When and How to Screen for Cardiovascular Disease Risk in People With HIV

Summer 2013

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Which Patients Need Deeper Probing?

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
VariableScoreExample: 52-Year-Old Woman
Age (male/female):  
· Under 40/under 503 
· 40 to 50/50 to 6466
· 55 or older/65 or older9 
Estrogen status positive (F)-3-3
Estrogen status negative (F)3 
Angina history typical*5 
Angina history atypical3 
Angina history nonanginal11
Smoking (any)1 
First-degree family history of coronary artery disease11
Obesity (BMI >27 kg/m2)11
 Total Score9
Risk According to Total Score
Low: 0 to 8Intermediate: 9 to 15High: 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.

* Thanks to Nina Friis-Møller, MD, PhD, DMSc, Copenhagen HIV Programme, University of Copenhagen, for reviewing this section of this article.

References and Notes

  1. Dubé MP, Stein JH, Aberg JA, et al. Guidelines for the evaluation and management of dyslipidemia in human immunodeficiency virus (HIV)-infected adults receiving antiretroviral therapy: recommendations of the HIV Medicine Association of the Infectious Disease Society of America and the Adult AIDS Clinical Trials Group. Clin Infect Dis. 2003;37: 613-627.
  2. Aberg JA, Kaplan JE, Libman H, et al. Primary care guidelines for the management of persons infected with human immunodeficiency virus: 2009 update by the HIV Medicine Association of the Infectious Diseases Society of America. Clin Infect Dis. 2009;49:651-681.
  3. Lundgren JD, Battegay M, Behrens G, et al. European AIDS Clinical Society (EACS) guidelines on the prevention and management of metabolic diseases in HIV. HIV Med. 2008;9:72-81.
  4. US Department of Health and Human Services Health Resources and Services Administration HIV/AIDS Bureau. Guide for HIV/AIDS clinical care. January 2011.
  5. Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents. Integrated guidelines for cardiovascular health and risk reduction in children and adolescents. The report of the expert panel. 2011.
  6. Berenson GS, Srinivasan SR, Bao W, et al. Association between multiple cardiovascular risk factors and atherosclerosis in children and young adults. The Bogalusa Heart Study. N Engl J Med. 1998;338:1650-1656.
  7. Framingham Heart Study. Hard coronary heart disease (10-year risk).
  8. Friis-Møller N, Thiébaut R, Reiss P, et al; for the DAD study group: Predicting the risk of cardiovascular disease in HIV-infected patients: the Data Collection on Adverse Effects of Anti-HIV Drugs Study. Eur J Cardiovasc Prev Rehabil. 2010;17:491-501.
  9. Law MG, Friis-Møller N, El-Sadr WM, et al. The use of the Framingham equation to predict myocardial infarctions in HIV-infected patients: comparison with observed events in the D:A:D Study. HIV Med. 2006;7:218-230.
  10. Hsue PY, Squires K, Bolger AF, et al. Screening and assessment of coronary heart disease in HIV-infected patients. Circulation. 2008;118:e41-e47.
  11. Pearson TA, Mensah GA, Alexander RW, et al. Markers of inflammation and cardiovascular disease: application to clinical and public health practice: a statement for healthcare professionals from the Centers for Disease Control and Prevention and the American Heart Association. Circulation. 2003;107:499-511. This panel makes the following points about clinical use of hsCRP in the general population:
    1. Of current inflammatory markers identified, hsCRP has the analyte and assay characteristics most conducive to use in practice. (Class IIa, Level of Evidence B)
    2. Measurement of hsCRP is an independent marker of risk and, in those judged at intermediate risk by global risk assessment (10 to 20% risk of CHD per 10 years), at the discretion of the physician, may help direct further evaluation and therapy in the primary prevention of CVD. The benefits of such therapy based on this strategy remain uncertain. (Class IIa, Level of Evidence B)
    3. Patients with persistently unexplained, marked elevation of hsCRP (>10mg/L) after repeated testing should be evaluated for noncardiovascular etiologies. (Class IIa, Level of Evidence B)
    4. In patients with stable coronary disease or acute coronary syndromes, hsCRP measurement may be useful as an independent marker of prognosis for recurrent events, including death, MI, and restenosis after PCI. The benefits of therapy based on this strategy remain uncertain. (Class IIa, Level of Evidence B)
    5. Measurement of markers should be done twice (averaging results), optimally two weeks apart, fasting or nonfasting in metabolically stable patients. If hsCRP level is >10 mg/L, test should be repeated and patient examined for sources of infection or inflammation. (Class IIa, Level of Evidence B)
    6. hsCRP levels, using standardized assays, categorize patients as follows:

      Relative Risk CategoryAverage hsCRP Level
      Low<1 mg/L
      Average1.0 to 3.0 mg/L
      High>3.0 mg/L

  12. Triant VA, Meigs JB, Grinspoon SK. Association of C-reactive protein and HIV infection with acute myocardial infarction. J Acquir Immune Defic Syndr. 2009;51:268-273.
  13. Hidden heart disease and other non-AIDS risks in HIV patients. An interview with Steven Grinspoon, MD. Research Initiative, Treatment Action! 2010;15:5-12.
  14. Soliman EZ, Prineas RJ, Roediger MP, et al. Prevalence and prognostic significance of ECG abnormalities in HIV-infected patients: results from the Strategies for Management of Antiretroviral Therapy study. J Electrocardiol. 2011;44:779-785.
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This article was provided by The Center for AIDS Information & Advocacy. It is a part of the publication Research Initiative/Treatment Action!. Visit CFA's website to find out more about their activities and publications.

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