Identifying HIV patients with an unfavorable cardiovascular risk profile in the clinical practice: Results from the SIMONE study

doi:10.1016/j.jinf.2008.03.007

Journal of Infection

Volume 57, Issue 1, July 2008, Pages 33-40

https://doi.org/10.1016/j.jinf.2008.03.007 Get rights and content

Summary

Objective

To identify and characterize HIV-infected patients at higher cardiovascular risk in ordinary clinical settings.

Design

Multicenter, nationwide cross-sectional study.

Methods

Consecutive HIV-patients, attending scheduled visits at facilities involved in the Italian coordination group for the study of allergies and HIV infection (CISAI), were included between February and April, 2005. Their 10-year probability of acute coronary events was calculated using the Framingham Risk Score (FRS) as well as 3 other cardiovascular algorithms (“PROCAM”, “PROGETTO CUORE”, “SCORE”); Metabolic Syndrome (MS) was diagnosed according to the National Cholesterol Education Program definitions. An estimated 10-year CVD ≥10% and/or MS led to the diagnosis of high CV risk. We compared selected clinical features between high- and low-risk patients.

Results

A total of 1230 HIV infected patients (72% males, mean age of 43 ± 9 years), 185 of whom treatment-naïve, were evaluated. FRS gave the highest estimate of CV risk. The mean 10-year risk for acute coronary events according to FRS was 7.4 ± 7.0. MS was present in 22% of the observed patients. Accordingly, 443 patients (36%) were classified at high risk. Twelve percent of the patients (n = 142) had both a FRS ≥10% and a diagnosis of MS. The main single predictor of increased cardiovascular risk was smoking (60% of whole sample). A higher prevalence of clinically evident lipodystrophy and a higher CD4 T-cell counts were found both in patients with higher FRS and in patients with high FRS and MS (both p < 0.001).

Conclusions

The worst estimation of CV risk was obtained with the FRS algorithm. Clinical evidence of lipodystrophy and higher CD4 T-cell counts were closely associated to a worse cardiovascular risk profile.

Introduction

Atherosclerotic cardiovascular disease (CVD), a leading cause of morbidity and mortality in the general population, is of an increasing concern also for HIV-infected patients. Although a high level of cardiovascular morbidity was reported for HIV infected patients in the pre-CART (Combination AntiRetroviral Therapy) era,¹ this issue became even more relevant since CART extended their life span.2, 3 Accordingly, estimates of coronary heart disease (CHD) risk are now felt as a valuable tool for clinical practice. The Framingham risk score (FRS) provides an estimate of CVD risk validated in the general North American population4, 5, 6 and is widely considered as a reference method.⁷ Furthermore, an increased prevalence of Metabolic Syndrome (MS) has been reported in HIV infected patients.8, 9, 10 The main pathogenic mechanism associated with MS in HIV patients is reckoned to be CART induced insulin-resistance,¹¹ and its frequent identification in patients on CART has brought the issue to the forefront. The diagnosis of MS may help identifying HIV patients at high risk of developing both type 2 diabetes and CVD.12, 13 The SIMONE (SIndrome Metabolica ONE) study was accordingly designed to get a cross-sectional estimate of both prevalence and characteristics of MS in an unselected population of Italian HIV infected patients, employing the National Education Cholesterol Program (NCEP) criteria,¹⁴ and to evaluate the global probability for CVD in these patients.

Although the estimation of CHD risk might prove useful both to establish the relative contribution of different risk factors and for clinical management in HIV patients, estimates of CHD risk from long term observational studies are still scanty in these settings,15, 16 and estimates of CVD using algorithms other than FRS are lacking.17, 18

In this study, we performed a cross-sectional, comparative evaluation of CHD risks using the FRS,⁵ the PROCAM score,¹⁹ the Italian “Progetto CUORE” algorithm²⁰ and the SCORE algorithm,²¹ using data collected for the SIMONE study. We aimed to identify an easy-to-use procedure to screen HIV infected patients at higher cardiovascular (CV) risk in ordinary clinical settings, possibly incorporating data on MS prevalence.

