Table of Contents
HIV groups in the United States and Europe -- including pediatric experts -- have promulgated largely concordant guidelines on screening people with HIV infection for cardiovascular disease risk. These guidelines recommend some form of regular cardiovascular risk assessment for everyone with HIV infection. European guidelines call for annual screening including an ECG in men over 40 and women over 50, but US authorities do not recommend routine ECG screening. A National Heart, Lung, and Blood Institute panel considers pediatric HIV infection a moderate risk factor for accelerated atherosclerosis and recommends assessing cardiovascular risk factors in all children with HIV infection. The Framingham Risk Score overestimates or underestimates 10-year cardiovascular risk in some people with HIV, depending on individual risk factors and geographic origin. The DAD cardiovascular risk tool may offer a more precise gauge for populations like the DAD cohort. US HIV/heart experts suggest guidelines on when HIV patients need further noninvasive or invasive testing.
Guidelines for cardiovascular disease (CVD) screening in people with HIV are profuse yet elementary1-4 (Table 1). And pediatric solons have devised a transparent algorithm for sizing up cardiovascular risk in children with HIV5 (Table 2). But as with any facet of HIV medicine, the deeper you dig, the bigger the hole you can find yourself in. As the first two articles and the interview with James Stein in this issue make clear, cardiovascular risk with HIV infection is fraught with confounders ranging from parental chromosomes to pernicious lifestyle choices. Not to mention antiretroviral picks.
For adults, the HIV Medicine Association (HIVMA) and collaborating groups,1,2 the European AIDS Clinical Society (EACS),3 and the US Health Resources and Services Administration (HRSA)4 all recommend routine assessment of cardiovascular risk factors with a standard heart risk calculator when people enter care, start antiretroviral therapy (ART), switch antiretroviral regimens, and at regular intervals depending on calculated risk (Table 1). The EACS takes a more aggressive stance than the US groups, also calling for yearly electrocardiograms (ECGs) in men over 40 and women over 50.3 Lipids, blood pressure, and glucose also need regular checking (Table 1).
In 2011 an expert panel assembled by the National Heart, Lung, and Blood Institute (NHLBI) issued "Integrated guidelines for cardiovascular health and risk reduction in children and adolescents," which includes some HIV-specific screening advice (Table 2).5 The panel figures that HIV itself poses a moderate risk of accelerated atherosclerosis in children. Indeed, the Bogalusa Heart Study famously found that atherosclerotic changes can begin brewing in childhood.6 The NHLBI recommends assessing heart risk factors in children with HIV and -- in those with two or more risk factors -- taking steps to control weight, blood pressure, lipids, and glucose.
|Table 1. Screening Adults With HIV for Cardiovascular Disease Risk and Related Conditions|
|Cardiovascular disease||For every adult on ART, count CHD risk factors;† if 2 or more perform 10-year risk calculation‡1||For every adult risk assessment‡ before ART, then annually; for men over 40 and women over 50, ECG annually||For every adult, determine whether patient has established CHD or a CHD risk-equivalent state; if 2 or more risk factors, perform 10-year risk calculation‡|
|Lipids||For every adult, every 3 to 6 months, and consider 1 to 3 months after starting or modifying ART2||For every adult, fasting lipid profile at HIV diagnosis, before ART, then annually unless otherwise specifically indicated||For every adult, fasting lipid profile at baseline and when starting ART; within 3 to 6 months after starting ART and sooner for patients with abnormal values; then annually for patients with normal values and more often for patients with abnormal values|
|Hypertension||For every adult, blood pressure annually2||For every adult, blood pressure at HIV diagnosis, before ART, then annually unless specifically indicated||Assess when evaluating cardiovascular risk (above)|
|Diabetes||For every adult, fasting glucose every 6 to 12 months; consider 1 to 3 months after starting or modifying ART2||For every adult, fasting glucose at HIV diagnosis, before ART, then annually unless specifically indicated||For every adult, fasting glucose at baseline and within 3 to 6 months of starting or changing ART if baseline results normal; more often if abnormal|
ART, antiretroviral therapy; CHD; coronary heart disease; ECG, electrocardiogram; HIVMA, HIV Medicine Association.
* Recommendations of the HIV Medicine Association (HIVMA), Infectious Diseases Society of America, and Adult AIDS Clinical Trials Group.
† Risk factors are cigarette smoking, hypertension, low high-density lipoprotein (HDL) cholesterol, family history of premature coronary heart disease, and age older than 45 in men and 55 in women.
‡ Framingham 10-year risk calculator or DAD 5-year estimated risk calculator, both at www.cphiv.dk/tools.aspx.
|Table 2. Screening Children With HIV for Cardiovascular Disease5|
Children with HIV are considered as having moderate risk of accelerated atherosclerosis and early CVD*
Assess cardiovascular risk factors:
If 2 or more risk factors, consider child at high risk and establish following targets:
Use intensive lifestyle management plus condition-specific management. For details see source linked in footnotes.
CVD, cardiovascular disease; HbgA1C, hemoglobin A1C; HDL, high-density lipoprotein cholesterol; LDL, low-density lipoprotein cholesterol; TG, triglycerides.
Source: 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. 2011.5
Thanks to George K. Siberry, MD, MPH, Eunice Kennedy Shriver National Institutes of Child Health and Human Development, for help in identifying pediatric guideline sources.
