Smoking behavior of HIV-infected patients

doi:10.4236/health.2010.28135

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Vol.2, No.8, 913-918 (2010)

doi:10.4236/health.2010.28135

HEALTH

Openly accessible at

Smoking behavior of HIV-infected patients

Till Neumann1*, Nico Reinsch1, Stefan Esser2, Peter Krings1, Thomas Konorza1, Tanja

Woiwoid1, Michael Miller3, Norbert Brockmeyer4, Raimund Erbel1

1Department of Cardiovascular Medicine, Essen University, Medical School, Essen, Germany; *Corresponding Author:

till.neumann@uni-essen.de

2Department of HIV-Medicine & Dermatology, Medical School, Essen University, Essen, Germany

3Department of Gastroenterology, Medical School, Essen University, Essen, Germany

4Department of Dermatology, Medical School, Bochum University, Bochum, Germany

Received 10 March 2010; revised 2 April 2010; accepted 5 April 2010.

ABSTRACT

Recent reports describe an increased rate of

cardiovascular events in smoking HIV-infected

subjects. However, a lot is still unknown about

smoking in this patient population. The purpose

of the study was to analyze smoking behavior in

HIV-infected subjects as a risk factor of coro-

nary atherosclerosis and determine its effect on

the probability of coronary events. We analyzed

the cardiovascular risk factors of 294 HIV-infected

adults (age: 42.1  10.1 years; 77% males). An

elevated tobacco abuse was observed in 63.6%

of the HIV-infected patients. Tobacco use was

much more common in HIV-infected males than

in females (67.8% vs. 49.2%; p < 0.01). Even

elderly HIV-infected subjects had elevated rates

of pack-years, the daily tobacco consumption

does not seem to change at different ages (p >

0.2). Analysing the way of infection and the

status of smoking, patients with HIV-infection

acquired by heterosexual contact exhibited sig-

nificantly lower rates of smoking compared with

patients with HIV-infection acquired by MSM

(man having sex with man) or by intravenous

drug abuse (52.7% vs. 67.4%/82.1%, p < 0.01).

The effect of smoking on the 10yrs. probability

of coronary events determined by Framingham-

equation was superior compared with all other

classic cardiovascular risk factors. HIV-infected

patients exhibited an increased tobacco use.

Knowledge about smoking behavior in this pa-

tient population is essential to evaluate the risk

of cardiovascular events and to implicate pre-

vention strategies for HIV-infected subjects.

Keywords: Human Immunodeficiency Virus;

Atherosclerosis; Smoking; Tobacco Consumption

1. INTRODUCTION

Since the development of effective antiretroviral therapy

concepts, the replication of the human immunodefi-

ciency virus (HIV) could be decreased and its coincident

deleterious effects on the immune system be diminished.

Therefore, the HIV-infection has become a chronic dis-

ease with a potential for long-term survival.

However, the spectrum of HIV-related diseases has

shifted from opportunistic infections towards long-term

complications of HIV-infection and the antiretroviral

therapy. Based on an increased rate of coronary events in

HIV-infected patients, a variety of investigators are cur-

rently focusing on metabolic disorders as a long-term

effect of the highly antiretroviral therapy (HAART) and

their risk for premature atherosclerosis [1,2]. In particu-

lar, a rising number of case reports on myocardial infarc-

tion in HIV-infected patients in recent years implicated

an association between HAART and coronary heart dis-

ease [3-8]. However, the results of register analyses of

coronary heart disease in HIV-infected patients, which

display a correlation between an increased rate of car-

diovascular events and antiretroviral therapy, are still

controversially discussed [9,10].

Therefore, in HIV-infected subjects further patho-

physiological mechanisms may participate to premature

atherosclerosis. In particular, classic cardiovascular risk

factors, including smoking, are suspected to play a rele-

vant role in the development coronary events. The pre-

sent study was performed to assess smoking behavior as

a cardiovascular risk factors in HIV-infected subjects

and to determine its effects on the probability of coro-

nary heart disease.