Section snippets

Patients and study design

The SIMONE study design has been described elsewhere.²² Briefly, it was a cross-sectional survey started in February and completed in April, 2005. It was conducted by the CISAI group (Coordinamento Italiano per lo Studio Allergia e Infezione da HIV – Italian coordination group for the study of allergies and HIV infection). Within this period, all patients attending scheduled or unscheduled visits at hospitals participating the CISAI group were eligible. Using a standard data collection form,

Results

A total of 1243 HIV infected patients were enrolled. Five men aged more than 75 and 8 patients with missing variables for MS diagnosis or FRS calculation were excluded. Analyses were performed on 1230 subjects (71.5% males), including 185 (15.1%) treatment-naïve subjects. Patients' mean age was 43.0 ± 8.8 years. Table 2 sets out their main characteristics and the results of 10-year estimated cardiovascular risk, applying the 4 different mentioned algorithms. The prevalence of patients with

Discussion

The SIMONE study reported on a large multicentric, unselected population of Italian HIV-infected patients, mostly on CART, observed in routine clinical care, assessed for the prevalence of MS.²² In the present study, we compared 4 different algorithmic estimates of CVD risks from data collected from the same patients, and combined data from such estimates with the diagnosis of MS to look for factors associated with high CV risk. Smoking provided a major independent contribution to increased CHD

Conflict of interest

The authors have no conflict of interest.

References (49)

C. Cammarosano et al.
Cardiac lesions in acquired immune deficiency syndrome (AIDS)
J Am Coll Cardiol
(1985)
K.M. Anderson et al.
Cardiovascular disease risk profiles
Am Heart J
(1991)
D. Giavarina et al.
Comparison of methods to identify individuals at increased risk of cardiovascular disease in Italian cohorts
Nutr Metab Cardiovasc Dis
(2007)
G. Schillaci et al.
Prognostic value of the metabolic syndrome in essential hypertension
J Am Coll Cardiol
(2004)
F.J. Palella et al.
Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigators
N Engl J Med
(1998)
S. Grinspoon et al.
Cardiovascular risk and body-fat abnormalities in HIV-infected adults
N Engl J Med
(2005)
P.W. Wilson et al.
Prediction of coronary heart disease using risk factor categories
Circulation
(1998)
S.M. Grundy et al.
National Heart, Lung, and Blood Institute; American College of Cardiology Foundation; American Heart Association. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines
Circulation
(2004)
J.H. Stein
Managing cardiovascular risk in patients with HIV infection
J Acquir Immune Defic Syndr
(2005)
C. Jericó et al.
Metabolic syndrome among HIV-infected patients: prevalence, characteristics, and related factors
Diabetes Care
(2005)

R. Bruno et al.

High prevalence of metabolic syndrome among HIV-infected patients: link with the cardiovascular risk

J Acquir Immune Defic Syndr

(2002)

P. Bonfanti et al.

HIV and metabolic syndrome: a comparison with the general population

J Acquir Immune Defic Syndr

(2007)

H.R. Eckel et al.

The metabolic syndrome

Lancet

(2005)

E.S. Ford

Risks for all-cause mortality, cardiovascular disease, and diabetes associated with the metabolic syndrome: a summary of the evidence

Diabetes Care

(2005)

B. Isomaa et al.

Cardiovascular morbidity and mortality associated with the metabolic syndrome

Diabetes Care

(2001)

Executive Summary of the Third Report of the National Cholesterol Educational Programme (NCEP) Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III)

JAMA

(2001)

N. Friis-Moller et al.

Class of antiretroviral drugs and the risk of myocardial infarction

N Engl J Med

(2007)

M. Mary-Krause et al.

Clinical Epidemiology Group from the French Hospital Database. Increased risk of myocardial infarction with duration of protease inhibitor therapy in HIV-infected men

AIDS

(2003)

G.V. De Socio et al.

Is estimated cardiovascular risk higher in HIV-infected patients than in the general population?

Scand J Infect Dis

(2007)

H. Knobel et al.

Global cardiovascular risk in patients with HIV infection: concordance and differences in estimates according to three risk equations (Framingham, SCORE, and PROCAM)

AIDS Patient Care STDS

(2007)

G. Assmann et al.

Simple scoring scheme for calculating the risk of acute coronary events based on the 10-year follow-up of the prospective cardiovascular Munster (PROCAM) study

Circulation

(2002)

[No authors listed]; Gruppo di Ricerca del Progetto CUORE. [The Italian Heart Project-longitudinal studies]

Ital Heart J

(2004)

R.M. Conroy et al.

