Prevention of cardiovascular disease in people living with HIV

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The European AIDS Clinical Society (EACS) guidelines state that the intensity of efforts to prevent cardiovascular (CV) disease should depend on the underlying risk of its development, which can be estimated.1 
 


Routine assessments

Screening for CV disease in people living with HIV (PLWHIV) should be performed in men aged >40 years and women aged >50 years without CV disease.1 Routine assessments for CV disease include:


  • assessment of CV risk factors (see below for risk assessment tools) at HIV diagnosis, prior to starting combination antiretroviral (ARV) treatment and annually irrespective of ARV therapy1,2
  • screening for CV disease, using an electrocardiograph (ECG), at HIV diagnosis and annually irrespective of ARV therapy1
  • monitoring of blood pressure (BP) at HIV diagnosis, prior to starting ARV treatment and annually irrespective of ARV therapy1
  • monitoring for dyslipidemia at HIV diagnosis, prior to starting ARV treatment, after changing ARV therapy and at least annually1,2
    • a fasting lipid profile is required when considering medical intervention
    • more frequent monitoring may be indicated in the presence of persistent lipid elevation, CV risk factors or CV symptoms.2
       

Tools for estimating CV disease risk

  • Clinicians should assess PLWHIV for CV risk factors at least annually.1 The risk of developing CV disease can be estimated using various assessment tools:

  • the Framingham equation, to estimate the 5- and 10-year risk of CV disease using an algorithm based on the risk of myocardial infarction (MI) in the Data Collection on Adverse events of Anti-HIV Drugs (D:A:D) study3
    • the EACS guidelines recommend that the risk of developing CV disease in the next 10 years be estimated using the Framingham equation.1
       
  • Prospective Cardiovascular Münster Study (PROCAM) Risk Scores, to estimate the 10-year risk of developing a coronary event. Two scores are available:
  • the SCORE tool (part of the European guidelines on cardiovascular disease prevention in clinical practice4), which uses charts to estimate the 10-year risk of a first fatal atherosclerotic event
    • risk charts are for European populations and are intended for risk estimation in people who do not have a history of a relevant CV disease clinical event, diabetes or high levels of individual risk factors. 


Prevention of CVD1


Figure 1


i. Use the Framingham equation; a risk equation developed from HIV populations has been developed (see www.cphiv.dk/tools.aspx). This assessment and the associated considerations outlined in this figure should be repeated annually in all patients under care to ensure that the various interventions are initiated in a timely way.

ii. Options for ART modification include: (1) replace PI/r with NNRTI, RAL or by another PI/r known to cause less metabolic disturbances; (2) consider replacing d4T, ZDV or ABC with TDF or use a NRTI sparing regimen.

iii. Of the modifiable risk factors outlined, drug treatment is reserved for certain subgroups where benefits are considered to outweigh potential harm. Of note, there is a combined benefit of various interventions in target groups identified. Per 10 mmHg reduction in systolic blood pressure, per 1 mmol/L (39 mg/dL) reduction in TC and with use of acetylsalicylic acid, each reduces risk of IHD by 20-25 %; the effect is additive. Observational studies suggest that smoking cessation results in greatest reductions in risk of IHD-50 % – and this is additive to other interventions.

iv. See discussion on drug treatment of patients with lower CVD risk at www.nhlbi.nih.gov/guidelines/cholesterol/atp3_rpt.htm.

v. Target levels are to be used as guidance and are not definitive – expressed as mmol/L with mg/dL in parenthesis. In case LDL cannot be calculated because of high triglyceride levels, the non-HDL-c (TC minus HDL-c) target should be used which is 0.8 mmol/L (30 mg/dL) higher than the corresponding LDL-c target. Target levels for TG are not listed because an independent contribution from TG to CVD risk is uncertain and hence whether this condition should be treated.

vi. Evidence for benefit when used in persons without a history of CVD (including diabetics) is less compelling.



