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Nearly 15 years ago researchers with the California-based health maintenance organization (HMO) Kaiser Permanente reported a signal of increased risk for heart attacks among HIV-positive people. In their latest report, the Kaiser researchers reveal a startling change: In recent years the risk for heart attack among HIV-positive people has declined to the same level as among HIV-negative people. We now explore their findings and reasons for this change.

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Study details

Researchers analysed information collected from medical charts of study participants between 1996 and 2011. Specifically, researchers used data from 24,768 HIV-positive people and compared them to data from HIV-negative people of similar age and gender. In total, data from 257,600 HIV-negative people were used. In general, HIV-positive people in the study were mostly male (91% men, 9% women) and were about 50 years old at the time of the most recent data analysis.

At the start of the study, researchers found that HIV-positive people were more likely to have certain cardiovascular and other disease risk factors, as follows:

Smoking

  • HIV-positive people – 45%
  • HIV-negative people – 31%

Drug use

  • HIV-positive people – 16%
  • HIV-negative people – 5%

Excessive alcohol use

  • HIV-positive people – 11%
  • HIV-negative people – 7%

Results—Heart attacks and trends

Among HIV-positive people there were a total of 320 heart attacks and among HIV-negative people there were 2,483 heart attacks.

Over the study period the researchers found that the risk for a heart attack gradually declined among HIV-positive people. In the initial study period (1996 to 1999), it was very high; by the final study period (2010 to 2011), heart attack risk had declined to the level seen among HIV-negative people, as follows:

  • 1996 to 1999 – a two-fold elevated risk
  • 2010 to 2011 – no increased risk

Differences in cardiovascular risk

Researchers focused on the years 2010 to 2011 and noted the following differences between HIV-positive and HIV-negative people:

Total cholesterol not elevated

  • HIV-positive people – 30%
  • HIV-negative people – 39%

Lower-than-normal levels of good cholesterol (HDL-C)

  • HIV-positive people – 39%
  • HIV-negative people – 26%

Higher-than-normal blood pressure (hypertension)

  • HIV-positive people – 29%
  • HIV-negative people – 36%

Smoking

  • HIV-positive people – nearly 50%
  • HIV-negative people – 34%

All of these differences between the two groups studied were statistically significant.

An interesting difference

In combing through medical records, researchers noticed a major difference between the study groups: HIV-positive people were more likely to be taking medications to help reduce their risk for cardiovascular disease, as follows:

Therapies for abnormal cholesterol levels

  • In the initial study period, only 6% of HIV-positive people were taking these drugs. However, in the final study period (2010 to 2011) the figure had increased to 32%.
  • Among HIV-negative people the equivalent figures were 4% and 24%.

Therapies to help normalize blood pressure

  • Initially, 17% of HIV-positive people were taking these medicines. By 2010 to 2011 the figure had increased to 35%.
  • Among HIV-negative people the equivalent figures were 14% and 31%.

Changes related to HIV therapy

Potent combination anti-HIV therapy is commonly called ART or HAART. In the early period of the study (1996 to 1999) 66% of participants were taking ART and 65% of ART users had their viral load fall below the 500-copies/ml threshold (at that time, this was considered “undetectable”). The average CD4+ count of HIV-positive people at that time was around 400 cells/mm3.

These figures contrast with the more recent period of the study (2010 to 2011), when 90% of participants were taking ART and 88% had a viral load less than 500 copies/ml. Furthermore, their average CD4+ cell count was slightly more than 600 cells/mm3.

Risk calculator

The Framingham Heart Study is a large American study that monitored HIV-negative people over many years to determine possible risk factors for cardiovascular disease (CVD). Based on the results of this study, risk calculators (sometimes called Framingham risk calculators that produce a Framingham risk score) have been developed to help doctors and nurses assess the risk of serious cardiovascular events occurring in their patients.

In the present California study, researchers found that in the period from 2010 to 2011, on average, HIV-positive people had a slightly lower Framingham risk score (9.5%) than HIV-negative people (10%).

Note that other research teams have found that the Framingham risk score likely under-estimates the cardiovascular risk faced by HIV-positive people. However, for the purposes of the overall argument made by the Kaiser team, let us accept what they have found with the Framingham risk score.

The main message

What the California study shows is that broad efforts aimed at improving overall health can reduce the risk for cardiovascular disease among HIV-positive people.

Screening is good

The Kaiser researchers note that when doctors who have registered with this HMO see patients, electronic notices appear in their computers reminding them to monitor their patients’ cholesterol, blood pressure and blood sugar levels. By screening their patients for these conditions and risks, doctors can intervene and improve patients’ overall health and reduce these risk factors for cardiovascular disease. The Kaiser medical computer system also prompts doctors to screen for smoking in their patients and encourages them to help their patients quit.

Other factors that could have made a difference

The research team also notes that since the Kaiser database issued one of the first reports from an observational study about increased risk for heart attacks among HIV-positive people nearly 15 years ago, it is likely that their healthcare providers may have been more aware of the need to reduce CVD risk factors.

Another factor that could have played a role in reducing the risk for CVD among HIV-positive people is the trend toward earlier initiation of ART. Emerging research suggests that people with untreated HIV infection and relatively low CD4+ cell counts may be at increased risk for accelerated CVD.

The California study has its limitations: It should have had more detailed information about smoking and substance use, including the use of so-called “club” or “party” drugs. However, an important finding from the Kaiser study is that many risks for CVD can be modified and that lowering these risks results in measureable benefits, including improved health and a reduced risk for heart attack.

Resources

—Sean R. Hosein

REFERENCES:

  1. Klein D, Hurley LB, Quesenberry CP, et al. Do protease inhibitors increase the risk for coronary heart disease in patients with HIV-1 infection? Journal of Acquired Immune Deficiency Syndromes. 2002 Aug 15;30(5):471-7.
  2. Klein DB, Leyden WA, Xu L, et al. Declining relative risk for myocardial infarction among HIV-positive compared with HIV-negative individuals with access to care. Clinical Infectious Diseases. 2015; in press.
  3. Silverberg MJ, Leyden WA, Xu L, et al. Immunodeficiency and risk of myocardial infarction among HIV-positive individuals with access to care. Journal of Acquired Immune Deficiency Syndromes. 2014 Feb 1;65(2):160-6.
  4. Srinivasa S, Fitch KV, Lo J, et al. Plaque burden in HIV-infected patients is associated with serum intestinal microbiota-generated trimethylamine. AIDS. 2015; in press.
  5. Petoumenos K, Reiss P, Ryom L, et al. Increased risk of cardiovascular disease (CVD) with age in HIV-positive men: a comparison of the D:A:D CVD risk equation and general population CVD risk equations. HIV Medicine. 2014 Nov;15(10):595-603.