2. METHODS

Patient population: All HIV-infected patients being

T. Neumann et al. / HEALTH 2 (2010) 913-918

914

treated in the Internal Medicine HIV-out patient depart-

ment over a time period of 5 years were included into

analysis. Of these 294 HIV-infected patients one hun-

dred seventy three (58.9%) acquired HIV-infection by

homosexual contact of man having sex with man, 83

(28.2%) by heterosexual contact, 28 (9.5%) by intrave-

nous drug abuse and 10 (3.4%) by blood transfusion.

A medical history was taken and a physical examina-

tion performed by a physician. Of each patient, demo-

graphic data, state of infection, antiretroviral medication

and cardiovascular risk factors including personal history,

lipid disorders, and smoking behaviors were analysed. If

subjects were smokers, further information including the

amount of cigarettes per day as well as the frequency

and the time period of smoking－resulting in pack years

data －were recorded and analysed. Resting systolic

blood pressure (SBP) and diastolic blood pressure (DBP)

were measured by oscillometric sphygmo-manometry.

A total of 28 patients (9%) were on lipid-lowering

therapy. Of these patients the lipid values were included

before the start of the lipid-lowering therapy. The study

was in agreement with the Local Council on Human

Research and the Declaration of Helsinki.

Calculation of the probability of coronary events:

The prediction of coronary events was determined by the

Framingham algorithm [11]. As major cardiovascular

risk factors age, gender, total cholesterol, LDL choles-

terol, blood pressure, smoking and diabetes were fea-

tured into the calculation. The result of the Framingham

prediction algorithm determines the 10-year probability

of coronary events and gives information about the im-

pact of each cardiovascular risk factor.

Statistical Analysis: Variables that described demo-

graphic data and data of smoking behavior were ex-

pressed as mean values  SD. The comparison of these

variables was performed between distinct groups by

one-way ANOVA and Bonferroni test. Nominal vari-

ables were expressed as frequencies and comparisons

performed by using Fishers exact test. Skewed variables

such as variables describing the probability of coronary

events were expressed as median and comparisons were

done by Wilcoxon rank sum test and Dunn´s test (indis-

tinct groups were compared by Wilcoxon signed rank for

paired observations adjusted according to Bonferroni-

Holm). A p < 0.05 was considered significant.

3. RESULTS

Overall, HIV-infected patients exhibited an increased

tobacco use. Of all 294 HIV-infected patients in the pre-

sent study, 187 (63.6%) were regular smokers, nearly all

of them consuming cigarettes (only one patient smoked

pipe). The demographic data of smokers and non-

smokers are presented in Table 1. There were no sig-

nificant differences between smoking and non-smoking

HIV-infected subjects concerning age, height, weight or

body mass index in our analyses. Moreover, there was

no significant difference in HIV-RNA concentration,

CD4-count and antiretroviral therapy.

In both groups, about one third of patients were in

stage A, B and C of the disease, without significant dif-

ferences due to the rate of smoking (smokers: 31.7%/

33.3%/35.0%; non-smokers: 33.7%/26.9%/39.4%, res-

pectively). Further cardiovascular risk factors, including

systolic and diastolic blood pressure and elevated lipid

or glucose concentration did not differ significantly be-

tween the two groups (Table 2).

Tobacco use was much more common in HIV-infected

males than in females. While more than two thirds of

HIV-infected males were smokers, the smoking rate in

HIV-infected females was less than 50 percent (67.8% vs.

49.2%; p = 0.008). Even gender differences in HIV-

infected patients were particularly assessed concerning

the rate of smoking, no significant difference were pre-

sent between these two groups in the time interval of

smoking and the amount of cigarettes consumed includ-

ing pack-years and cigarettes per day). Only 2.0% of

HIV-infected males and 3.0% of females showed a daily

cigarette consumption that was less than 5 cigarettes. In

contrast, 44.1% of males and 33.4% of females smoked

each day more than 20 cigarettes (Table 3).

Table 1. Demographics and Antiretroviral Therapy.