Estimation of ten-year risk of fatal cardiovascular disease in Europe: the SCORE project

Eur Heart J

(2003)

P. Bonfanti et al.

CISAI Study Group. Metabolic syndrome: a real threat for HIV-positive patients?: results from the SIMONE study

J Acquir Immune Defic Syndr

(2006)

Cited by (49)

Correlation between metabolic syndrome and relative telomere length shortening in HIV/AIDS patients on combined antiretroviral therapy
2021, Experimental Gerontology
Citation Excerpt :
Patients with MetS did not differ by age and duration of cART from patients without it, which is concordant with the results reported by De Waal et al. (2013). Patients with MetS had a higher CD4 + T cell counts than those without MetS, which is also in agreement with the results reported by other authors (Mondy et al., 2007; De Socio et al., 2008). Alvarez et al. showed that the risk of MetS was higher in patients with a higher number of CD4+ T lymphocytes, that is, in patients with the best immune status and that this risk increased by 9% per 100 cells increment in CD4+ T-lymphocytes subpopulation (Alvarez et al., 2010).
Components of the metabolic syndrome (MetS) play an important role in the accelerated aging process. Relative telomere length (RTL) is a marker of biological aging. The aim of our study was to determine RTL and its possible association with MetS and the components of MetS in HIV-infected patients treated with cART.
We included 24 HIV-infected men, all Caucasians, with successful cART (<50 HIV-RNA copies/mL) and on stable cART for at least 24 months. The presence of MetS and its components was determined by the criteria prescribed by the International Diabetes Federation. RTL was determined by Real-Time PCR and ΔΔCt method. We performed a multiple linear regression modeling on log-transformed RTL (dependant variable) to evaluate which components of the metabolic syndrome as well as cART duration and cART type, had an impact on RTL.
Eleven (45.8%) patients had and 13 (54.2%) had not MetS. All patients, had an undetectable viral RNA and a relatively good immune status. The mean RTL was 0.62 ± 0.15 and 0.95 ± 0.36 in patients with and without MetS, respectively (p = 0.01). Multiple linear regression model showed no significant association between duration of cART, cART type and RTL (p = 0.2165, p = 0.8628, respectively). The same analysis showed that an increase in number of MetS components was associated with shorter telomere length (β = −0.4982, p = 0.042).
We showed for the first time association between RTL shortening in HIV-infected men with metabolic syndrome. Furthermore, our study also indicated that an increment of metabolic syndrome components is strongly associated with shorter telomere length.
Cardiovascular risk in HIV-infected individuals: A comparison of three risk prediction algorithms
2019, Revista Portuguesa de Cardiologia
Citation Excerpt :
Cardiovascular (CV) risk in the HIV-infected population has been shown to be high, an estimated 50% higher than in uninfected individuals, although some of the data are still controversial.6–11 Traditional risk factors such as smoking, which are particularly prevalent in this population, contribute to this increased risk.1,2,6,11–16 Other factors include substance abuse6 and changes in lipid profile1,8,12,15,17 and glucose metabolism, with increased insulin resistance and/or impaired insulin secretion.8,18
Cardiovascular (CV) risk is known to be increased in HIV-infected individuals. Our aim was to assess CV risk in HIV-infected adults.
CV risk was estimated for each patient using three different risk algorithms: SCORE, the Framingham risk score (FRS), and DAD. Patients were classified as at low, moderate or high CV risk. Clinical and anthropometric data were collected.
We included 571 HIV-infected individuals, mostly male (67.1%; n=383). Patients were divided into two groups according to antiretroviral therapy (ART): naïve (7.5%; n=43) or under ART (92.5%; n=528). The mean time since HIV diagnosis was 6.7±6.5 years in the naive group and 13.3±6.1 years in the ART group. Metabolic syndrome (MS) was identified in 33.9% (n=179) and 16.3% (n=7) of participants in the ART and naïve groups, respectively. MS was associated with ART (OR=2.7; p=0.018). Triglycerides ≥150 mg/dl (OR=13.643, p<0.001) was one of the major factors contributing to MS. Overall, high CV risk was found in 4.4% (n=23) of patients when the SCORE tool was used, in 20.5% (n=117) using the FRS, and in 10.3% (n=59) using the DAD score. The observed agreement between the FRS and SCORE was 55.4% (k=0.183, p<0.001), between the FRS and DAD 70.5% (k=0.465, p<0.001), and between SCORE and DAD 72.3% (k=0.347, p<0.001).
On the basis of the three algorithms, we detected a high rate of high CV risk, particularly in patients under ART. The FRS was the algorithm that classified most patients in the high CV risk category (20.5%). In addition, a high prevalence of MS was identified in this patient group.
O risco cardiovascular (RCV) pode estar aumentado em indivíduos com infeção por Vírus Imunodeficiência Humana (VIH). O objetivo deste trabalho foi avaliar o RCV em adultos infetados por VIH.
O RCV foi estimado utilizando três algoritmos diferentes, Score, Framingham Risk Score (FRSs-CVD) e DAD; os participantes foram classificados apresentando RCV baixo, moderado ou elevado. Recolheram-se dados clínicos e antropométricos.
Incluíram-se 571 indivíduos, maioritariamente do género masculino (67,1%; n=383). Dividiram-se os participantes em dois grupos, com e sem terapêutica antirretroviral (cTAR): naïve (7,5%; n=43) versus cTAR (92,5%; n=528). O tempo médio desde o diagnóstico da infeção por VIH foi 6,7±6,5 anos no grupo naïve e 13,3±6,1 anos no grupo cART. A síndrome metabólica (SM) foi identificada em 33,9% (n=179) e em 16,3% (n=7) dos participantes, respetivamente no grupo cART e no grupo naïve. Verificou-se um RCV elevado em 4,4% (n=23) dos participantes, com recurso à ferramenta Score, em 20,5% (n=117) utilizando a FRSs e em 10,3% dos participantes (n=59) utilizando a ferramenta DAD. A concordância observada entre FRSs e Score foi 55,4% (k=0,183; p<0,001), entre FRSs e DAD 70,5% (k=0,465; p<0,001) e entre Score e DAD 72,3% (k=0,347; p<0,001).
