Cardiovascular Disease Risk Factors in HIV Patients

A Prospective Cohort Analysis among HIV Patients on Non Protease Inhibitor Based Antiretroviral

Therapy

A.A.I.N Jayasekara

A.A.I.N Jayasekara A.V.S.N.D Ranasinhe

Neushka HerathH.A.C.W Hathurusinghe

L.N SiriwardenaD.M.M.P.K pathiraja

M.K.S.H Jayasena N.D.V N Jayasuriya

DACL Dalugama K.A.M Ariyarathne

Senior Registrars, Post Graduate Institute of Medicine, University of Colombo, Sri Lanka 2. Medical Intern, National Hospital Sri Lanka 3. Consultant

Venereologists,National STD/AIDS Control Programme, Sri Lanka

Introduction In Sri Lanka Percentage of all deaths due to

cardiovascular disease (CVD) in 2008 - 29.6 %

The recent estimates for mortality from CVD for Sri Lanka was 524 deaths per 100,000 which is higher than that observed in many high-income countries

Coronary artery disease (CAD) is the leading cause of death in Sri Lanka while stroke is the third cause of death

For comparison, CAD accounts for only 17% of deaths in the US and UK

Between 2005 and 2010 and beyond, significant increase in hospitalization is projected for three diseases: HD 29%, DM 36%, and HT 40%

The CAD risk factors are high and increasing: DM 7%, HT 27%, obesity 18%, high cholesterol 17%, and abdominal obesity 50%

Median body mass index (BMI) was 20 units smoking was very high at 58%

A large national study in Sri Lanka has demonstrated that living in urban areas is associated with 2-3 fold rate of physical inactivity, obesity, and diabetes

Reference : Allender S, Wickramasinghe K, Goldacre M, Matthews D, Katulanda P. Quantifying Urbanization as a Risk Factor for Noncommunicable Disease. J Urban Health. Jun 3 2011

Objective

To estimate the emergence of cardiovascular disease (CVD) adverse events among HIV-infected persons who are on non PI based ARV regimen

Methods

Baseline data from 120 subjects enrolled, a prospective cohort study initiated in 2012

Assessment of CVD risk factors and calculation of the Framingham score was done as a baseline

Cohort was followed up for 30 months to see any development of adverse cardiovascular outcomes

Data was collected based on following variables

Age and sex ART regimen and duration CD4 counts Height/ weight and BMI Lipid profiles History of CVA History of gycemic control Treatment history … Hypertension, DM, Statins.. Alcohol and Smoking

Measured CVA outcomes were 1. Coronary heart disease (CHD): Myocardial

infarction (MI), angina pectoris, heart failure(HF), and coronary death

2. Cerebrovascular disease, stroke and transient ischemic attack (TIA)

3. Peripheral arterial disease, intermittent claudication and significant limb ischemia

4. Aortic disease: Aortic atherosclerosis, thoracic aortic aneurysm, and abdominal aortic aneurysm

Calculated the Framingham Score for all the patients to estimate risk of CVD in 10 years.

(updated version of Framingham General Cardiovascular Risk Score 2008)

Following parameters were assessed 1. Dyslipidemia2. Age range3. Hypertension treatment4. Smoking5. Total cholesterol

Framingham Risk Score for Women

Age: 20–34 years: Minus 7 points. 35–39 years: Minus 3 points. 40–44 years: 0 points. 45–49 years: 3 points. 50–54 years: 6 points. 55–59 years: 8 points. 60–64 years: 10 points. 65–69 years: 12 points. 70–74 years: 14 points. 75–79 years: 16 points

Total cholesterol, mg/dL: Age 20–39 years: Under 160: 0 points. 160-199: 4 points. 200-239: 8 points. 240-279: 11 points. 280 or higher: 13 points. • Age 40–49 years: Under 160: 0 points. 160-199: 3 points. 200-239: 6 points. 240-279: 8 points. 280 or higher: 10 points. • Age 50–59 years: Under 160: 0 points. 160-199: 2 points. 200-239: 4 points. 240-279: 5 points. 280 or higher: 7 points. • Age 60–69 years: Under 160: 0 points. 160-199: 1 point. 200-239: 2 points. 240-279: 3 points. 280 or higher: 4 points. • Age 70–79 years: Under 160: 0 points. 160-199: 1 point. 200-239: 1 point. 240-279: 2 points. 280 or higher: 2 points.

If cigarette smoker: Age 20–39 years: 9 points. • Age 40–49 years: 7 points. • Age 50–59 years: 4 points. • Age 60–69 years: 2 points. • Age 70–79 years: 1 point.

