein(a) isoforms compared with patients with stable angina and controls.
C. NT-proBNP, and BNP levels have been shown to be important prognostic markers and independent predictors of adverse events in patients presenting with STEMI, and ACS including NSTEMI. However, there is minimal data to suggest that elevations in these levels are predictive of future myocardial infarction.
D. Elevation of various individual biomarkers such as high-sensitivity C-reactive protein (hs-CRP), brain natriuretic peptide (BNP), CK-MB, troponin, and D-dimer, in patients presenting with acute coronary syndromes have been shown to further stratify these population's risk of subsequent adverse events. Individually, the predictive power of each biomarker is modest.
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