* High-risk children include those with chronic kidney disease or diabetes type 1 or 2.
Is the Framingham score an accurate cardiovascular risk predictor for people with HIV? Studies that address this question agree that the Framingham risk-reckoner does a decent job in HIV-positive people but may underestimate 10-year risk in some subgroups and overestimate risk in others -- depending on risk factors and geographic origin. And no wonder. As the first two articles in this issue of RITA! make clear, people with HIV tote an ample burden of classic heart risk factors. On top of that they have a chronic inflammatory infection and may take cardiotoxic drugs to treat it. So compared with the general population, HIV-positive people face a more ramified array of risk mediators that may sway the prediction one way or the other.
The Framingham tool figures 10-year risk of "hard coronary artery disease," meaning myocardial infarction or coronary death, in adults without coronary heart disease, diabetes, or intermittent claudication (leg or arm pain caused by inadequate blood flow).7 It does so by assigning points for six variables: age, total cholesterol, HDL cholesterol, systolic blood pressure, anti-hypertensive therapy, and smoking status for men or women (Figure 1). A 10-year risk score below 10% indicates low risk, 10% to 20% signals intermediate risk, and 21% or higher signifies high risk. These 10-increment cut points are arbitrary.
Framingham and DAD cardiovascular disease risk calculators differ in their variables and output. The DAD calculator includes three general factors not featured in the Framingham tool (family history of coronary heart disease [CHD], previous smoking, and diabetes mellitus [DM]) and two HIV-specific factors (number of years taking indinavir (IDV) or lopinavir (LPV) and current indinavir, lopinavir, or abacavir).
An HIV-specific cardiovascular risk calculator engineered by the Data Collection on Adverse Events of Anti-HIV Drugs (DAD) Study leaves out anti-hypertensive therapy but adds five others factors to the equation -- number of years taking indinavir or lopinavir; current treatment with indinavir, lopinavir, or abacavir; previous smoking; diabetes; and family history of cardiovascular disease (Figure 1).8 Unlike Framingham, the DAD tool predicts 5-year risk of coronary heart disease (in people without a heart disease history). The DAD team considers a 5-year CHD risk below 1% low, 1% to 5% moderate, 5% to 10% high, and above 10% very high. The Framingham and DAD calculators are online at the links in references 7 and 8.
DAD researchers stress the big differences between their study group and the Framingham cohort.8 The HIV-negative US-based Framingham population included 2590 men and 2983 women from 30 to 74 years old followed for 12 years from a baseline date of 1968 to 1975. The DAD cohort was bigger (16,765 men and 5860 women), younger (median 40 years), and mostly European, and follow-up was shorter (4.8 years starting in the year 2000) than in Framingham. Everyone in DAD had HIV infection and most were taking antiretrovirals. The DAD investigators cite previous research indicating that the Framingham equation overpredicts cardiovascular disease risk in European populations. They note that the limited number of cardiovascular endpoints in DAD women prevented them from developing sex-specific prediction models.
How can these differences in variables and study populations affect risk calculations? Say your patient is a 52-year-old male smoker with a total cholesterol of 237, an HDL of 42, a systolic blood pressure of 138, and naive to anti-hypertensives. Feed those numbers into the Framingham brain and you come away with a 10-year risk of 20%, right at the cusp of high risk. That 20% means 20 of 100 people with this risk will have a heart attack in the next 10 years. Not happy odds.
Now you turn to the DAD decoder and add that this same patient took lopinavir for 3 years and is still taking lopinavir with abacavir. He's a current smoker, does not have diabetes, but has a family history of heart disease. Click the CALCULATE button. In the next 5 years, this man runs a 14.1% risk of coronary heart disease. But if he stopped lopinavir and is not on abacavir, this 5-year risk shrinks to 7.1%. If he quit smoking, the 5-year risk dwindles to 4.2%. If you take smoking out of the Framingham calculation detailed above, the 10-year risk falls to 9%. Thus, depending on the patient subgroup involved, the DAD tool would predict a greater or lesser coronary heart disease risk than Framingham.
In the study in which DAD investigators developed their risk calculator, it proved more accurate than the Framingham equation in estimating cardiovascular disease risk in the overall (largely European) cohort and in certain subgroups.8 In the DAD cohort, the Framingham model underpredicted risk compared with the DAD model when forecasting myocardial infarction or coronary heart disease in women, former smokers, and people with diabetes. On the other hand, Framingham overpredicted risk in people who never smoked.
"Although pending external validation," DAD collaborators note, "our models are intended for clinical usage to inform doctor-patient discussions on CVD risks and interventions,"8 as well as for research applications.
Before DAD investigators devised their risk calculator, they analyzed the accuracy of the Framingham formula in predicting myocardial infarction.9 Among European, US, and Australian DAD participants taking antiretrovirals, Framingham underpredicted actual MI incidence (9 observed MIs versus 5.5 predicted). But among antiretroviral-naive people, Framingham overpredicted actual incidence (3 observed MIs versus 7.6 predicted).
In an interview in this issue, cardiologist James Stein counsels that HIV clinicians should consider the Framingham model "as a starting point for discussion," recognizing that it's not perfect in people with HIV or people who differ from the young to middle-aged white US population in the Framingham cohort.
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