Reproduced with permission from the European AIDS Clinical Society Guidelines. Version 6.0.



Lifestyle interventions

  • Following calculation of the risk of CV disease, clinicians should advise patients on lifestyle interventions. The recommendations for lifestyle interventions in the EACS guidelines,1 which are based on those from the US Preventive Services Task Force,5 focus on:
    • smoking cessation
    • dietary counseling, including weight management and nutrition
    • promotion of exercise
       

Lifestyle modification for substance use may also be considered.2

Table 16 
 


Reproduced with permission from the European AIDS Clinical Society Guidelines Version 5.4. Prevention and Management of non-infectious comorbidities in HIV. 

 


ARV therapy modification

If an individual has a CV disease risk ≥20%, change of ARV therapy may be considered:1


  • a protease inhibitor (PI)/ritonavir (r) could be replaced with a NNRTI, RAL or with a different PI/r known to cause less metabolic disturbance
  • stavudine (d4T), zidovudine (ZDV) or abacavir (ABC) could be replaced with tenofovir (TDF) or an NRTI sparing regimen.


     

Treatment and targets for key modifiable risk factors


Key modifiable risk factors, such as blood pressure, coagulation, glucose and lipids, should be assessed. Drug treatment should be reserved for patients where benefits are considered to outweigh any potential risk.1  


Table 2

Risk factor Circumstances for drug treatment1 Recommended targets1
BP SBP ≥140 or DBP ≥90 mmHg 
(especially if 10-year CV disease risk ≥20%*) If diabetic/prior CV disease/CKD + 
proteinuria – SBP <130, DBP <80 
Others – SBP <140, DBP <90
Coagulation Established CVD or ≥50 years old and 
10-year CV disease risk ≥20%* Target not available, but consider treating 
with acetylsalicylic acid 75–150 mg, 
particularly those with a history of CV 
disease and those with diabetes mellitus
Glucose Confirm diabetes mellitus and treat with drugs HbA1c <6.5–7.0%

Lipids

 Established CV disease or type 2 diabetes mellitus or 10-year CV disease risk ≥20%*† 
Total cholesterol 
Optimal – ≤4 mmol/L (155 mg/dL)
Standard – ≤5 mmol/L (190 mg/dL)
LDL cholesterol
Optimal  – ≤2 mmol/L (80 mg/dL)
Standard  – ≤3 mmol/L (115 mg/dL)


*CV disease risk assessed using the Framingham equation. 


†For patients with a lower CV disease risk, the Third report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (ATP III Final Report) can be viewed for a discussion on drug treatment of abnormal lipid levels.7


LDL = low-density lipoprotein; SBP = systolic blood pressure; DBP = diastolic blood pressure; CKD = chronic kidney disease.



 

  • Some of the interventions have an additive effect:1

  • the risk of ischemic heart disease is reduced by 20–25% by the following, which have an additive effect:
    • each 10 mmHg reduction in systolic BP
    • each 1 mmol/L (39 mg/dL) decrease in total cholesterol
    • use of acetylsalicylic acid (aspirin).
       
  • observational studies suggest that smoking cessation reduces the risk of ischemic heart disease by 50%, which is additive to other interventions up to 5 years from when the intervention was first used.1
     

Table 3. Guidelines and reviews on preventing CVD

Organization Guidelines/reviews Information provided
For people living with HIV    
European AIDS Clinical Society1 EACS guidelines Section on preventing CV disease in people living with HIV.
New York State Department of Health AIDS Institute with John Hopkins University Division of Infectious Diseases2 Prevention of secondary disease: preventive medicine. Lipid screening and cardiovascular risk Recommendations on lipid screening and CV disease risk.
Department of Health and Human Services8 Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents
  • Do not specifically address CV disease prevention.

  • Sustained viral suppression and immune recovery may delay or prevent CV disease.
 