Com recurso aos algoritmos utilizados, identificou-se uma presença significativa de elevado RCV, sendo a ferramenta FRSs-CVD a que classificou mais indivíduos na categoria de RCV elevado (20,5%), e simultaneamente verificou-se uma prevalência elevada de SM.
Body fat changes and mitochondrial alterations during HBV treatment: A warning for long term administration
2012, Journal of Infection
The feature of Metabolic Syndrome in HIV naive patients is not the same of those treated: Results from a prospective study
2012, Biomedicine and Pharmacotherapy
Citation Excerpt :
In the HIV-positive population, MS is considered an emerging risk factor for overall cardiovascular risk [1–6], though different populations and ethnic groups show prevalence ranging from 7 to 45.5% [7]. In the clinical setting, diagnosing MS is useful to identify and characterize HIV-infected patients at higher cardiovascular risk [8]. Nevertheless, how antiretroviral therapy and HIV infection per se are related to MS is still unclear: to date, studies have not provided conclusive results [7].
Metabolic Syndrome (MS) is a common disorder combining obesity, dyslipidemia, hypertension, and insulin resistance. Its prevalence among HIV-infected people is still debated. Besides, how antiretroviral therapy and HIV infection per se are related to MS is still unclear. All treatment-naïve patients attending scheduled visits at CISAI group hospitals between January and December 2007 were eligible for the study. Patients without MS at enrolment were followed-up for 3 years or until they developed MS, diagnosed according to the National Cholesterol Education Program (NCEP) definition. The main objective was to assess the 3-years incidence of MS. MS was evaluated for 188 subjects. Out of them, 62 (33.0%) had started HAART at enrolment, whereas 67 (35.6%) more started during the observation. 59 (31.4%) were still treatment-naive at the study end. MS was newly diagnosed in 14 patients. The incidence was 2.60 cases/100 person-years (95% CI 1.47–4.51), 2.75 (1.11–5.72) among HAART-naïve patients and 2.65 (1.23–5.03) in subjects on HAART. Blood pressure did not change in the study period, whereas in naive patients the HDL level significantly lowered (median –6.0 vs. 4.0, P < 0.0001) compared to HAART-treated patients. Triglicerides increased significantly in HAART subjects (median 12.0 vs. 1.0, P = 0.02), as well as blood glucose (median 6.0 vs. 1.0, P = 0.01). In our population, the overall MS incidence was low and largely similar in patients who started HAART or remained naive. However, the feature of MS was different in the two groups, suggesting that in untreated and treated patients MS developed through different metabolic pathways.
An overlooked majority: HIV-positive gay men who smoke
2012, Journal of Men's Health
Citation Excerpt :
There is a growing body of research documenting the co-morbidities associated with smoking among PLWH including increased risk of chronic obstructive pulmonary disease [6,15], tuberculosis [15], lung cancer [9], emphysema [13] and bacterial pneumonia [10,12]. Smoking also compounds the risk of developing oral candidiasis and hairy leukoplakia [27,28], and it is the main independent predictor of cardiovascular disease among PLWH [7,8,14] and likely contributes to renal disease amid evidence of a dose–response relationship between number of packs smoked per day and presence of chronic kidney disease [11]. Higher frequency and severity of reported illness symptoms among gay or bisexual men [29] are associated with heavier tobacco use [29,30].
Therapeutic advances have dramatically improved health outcomes and life expectancy among persons living with HIV, but gains in life expectancy achieved by antiretroviral therapy may be mitigated by other health risk behaviours. HIV-positive gay men are especially at-risk for smoking and its adverse health risks. This scoping review summarizes evidence related to HIV and smoking, paying particular attention to gay men's masculinities as a means of providing direction for tailored tobacco cessation interventions for this vulnerable group. HIV-positive gay men face challenges with managing a complex disease and its psychological and social issues require tailored tobacco cessation interventions cognisant of the diverse social contexts in which they live. Although tobacco cessation intervention research among these men is limited, we make some recommendations to guide researchers and health care providers who work with these men.
HIV and General Cardiovascular Risk
2011, Journal of the Association of Nurses in AIDS Care
Citation Excerpt :
Therefore, under-reporting or over-reporting cannot be ruled out and may have led to inaccurate estimates. It is noteworthy that the cardiovascular risk factors reported in this study are similar to other HIV studies, which collected such data (De Socio et al., 2008; Mondy et al., 2007; Palacios et al., 2006). At this time, there is no CVD risk score equation specifically tailored for HIV.
The incidence of cardiovascular disease (CVD) is increasing in HIV-infected people. Risk factors such as hyperlipidemia, impaired glucose tolerance, and insulin resistance have become common. CVD in HIV may also be related to nontraditional risk factors including accumulation of visceral fat, inflammation secondary to HIV, and effects of some antiretroviral drugs. This cross-sectional study described the CVD risk factors of 123 adults living with HIV and calculated the 10-year estimate for general cardiovascular risk score. Results showed that approximately 25% of the participants were considered to be at high risk for developing CVD in the next 10 years. Increased waist circumference and longer duration of smoking habit were associated with elevated general cardiovascular risk scores. Similar to the general population, most of the identified risks could be modified through lifestyle management.

