People living with HIV who smoke have an almost three-fold greater risk of heart attack than HIV-negative smokers, according to Danish data published online ahead of print in Clinical Infectious Diseases. The study suggests that smoking drives the larger number of heart attacks observed in people living with HIV in resource-rich settings, with other factors being less important.
At the same time, a major provider of healthcare in California has reported a declining incidence of heart attacks in people living with HIV in recent years, with rates now equivalent to HIV-negative people. They attribute the change not just to smoking cessation, but also to better monitoring of cardiovascular risks, greater use of statins and earlier initiation of antiretroviral therapy.
Cardiovascular disease and heart attacks
In an era of effective antiretroviral therapy, the focus of medical care for many people living with HIV has shifted towards the management of comorbidities and health conditions that are associated with ageing, such as cardiovascular disease.
Several observational studies have reported a 1.5 to 2 fold increased risk of heart attack (myocardial infarction) among people living with HIV, compared to people who do not have HIV. Around one-in-ten deaths of people living with HIV are due to heart attacks and other cardiovascular disease.
The underlying causes of this are the subject of scientific debate. Having HIV directly causes chronic inflammation and changes to cholesterol and other lipids which may accelerate cardiovascular disease. Some research suggests that specific antiretroviral drugs may contribute to these processes. Genetic factors, accelerated ageing in people with HIV and high blood pressure have all also been proposed as potential factors.
But behavioural and social factors are also likely to be part of the explanation. Most importantly, rates of smoking tend to be considerably higher in people with HIV than in the general population. In addition, differences in socio-economic status, ethnicity, alcohol consumption and recreational drug use have been observed between cohorts of HIV-positive and HIV-negative people. While researchers attempt to measure factors such as these and take them into account when comparing the risk of heart attack in HIV-positive and HIV-negative people, this process is inevitably inexact and incomplete.
A higher risk for smokers in Denmark
In order to better understand the links between HIV infection, smoking and the risk of heart attack, Line Rasmussen and colleagues compared data on 3,251 HIV-positive patients living in Denmark and 13,004 individuals from the general population in Copenhagen, matched for age and gender.
Specifically, the researchers wanted to find out whether smoking has a higher impact on the risk of heart attack among smokers living with HIV than among HIV-negative smokers. They also aimed to estimate to what extent smoking can explain the increased risk of heart attack among people living with HIV.
Data were collected between 1995 and 2013. People who had ever injected drugs were excluded from the analysis.
Rates of smoking were much higher among people living with HIV:
- 47% currently smoked, compared to 19% in the general population.
- 19% were ex-smokers, compared to 34% in the general population.
- 34% had never smoked, compared to 46% in the general population.
The proportion of people with HIV experiencing a heart attack (2.9%) was considerably higher than in the general population (1.0%).
The researchers analysed the risk of heart attack according to whether a person smoked:
- Current smokers living with HIV had an almost three-fold increased risk of heart attack, compared to smokers in the general population of the same age and gender: incident rate ratio 2.83 (95% confidence interval 1.71 – 4.70).
- Ex-smokers living with HIV had an almost two-fold increased risk: incident rate ratio 1.78 (95% confidence interval 0.75 – 4.24).
But people living with HIV who had never smoked had no greater risk of heart attack than non-smokers in the general population of the same age and gender: incident risk ratio 1.01.
The latter finding has not been observed in other studies, which have typically found that people with HIV have a raised risk of heart attack, even if they don’t smoke.
The data were analysed in another way, looking only at people living with HIV and taking individuals who had never smoked as the comparison group. Current smokers had a statistically significant six-fold greater risk of heart attack (incident risk ratio 6.06) and ex-smokers had over double the risk (incident risk ratio 2.64).
The Danish data therefore suggest that the principle reason for the increased rate of heart attack in people with HIV is smoking. Not only is smoking more prevalent in this group, it may also have a greater physiological impact than in people who do not have HIV.
The researchers estimate that 72% of heart attacks in people living with HIV were attributable to smoking – considerably higher than the estimated 24% in the general population. If current smokers living with HIV could give up smoking and have the risk of ex-smokers, the total number of heart attacks in people with HIV would be cut by 42%.
Discussing the research in a linked commentary, M. John Gill and Dominque Costagliola question whether quite as many heart attacks are caused by smoking as this. They suspect that some of the social and behavioural differences in the study participants may not have been fully captured by the research. Moreover they believe that lipid abnormalities, chronic inflammation and the choice of antiretrovirals may also contribute to cardiovascular disease.
Nonetheless, they say it is quite clear that smoking remains the dominant cause of heart attacks in people living with HIV. The study should encourage clinicians to prioritise their work on smoking cessation.
“Seizing every opportunity during HIV care delivery to focus our efforts to reduce the high rate of tobacco smoking offers the greatest potential for reducing MI [myocardial infarction] rates,” they say. “Encouragement and support for our patients in their efforts to stop smoking offers immense health benefits.”
Fewer heart attacks in California
Published at the same time in Clinical Infectious Diseases is a report from the Kaiser Permanente managed healthcare programme, which provides care to six million Californians. As previously reported by Aidsmap, whereas the risk of heart attack for their HIV-positive members was double that of HIV-negative members in 1996-99 (risk ratio 1.8, 95% confidence interval 1.3 – 2.6) it has been steadily declining since then. In 2010-2011, there was no increased risk of heart attack for members living with HIV (risk ratio 1.0, 95% confidence interval 0.7 – 1.4).
The data come from a comparison of 24,768 individuals living with HIV and 257,600 individuals who do not have HIV, with data collected from 1996 to 2011.
In recent years, the mean Framingham risk score for cardiovascular disease has been slightly lower for members with HIV than for members without HIV, with better results for some risk factors (such as total cholesterol) but poorer results for some others (such as high blood pressure). Whereas 45% of people living with HIV had ever smoked, 31% of HIV-negative people had done so.
Moreover there has been a dramatic increase in the use of statins and other lipid-lowering drugs by HIV-positive patients during the period of study – from 5.5 to 31.5%.
“In our large integrated care setting of insured patients, these results may be explained by access to care, and broadly disseminated CVD [cardiovascular disease] risk reduction efforts, such as the implementation of health prompts that appear during all clinic visit registrations, including reminders for cholesterol and blood pressure monitoring, diabetes follow-up, and smoking cessation,” the researchers write.
An additional explanation offered by the researchers is the transformation in the use of antiretroviral therapy in people living with HIV since 1996. Drugs which have fewer associations with cardiovascular disease are now more likely to be used. Furthermore, patients start treatment earlier and have higher CD4 cell counts, avoiding the immunodeficiency which is associated with chronic inflammation and cardiovascular disease.
“Our findings lend support to the concept that increased MI [myocardial infarction] risk for HIV patients is largely reversible with continued emphasis on primary prevention in combination with early initiation of ART to preserve immune function,” the authors conclude.
Rasmussen LD et al. Myocardial infarction among Danish HIV-infected individuals: Population attributable fractions associated with smoking. Clinical Infectious Diseases, 2015.
Gill MJ & Costagliola D. Myocardial Infarction in HIV infected persons: Time to focus on the silent elephant in the room? Clinical Infectious Diseases, 2015.
Klein DB et al. Declining Relative Risk for Myocardial Infarction Among HIV-Positive Compared with HIV-Negative Individuals with Access to Care. Clinical Infectious Diseases, 2015.