Early control of HIV replication with ARV therapy can be used as a strategy to reduce CV disease risk.

  • Incidence of CV disease increases with cumulative exposure to some NRTIs and protease inhibitors.

International AIDS Society-USA Panel9 Antiretroviral treatment of adult HIV infection. 2010 recommendations of the International AIDS Society-USA Panel
  • CV disease risk should be assessed by available tools.

  • Modifiable CV risk factors should be aggressively addressed in all people with HIV infection.
 
Abacavir, indinavir/r, lopinavir/r and fosamprenavir/r have been associated with an increased CV disease risk, so best avoided in patients with an already elevated CV disease risk.

American Heart Association10 Prevention Strategies for Cardiovascular Disease in HIV-Infected Patients Conference proceedings on management strategies for CV disease prevention in HIV patients

For the general population    
American College of Cardiology/American Heart Association11 American College of Cardiology/American Heart Association joint guidelines A wealth of guidelines on all aspects of CV disease prevention.
European Society of Cardiology4 European guidelines on cardiovascular disease prevention in clinical practice
  • A comprehensive guide to CV disease prevention in clinical practice.

  • Includes the SCORE tool that uses charts to estimate the 10-year risk of a first fatal atherosclerotic event.

  • Risk charts are for European populations.

NCEP ATP III12 National Institutes of Health. National Cholesterol Education Program. Expert panel on detection, evaluation, and treatment of high blood cholesterol in adults Provides detailed information on primary and secondary prevention.
World Health Organisation13 Guidelines for assessment and management of cardiovascular risk A comprehensive guide on reducing disability and premature deaths from CV disease in people at high risk who have not yet experienced a CV event.

US Preventive Services Task Force5 Guide to clinical preventive services 2010–2011 Includes recommendations on screening and assessment of heart and vascular diseases.


References

  1. European AIDS Clinical Society (EACS). Guidelines. Version 6.0. Accessed 3 July 2012.
  2. Office of the Medical Director, New York State Department of Health AIDS Institute in collaboration with the Johns Hopkins University Division of Infectious Diseases. Prevention of secondary disease: preventive medicine. Lipid screening and cardiovascular risk. Accessed 8 March 2011.
  3. Law M, Friis-Moller N, Weber R, et al. Modelling the three year risk of myocardial infarction among participants in the D:A:D study. HIV Med. 2003;4(1):1-10.
  4. Graham I, Atar D, Borch-Johnsen K, et al. European Guidelines on Cardiovascular Disease Prevention in Clinical Practice: Executive Summary: Fourth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (Constituted by representatives of nine societies and by invited experts). Eur Heart J. 2007 Oct;28(19):2375-2414.
  5. US Preventive Services Task Force. Guide to Clinical Preventive Services 2010–2011. Accessed 8 March 2011.
  6. European AIDS Clinical Society (EACS). Guidelines on Prevention and Management of Non-infectious Co-morbidities in HIV. Version 5-4. Accessed 22 June 2011.
  7. Third report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (ATP III Final Report). Accessed 8 March 2011.
  8. Department of Health and Human Services. Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents. Accessed 3 March 2011.
  9. Thompson MA, Aberg JA, Cahn P, et al. Antiretroviral treatment of adult HIV infection. 2010 recommendations of the International AIDS Society–USA PanelJAMA. 2010;304:321–333.
  10. Stein JH, Hadigan CM, Brown TT, et al. Prevention Strategies for Cardiovascular Disease in HIV-Infected Patients. Circulation. 2008;118:e54–e60.
  11. American College of Cardiology (ACC)/American Heart Association (AHA) joint guidelines. Accessed 6 April 2011.
  12. National Institutes of Health. National Cholesterol Education Program. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) (NCEP ATP III). Accessed 6 April 2011.
  13. World Health Organization. Prevention of cardiovascular disease. Guidelines for assessment and management of cardiovascular risk. Accessed 8 March 2011.