27 January 2015 

Danish study underscores link between heart attacks and smoking

Data from several observational studies have suggested that the increased risk for heart attacks among HIV-positive people may arise from the use of specific anti-HIV drugs or whole classes of such drugs. However, observational studies, no matter how large, can never provide definitive answers to research questions. In 2006, the results of a robustly designed clinical trial called SMART found that continuous potent combination anti-HIV therapy (commonly called ART or HAART) resulted in a reduced risk of death and a reduced risk for heart attacks compared to interrupting ART.

Commenting on these and other studies, Line Rasmussen, MD, PhD (Odense University Hospital, Denmark), stated that “the mechanisms that drive the association between HIV and the risk of [heart attack] seem to rely on complex associations of known and unknown factors.” At least that seemed to be the case until now.

The massive impact of smoking

In general, smoking tobacco is one of the greatest risk factors for cardiovascular disease and heart attacks among HIV-negative people. As surveys have found that HIV-positive people tend to have higher rates of smoking (usually two to three times greater than among HIV-negative people), it is highly likely that smoking is a major contributor to poor health, including heart attacks, and reduced quality of life among HIV-positive people.

In 2013 a Danish study with HIV-positive people found that smoking was linked to at least a four-fold increased risk of death and a more than five-fold increased risk of dying from causes unrelated to HIV. The same study found that among ART users smoking has a more significant impact on decreasing life expectancy than HIV.

Smoking and heart attacks

Spurred by these findings, Danish researchers have performed additional analyses of their data to understand the cardiovascular impact of smoking in HIV-positive people.

They found that among HIV-positive people who never smoked there was no increased risk for heart attack compared to HIV-negative people who never smoked. However, among HIV-positive people who currently smoke, the risk of a heart attack was about three-fold greater than among HIV-negative smokers. The Danish researchers estimated that if the HIV-positive people in their study were to quit smoking, then at least 40% of heart attacks could be prevented. Resources for quitting smoking appear at the end of this CATIE News bulletin.

Study details

The Danish researchers created a study called the Danish HIV Cohort, which has enrolled several thousand HIV-positive people and monitored their health for many years. The study team compared data collected from 3,251 HIV-positive participants and 13,004 HIV-negative people. Data from each HIV-positive person was compared with data from four HIV-negative people of similar age and gender.

It is important to note that none of the participants injected street drugs (we will discuss this point later).

Denmark has many high-quality databases that the study team accessed to confirm reports of heart attacks, hospitalizations and deaths that occurred. The researchers focused on the time period between 1st January 1999 and 1st April 2013.


Researchers classified participants as smokers if they disclosed that they smoked tobacco at least once weekly. Researchers subdivided participants into different smoking categories, as follows:


  • never smoked – 34%
  • previously smoked – 19%
  • current smokers – 47%


  • never smoked – 46%
  • previously smoked – 34%
  • current smokers – 20%

The average profile of the HIV-positive participants when they entered the study was as follows:

  • age – 45 years
  • 79% men, 21% women


Over the course of the study, heart attacks occurred and were distributed by HIV status as follows:

  • HIV-positive people – 3% had a heart attack
  • HIV-negative people – 1% had a heart attack

Based on the above results alone, it would seem that HIV infection greatly increases the risk of a heart attack. However, the Danish researchers then took into account tobacco smoking—something that other data sets and observational studies have not always done.

The distribution of heart attack risk among HIV-positive people (compared to HIV-negative people) is as follows:

  • never smoked – no increased risk
  • previously smoked – approximately a two-fold increased risk of a heart attack
  • current smokers – approximately a three-fold increased risk of a heart attack

The role of smoking and quitting

Overall, researchers found that in HIV-positive people who were classed as “ever smokers” by the Danish team (this category includes both current and previous smokers), smoking played a role in 72% of heart attacks.

In contrast, among HIV-negative people, smoking played a role in 24% of heart attacks.

Researchers estimated that if HIV-positive current smokers in the study could quit smoking, more than 40% of heart attacks in this population “could potentially be prevented.”

People who use street drugs

The Danish researchers stated: “As almost all HIV-infected individuals with a history of [injecting street drugs] were smokers and differ considerably according to risk-taking behaviour and prevalence of co-morbidities, these individuals were excluded [from the present analysis] to avoid confounding.”

This statement underscores the poor health prospects of people who inject street drugs. Furthermore, the statement points to the need for health and social service agencies to engage with people who use street drugs (injected or taken in other ways) so that their addiction treatment and mental and emotional health needs can be assessed and addressed. In this way, people who use street drugs can get help to stabilize their health, eventually recover from addiction (including nicotine addiction) and ultimately reap the full survival benefits of ART.

Credit due

The Danish researchers should be congratulated for uncovering a clear link between smoking and heart attacks among HIV-positive people. Their findings can be used to strengthen smoking cessation programs and related research.

Key points

  • HIV-positive people were twice as likely as HIV-negative people to smoke. This finding is interesting and requires further research so that scientists and doctors can gain insight into the reasons for the greater prevalence of smoking. Hopefully such insight can assist smoking prevention and cessation programs for HIV-positive people.
  • HIV-positive people who did not smoke had no increased risk of a heart attack compared to HIV-negative non-smokers.
  • HIV-positive people who smoked had a three-fold increased risk of a heart attack compared to HIV-negative people who smoked.
  • The research team estimated that smoking played a role in nearly 75% of heart attacks that occurred among HIV-positive people.
  • The researchers also estimated that if all HIV-positive participants in the study who currently smoked were to quit, at least 40% of heart attacks could be prevented.
  • Studies need to take smoking into account when conducting analyses of cardiovascular risk in people with HIV.


Sean R. Hosein


  1. Gill MJ, Costagliola D. Myocardial infarction in HIV-infected persons: Time to focus on the silent elephant in the room? Clinical Infectious Diseases. 2015; in press.
  2. Rasmussen LD, Helleberg M, May M, et al. Myocardial infarction among Danish HIV-infected individuals: Population attributable fractions associated with smoking. Clinical Infectious Diseases. 2015; in press.
  3. Lohse N, Hansen AB, Pedersen G, et al. Survival of persons with and without HIV infection in Denmark, 1995-2005. Annals of Internal Medicine. 2007 Jan 16;146(2):87-95.
  4. Samji H, Cescon A, Hogg RS, et al. Closing the gap: increases in life expectancy among treated HIV-positive individuals in the United States and Canada. PLoS One. 2013 Dec 18;8(12):e81355.
  5. May MT, Gompels M, Delpech V, et al. Impact on life expectancy of HIV-1 positive individuals of CD4+ cell count and viral load response to antiretroviral therapy. AIDS. 2014 May 15;28(8):1193-202.
  6. Lohse N, Gerstoft J, Kronborg G, et al. Comorbidity acquired before HIV diagnosis and mortality in persons infected and uninfected with HIV: a Danish population-based cohort study. Journal of Acquired Immune Deficiency Syndromes. 2011 Aug 1;57(4):334-9.