Non-Smoker Smoker p-value

Demographics

N (male/female)107 (73/34) 187 (154/33)

Age [y] 42.9  11.6 41.7  10.9 0.38

Height [cm] 174.0  9.9 175.7  8.3 0.11

Weight [kg] 70.6  11.6 70.313.5 0.84

BMI [kg/m²] 23.4  3.7 22.7  3.7 0.11

HIV-RNA

[copies/ml]

(50, 7000)

200

(50, 10500) 0.22

CD4 [cells/µl] 438  247 466  304 0.42

Antiretroviral

Therapy

NRTIs 91 (85.0%) 160 (85.6%)1.00

NNRTIs 48 (44.9%) 69 (36.9%) 0.22

PIs 49 (45.8%) 89 (47.6%) 0.81

Demographics data are presented as mean values  SD, Antiretroviral

therapy in percentage; NRTIs: nucleosidal reverse transcriptase inhibi-

tors; NNRTIs: non-nucleoside reverse transcriptase inhibitors; PIs:

protease inhibitors

T. Neumann et al. / HEALTH 2 (2010) 913-918

915

Table 2. Cardiovascular Risk Factors.

Non-SmokerSmoker p-value

Hypertension

SBP [mmHg] 122.8  17.3120.3  16.5 0.23

DBP [mmHg] 79.6  11.3 78.2  11.6 0.33

Hyperlipidaemia

Total cholesterol

[mmol/L] 5.59  1.47 5.49  1.40 0.56

HDL-cholesterol

[mmol/L] 1.20  0.49 1.14  0.45 0.34

LDL-cholesterol

[mmol/L] 3.52  1.69 3.50  1.38 0.93

Triglycerides

[mmol/L] 2.88  2.96 2.76  3.19 0.76

Hyperglycemia

Glucose

[mmol/L] 5.5 (4.9, 6.3)5.3 (5.0, 6.3) 0.53

HbA1c [%] 5.3  0.9 5.1  1.1 0.10

Data are mean values  SD or median (lower quartile, upper quartile);

SBP: systolic blood pressure; DBP: diastolic blood pressure.

The majority of smoking HIV-infected were 31 to 40

years old and consumed 11 to 40 cigarettes per day. No

significant differences were found in our study between

the rate of smoking at different ages (18-30 yrs: 58.4%,

31-40 yrs: 64.6%, 41-50 yrs. 69.8%, > 50 yrs. 55.3%).

As expected, elderly HIV-infected subjects of more than

40 years had a significantly higher amount of pack-years

compared with younger HIV-infected subjects. Even the

smoking period of elderly subjects was increased, no

significant differences were found in respect of daily

tobacco consumption (Table 4).

Analysing the way of infection and the status of smo-

king, also significant differences were present (Table 5).

In particular, the group of patients with HIV-infection

acquired by heterosexual contact exhibited significantly

lower rates of smoking compared with patients with

HIV-infection acquired by MSM (man having sex with

man) or by intravenous drug abuse. The lowest rate of

smoking was present in patients with HIV-infection ac-

quired by blood transfusion. However, a no significant

differences to other groups were found due to the low

rate of patients of this way of infection.

As presented in Figure 1, the prediction value for

coronary events in the next 10 years was significantly

higher in smoking HIV-infected patients compared with

non-smoking HIV-infected patients (7.2% vs. 4.9%; p <

0.001), respectively. Especially, male HIV-infected pa-

tients exhibited an elevated probability of coronary

events compared with female HIV-infected patients in

the smoker group (9.8% vs. 2.3%; p < 0.001), respec-

tively. The calculated effect on the probability of coro-

Table 3. Gender differences.

