When should you refer a patient with HIV for further cardiovascular workup? HIV/heart experts advise first figuring the pretest probability that a person has CHD.10 They suggest several tools for doing this (like the one in Table 3), cautioning that these formulas remain unvalidated in people with HIV.
|Table 3. Tool for Estimating Pretest Probability of Coronary Heart Disease|
|Variable||Score||Example: 52-Year-Old Woman|
|· Under 40/under 50||3|
|· 40 to 50/50 to 64||6||6|
|· 55 or older/65 or older||9|
|Estrogen status positive (F)||-3||-3|
|Estrogen status negative (F)||3|
|Angina history typical*||5|
|Angina history atypical||3|
|Angina history nonanginal||1||1|
|First-degree family history of coronary artery disease||1||1|
|Obesity (BMI >27 kg/m2)||1||1|
|Risk According to Total Score|
|Low: 0 to 8||Intermediate: 9 to 15||High: 16 or greater|
Source: Morise AP, Jalisi F. Evaluation of pretest and exercise test scores to assess all-cause mortality in unselected patients presenting for exercise testing with symptoms of suspected coronary artery disease. J Am Coll Cardiol. 2003;42:842-850.
* Diamond method.
In the Table 3 model, a score of 0 to 8 indicates low risk, 9 to 15 indicates intermediate risk, and 16 or higher signals high risk. People in the intermediate-risk stratum are the best candidates for a noninvasive stress test such as an exercise ECG, the HIV experts advise.10 People in the high-risk group often get false-negative results and thus are not great candidates for a noninvasive stress test. Instead, they should be referred for invasive coronary arteriography. People with a low-pretest probability of CHD tend to have false-positive test results, so they are not ideal candidates for noninvasive stress testing. Instead, they may be candidates for a stress test with nuclear perfusion imaging or wall motion imaging with echocardiography, but only if they have an intermediate global CHD risk or have a high-risk job, like flying airplanes.
This thoughtful review probes the ins and outs of noninvasive testing and cardiovascular markers, including high-sensitivity C-reactive protein (hsCRP), apolipoprotein (apo)B and apoA-1, carotid intimamedia thickness (cIMT), and coronary calcium scores.10 Although these markers see routine use in cohort studies and trials, their value in individual patients remains uncertain.
For the general population at least, hsCRP may have clinical value, according to a Centers for Disease Control and Prevention (CDC) panel -- but not for everyone who walks through the door.11 Instead, these experts suggest that hsCRP in people with a 10% to 20% CVD risk over 10 years may pick out those who would benefit from medical intervention, for example, with anti-lipid agents, anti-platelets, or cardioprotective drugs. (See note 11 for details of this panel's advice on clinical use of hsCRP in the general population.) But because hsCRP reflects inflammation, and because HIV-positive people have so many potential inflammation inciters (including HIV itself), the HIV/heart panel says "the role of hsCRP in clinical [HIV] practice is less clear" and suggests the need for hsCRP studies that control for traditional risk factors.10 One study published after this panel wrote did control for traditional risk factors when measuring the impact of CRP and HIV -- independently and together -- on acute myocardial infarction risk.12 In this analysis of 487 people with HIV and 69,870 HIV-negative people seen from January 1997 through December 2006, people with HIV and high CRP had 4-fold higher odds of an acute MI than HIV-negative people with normal CRP. (See Figure 13 in the first review article in this issue of RITA!)
In a 2010 issue of RITA!, HIV metabolics maven Steven Grinspoon, who headed this study in Boston's Partners HealthCare System, addressed the question of CRP use in the HIV clinic.13 "If you have a patient with a short duration of HIV and no other risk factors," he suggested, "measuring CRP early in the process is probably not useful. At the other end of the spectrum, in someone with severe dyslipidemia and diabetes, the additive value of CRP is probably irrelevant. But perhaps in borderline patients who have had chronic HIV for a long time and borderline dyslipidemia, much like the patients in this study,12 measuring CRP may be useful because having HIV and a high CRP would raise the MI risk 4-fold. I couldn't say specifically whether the predictive value of CRP in such patients is entirely independent of other markers. Our study would suggest this is the case, but further studies need to be done."13
Should HIV-positive men over 40 and women over 50 have an annual ECG, as EACS guidelines recommend?3 A 4518-person SMART study analysis lends credence to this advice,14 but some authorities voice reservations about routine ECGs. One in two people in the SMART analysis had a minor ECG abnormality, and 1 in 13 had a major abnormality. During a median follow-up of 28.7 months, 155 people (3.4%) got diagnosed with cardiovascular disease. A statistical model adjusted for study arm, demographics, cardiovascular risk factors, and HIV variables figured that a major ECG abnormality almost doubled the risk of a new cardiovascular diagnosis (hazard ratio 1.83, 95% confidence interval 1.12 to 2.97, P < 0.015), but major and minor abnormalities combined did not. The SMART investigators believe these findings "suggest that the ECG could provide a convenient risk-screening tool in HIV-infected patients."14
But in an interview in this issue, HIV/heart expert James Stein explains that screening ECGs are not recommended in the United States because they lack sensitivity in identifying cardiovascular disease and because they may yield false-positive results. ECGs, Stein believes, should be reserved for people with heart disease symptoms, like shortness of breath and chest discomfort.
|Relative Risk Category||Average hsCRP Level|
|Average||1.0 to 3.0 mg/L|
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