View all citing articles on Scopus

View full text

Identifying HIV patients with an unfavorable cardiovascular risk profile in the clinical practice: Results from the SIMONE study

Summary

Objective

Design

Methods

Results

Conclusions

Introduction

Section snippets

Patients and study design

Results

Discussion

Conflict of interest

J Am Coll Cardiol

Am Heart J

Nutr Metab Cardiovasc Dis

J Am Coll Cardiol

Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigators

N Engl J Med

Cardiovascular risk and body-fat abnormalities in HIV-infected adults

N Engl J Med

Prediction of coronary heart disease using risk factor categories

Circulation

National Heart, Lung, and Blood Institute; American College of Cardiology Foundation; American Heart Association. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines

Circulation

Managing cardiovascular risk in patients with HIV infection

J Acquir Immune Defic Syndr

Metabolic syndrome among HIV-infected patients: prevalence, characteristics, and related factors

Diabetes Care

High prevalence of metabolic syndrome among HIV-infected patients: link with the cardiovascular risk

J Acquir Immune Defic Syndr

HIV and metabolic syndrome: a comparison with the general population

J Acquir Immune Defic Syndr

The metabolic syndrome

Lancet

Risks for all-cause mortality, cardiovascular disease, and diabetes associated with the metabolic syndrome: a summary of the evidence

Diabetes Care

Cardiovascular morbidity and mortality associated with the metabolic syndrome

Diabetes Care

Executive Summary of the Third Report of the National Cholesterol Educational Programme (NCEP) Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III)

JAMA

Class of antiretroviral drugs and the risk of myocardial infarction

N Engl J Med

Clinical Epidemiology Group from the French Hospital Database. Increased risk of myocardial infarction with duration of protease inhibitor therapy in HIV-infected men

AIDS

Is estimated cardiovascular risk higher in HIV-infected patients than in the general population?

Scand J Infect Dis

Global cardiovascular risk in patients with HIV infection: concordance and differences in estimates according to three risk equations (Framingham, SCORE, and PROCAM)

AIDS Patient Care STDS

Simple scoring scheme for calculating the risk of acute coronary events based on the 10-year follow-up of the prospective cardiovascular Munster (PROCAM) study

Circulation

[No authors listed]; Gruppo di Ricerca del Progetto CUORE. [The Italian Heart Project-longitudinal studies]

Ital Heart J

Estimation of ten-year risk of fatal cardiovascular disease in Europe: the SCORE project

Eur Heart J

CISAI Study Group. Metabolic syndrome: a real threat for HIV-positive patients?: results from the SIMONE study

J Acquir Immune Defic Syndr