Mean  SD < 5 5-10 11-20 21-40 > 40

Cigarettes per day:

- all 25.0  14.0 2.1% 15.5% 40.1% 35.3% 7.0%

- males 25.2  13.5 2.0% 14.3% 39.6% 37.0% 7.1%

- females 24.0  16.4 3.0% 21.2% 42.4% 27.3% 6.1%

p-value (males vs. females): 0.68

Pack years:

all 21.9  15.2 6.4% 20.3% 30.5% 36.4% 6.4%

males 22.6  14.8 5.9% 18.8% 29.2% 39.6% 6.5%

females 19.1  17.0 9.1% 27.3% 36.4% 21.2% 6.0%

p-value (males vs. females): 0.24

Table 4. Age differences.

N (%)

Mean  SD < 5 5-10 11-20 21-40 > 40

Cigarettes per day:

- 18-30 22 (11.8%) 19.4  8.4 9.1% 13.6% 54.6% 22.7% 0.0%

- 31-40 81 (43.3%) 24.7  12.5 1.2% 14.8% 38.3% 38.3% 7.4%

- 41-50 50 (26.7%) 26.5  15.5 0.0% 18.0% 34.0% 42.0% 6.0%

- > 50 34 (18.2%) 26.9  17.3 2.9% 14.7% 44.1% 26.5% 11.8%

p-value between groups: 0.31

T. Neumann et al. / HEALTH 2 (2010) 913-918

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Table 5. Way of Infection.

All Group 1 Group 2 Group 3 Group 4

Smoking, % 63.6% 66.4% 53.0% 85.7% 40.0%

package-years 21.4  1.0 22.5  1.4 25.2  2.5 24.7  2.6 38.8  14.6

cigarettes per day 24.8  1.0 24.9  1.4 20.1  2.3 20.2  2.1 44.2  16.0

Group 1: HIV-infection acquired by man having sex with man; Group 2: HIV-infection acquired by heterosexual contact; Group 3: HIV-infection

acquired by intravenous drug abuse; Group 4: HIV-infection acquired by blood transfusion.

Figure 1. The 10-year probability of coronary events deter-

mined by the Framingham prediction algorithm in distinct

groups of HIV-infected individuals, due to the quality of

smoking. The 10-year probability of coronary heart disease in

the next 10-years was significantly higher in smokers than in

non-smokers. Data are expressed as median plus lower quartile

and upper quartile.

nary events by smoking is superior compared with all

other classic cardiovascular risk factors.

4. DISCUSSION

The present study demonstrates that smoking is a com-

mon cardiovascular risk factor in HIV-infected patients.

Furthermore, smoking seems to have a remarkable and

superior impact for the occurrence of cardiovascular

events in this patient population compared with other

classic cardiovascular risk factors including hyperlipi-

daemia.

Recent clinical trials describe an increased rate of car-

diovascular events in HIV-infected patients [9,10]. In

addition, the rate of atherosclerosis in autopsies of

HIV-infected patients has increased [12]. Consequently,

there is an increased concern that these changes may

lead to an epidemic increase of cardiovascular diseases

in the HIV-positive population.

The development of new antiretroviral drugs includ-

ing protease inhibitors has reduced the mortality and

morbidity of HIV-infected patients [13]. The increased

lifespan in combination with the metabolic side effects

of the highly active antiretroviral therapy (HAART),

such as hyperlipidaemia and insulin resistance, has been

expected to contribute to the increased rate of athero-

sclerosis in HIV-infected patients. However, other risk

factors than hyperlipidaemia and insulin resistance, may

also have an effect on the development of premature

atherosclerosis in HIV-infected patients [14-16].

The results of the present study emphasise, that smo-

king is an important risk factors, which has a remarkable

impact on the incidence of cardiovascular events in HIV-

infected patients. Our data further reveal a high percent-

age of smokers among the study population of individu-

als living with HIV. The rate of smokers in our sample

was far above the prevalence estimated for the general

adult population in the same area (63.6% vs. 23.5%, p <

0.001) [17]. In addition to the increased rate of smoking,

the cigarette consume per day of HIV-infected smokers

was elevated compared with HIV-negative smokers in

the general adult population (25.0 vs. 16.4 cigarettes per

day). One reason for the higher frequency of smokers

might be the portion of people with intravenous drug

abuse and men who have sex with men in the population

of HIV-infected patients. Both groups have an increased

smoking rate [18,19].

Among individuals living with HIV, previous studies

have found that smokers are at greater risk for develop-

ing bacterial pneumonia, oral lesions, and the acquired

immune deficiency syndrome. However, our study re-

sults reveal that smokers with HIV-infection also have

an elevated risk of cardiovascular events than non-

smokers with HIV-infection. The risk of cardiovascular

events was especially elevated in male smokers with

HIV-infection. However, the probability of cardiovascu-

lar events of female smokers with HIV-infection was

comparable or even lower than the risk of non-smoking

HIV-infected individuals.

Compared with HIV-infected non-smokers, the in-

creased probability of cardiovascular events in HIV-

infected smokers was not associated to differences in

other coronary risk factors, such as hypertension, hyper-

lipidaemia or hyperglycaemia. Furthermore, there were

no differences in antiretroviral therapy between the

smoker group and the non-smoker group.

T. Neumann et al. / HEALTH 2 (2010) 913-918

917

Openly accessible at

As a limitation of the present study, the probability of

cardiovascular events for the next ten years was deter-

mined by an algorithm. This Framingham algorithm had

been used previously to determine the risk of cardiovas-

cular events in HIV-infected patients and the algorithm

considered the traditional cardiovascular risk factor such

as age, gender, lipid values, blood pressure, smoking,

and hyperglycaemia [11,20]. Nevertheless, this type of

calculation has limitations. In particular, it is only an

estimation of cardiovascular events and does not present

the de facto event rate. However, it is the only way to

receive an opinion about the impact of cardiovascular

risk factors in this patient population. Hence, it is a rele-

vant tool to compare the impact of different risk factors

in a specific patient population.

The results of the present study give insides in smok-

ing behaviour. These information about smoking behav-

ior are essential to evaluate the risk of cardiovascular

events and to implicate prevention strategies for HIV-

infected subjects. The reduction of cardiovascular risk

factors should become a routine prevention in the care of

HIV-infected patients, which now have an increased

lifespan due to highly active antiretroviral therapy.

5. ACKNOWLEDGEMENTS

This work was supported by the Competence Network of Heart Failure

(Kompetenznetz Herzinsuffizienz) funded by the Federal Ministery of

Education and Research (BMBF), FKZ 01GI0205. Our work was not

supported by any form of sponsorship or has any affiliations that might

lead to bias or conflict of interest.

REFERENCES

[1] Depairon, M., Chessex, S., Sudre, P., et al. (2001) Pre-

mature atherosclerosis in HIV-infected individuals－

focus on protease inhibitor therapy. AIDS, 15(3),329-334.

[2] Duong, M., Buisson, M., Cottin, Y., et al. (2001) Coro-

nary heart disease associated with the use of human im-

munodeficiency virus (HIV)-1 protease inhibitors: Re-

port of four cases and review. Clinical Cardiology,

24(10), 690-694.

[3] Behrens, G., Schmidt, H., Meyer, D., Stoll, M. and

Schmidt, R.E. (1998) Vascular complications associated

with use of protease inhibitors. Lancet, 351(9120), 1958.

[4] Eriksson, U., Opravil, M., Amann, F.W. and Schaffner, A.

(1998) Is treatment with ritonavirus a risk factor for

myocardial infarction in HIV-infected patients? AIDS,

12(15), 2079-2080.

[5] Flynn, T.E. and Bricker, L.A. (1999) Myocardial infarc-

tion in HIV-infected men receiving protease inhibitors.

Annals of Internal Medicine, 131(7), 548.

[6] Gallet, B., Pulick, M., Genet, P., Chedin, P. and Hiltgen,

M. (1998) Vascular complications associated with use of

protease inhibitors. Lancet, 351(9120), 1958-1959.

[7] Henry, K., Melroe, H., Huebesch, J., Hermundson, J.,

Levine, C., Swensen, L. and Daley, J. (1998) Severe

premature coronary artery disease with protease inhibi-

tors. Lancet, 351(9112), 1328.

[8] Vittecoq, D., Escaut, L. and Monsuez, J.J. (1998) Vascu-

lar complications associated with use of HIV protease

inhibitors. Lancet, 351(9120), 1959.

[9] Klein, D., Hurley, L., Quesenberry, C.P. Jr, Sidney, S.

(2002) Do protease inhibitors increase the risk for coro-

nary heart disease in patients with HIV-1 infection?

Journal of Acquired Immune Deficiency Syndromes,

15(5), 471-477.

[10] Sabin, C.A., Worm, S.W., Weber, R., Reiss, P., El-Sadr,

W., Dabis, F., De Wit, S., Law, M., D'Arminio Monforte,

A., Friis-Møller, N., Kirk, O., Pradier, C., Weller, I., Phil-

lips, A.N. and Lundgren, J.D. (D:A:D Study Group)

(2008) Use of nucleoside reverse transcriptase inhibitors

and risk of myocardial infarction in HIV-infected patients

enrolled in the D:A:D study: A multi-cohort collaboration.

Lancet, 371(9635), 1417-1426.

[11] Wilson, P.W.F., D'Agostino, R.B., Levy, D., Belanger,

A.M., Silbershatz, H. and Kannel, W.B. (1998). Predic-

tion of coronary heart disease using risk factor categories.

Circulation, 97(18), 1837-1847.

[12] Morgello, S., Mahboob, R., Jakoushina, T., Khan, S. and

Hague, K. (2002). Autopsy findings in a human immu-

nodeficiency virus-infected population over 2 decades.

Archives of Pathology & Laboratory Medicine, 126(2),

182- 90.

[13] Palella, F.J., Jr, Delaney, K.M., Moorman, A.C., et al.

(1998) Declining morbidity and mortality among patients

with advanced human immunodeficiency virus infection.

HIV Outpatient Study Investigators. New England Jour-

nal of Medicine, 338(13),853-860.

[14] Neumann, T., Woiwod, T., Neumann, A., Miller, M.,

Ross, B., Volbracht, L., Brockmeyer, N., Gerken, G. and

Erbel, R. (2003). Cardiovascular risk factors and probabil-

ity of cardiovascular events in HIV-infected patients: Part I:

Differences due to the acquisition of HIV-infection. Euro-

pean Journal of Medical Research, 8(6), 229-235.

[15] Neumann, T., Woiwod, T., Neumann, A., Miller, M.,

Ross, B., Volbracht, L., Brockmeyer, N., Gerken, G. and

Erbel, R. (2004) Cardiovascular risk factors and prob-

ability of cardiovascular events in HIV-infected patients:

Part II: Gender Differences. European Journal of Medi-

cal Research, 9(2), 55-60.

[16] Neumann, T., Woiwod, T., Neumann, A., Miller, M.,

Ross, B., Volbracht, L., Brockmeyer, N., Gerken, G. and

Erbel, R. (2004) Cardiovascular risk factors and prob-

ability of cardiovascular events in HIV-infected patients:

Part III: Age Differences. European Journal of Medical

Research, 9(5), 267-272.

[17] Federal Statistical Office (2008) Every fourth person

aged 15 or over smokes regularly. Sustainable Develop-

ment in Germany. Verlag Metzler Poeschel, Stuttgart, 44.

[18] Clarke, J.G., Stein, M.D., McGarry, K.A. and Gogineni, A.

(2001) Interest in smoking cessation among injection drug

users. American Journal on Addiction, 10(2), 159-166.

T. Neumann et al. / HEALTH 2 (2010) 913-918

918

[19] Stall, R.D., Greenwood, G.L., Acree, M., Paul, J. and

Coates, T.J. (1999) Cigarette smoking among gay and

bisexual men. American Journal of Public Health, 89(12),

1875-1878.

[20] Hadigan, C., Meigs, J.B., Wilson, P.W., et al. (2003)

Prediction of coronary heart disease risk in HIV-infected

patients with fat redistribution. Clinical Infectious Dis-

eases, 36(7), 909-916.