All non smokers: 0 points

HDL cholesterol, mg/dL: 60 or higher: Minus 1 point. 50-59: 0 points. 40-49: 1 point. Under 40: 2 points

Systolic blood pressure, mm Hg: Untreated: Under 120: 0 points. 120-129: 1 point. 130-139: 2 points. 140-159: 3 points. 160 or higher: 4 points. • Treated: Under 120: 0 points. 120-129: 3 points. 130-139: 4 points. 140-159: 5 points. 160 or higher: 6 points

10-year risk in % for Females

Under 19 points <1020 points 1121 points 1422 points 1723 points 2224 points 27>25 points Over 30

Framingham Risk Score for Men Age: 20–34 years: Minus 9 points. 35–39 years: Minus 4 points. 40–44 years: 0 points.

45–49 years: 3 points. 50–54 years: 6 points. 55–59 years: 8 points. 60–64 years: 10 points. 65–69 years: 11 points. 70–74 years: 12 points. 75–79 years: 13 points

Total cholesterol, mg/dL: Age 20–39 years: Under 160: 0 points. 160-199: 4 points. 200-239: 7 points. 240-279: 9 points. 280 or higher: 11 points. • Age 40–49 years: Under 160: 0 points. 160-199: 3 points. 200-239: 5 points. 240-279: 6 points. 280 or higher: 8 points. • Age 50–59 years: Under 160: 0 points. 160-199: 2 points. 200-239: 3 points. 240-279: 4 points. 280 or higher: 5 points. • Age 60–69 years: Under 160: 0 points. 160-199: 1 point. 200-239: 1 point. 240-279: 2 points. 280 or higher: 3 points. • Age 70–79 years: Under 160: 0 points. 160-199: 0 points. 200-239: 0 points. 240-279: 1 point. 280 or higher: 1 point.

If cigarette smoker: Age 20–39 years: 8 points. • Age 40–49 years: 5 points. • Age 50–59 years: 3 points. • Age 60–69 years: 1 point. • Age 70–79 years: 1 point.

All non smokers: 0 points

HDL cholesterol, mg/dL: 60 or higher: Minus 1 point. 50-59: 0 points. 40-49: 1 point. Under 40: 2 points

Systolic blood pressure, mm Hg: Untreated: Under 120: 0 points. 120-129: 0 points. 130-139: 1 point. 140-159: 1 point. 160 or higher: 2 points. • Treated: Under 120: 0 points. 120-129: 1 point. 130-139: 2 points. 140-159: 2 points. 160 or higher: 3 points

10-year risk in % for Males

Under 11 points <10%12 points 10%13 points 12%14 points 16%15 points 20%17 points or more over 30%

Estimated Risk levels

Low risk (<10% 10-year risk)

Intermediate (10–20% risk)

High risk category (≧ 20% risk)

Results

The mean age of the study cohort was 46.9 years

25% of the study population was at an age where there is an appreciable risk of CVD

53.2% were males and 46.8% were females

05

101520253035404550

20-34 35-39 40-44 45-49 50-54 55-59 60-64 65-70 >70

Male Female

Results cont.. All on NRTI plus NNRTI based

regimen over a mean 6.8 years (range 2-13 yrs) with SD 2.89 Yrs

79 on AZT, 29 on TDF and 1 on ABC based NRTIs

97 on EFV & 12 on NVP as NNRTI

Mean baseline CD4 count was 600 cells/mm ( median 569) and that was not statistically significant after 30 months (mean 674 cells/ql, median 635 cells/ql p=0.4)

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2 Years 2-4 Years 4-6 Years 6-8 Years 8-10Years

10-12Years

>13Years

Total cholesterol level (p= 0.32), triglycerides (p= 0.94), HDLs (p= 0.22) and LDLs (p= 0.91) were not subjected to change over a period of 30 months

The baseline BMI (mean 22.6) was not significantly different after 30 months (mean 22.4, p= 0.66)

41.8% were cigarette smokers

Results…

Thirty two individuals were started on lipid lowering drugs and all of them were belongs to the above 55 age group

21 ( 19%) Diagnosed HT & on medical management

34% were physically inactive and they were regularly advised on diet and exercise

Results…

Only one person developed a myocardial infarction

Two (1.8 %)persons developed diabetes

Thirteen (11.92%)developed unstable angina and currently under medical management

None were reported with CVA, peripheral arterial disease or aortic diseases

Results…

FRS identified majority of individuals as low risk (<10% 10-year risk) i.e. before 81 % /after 79%

13% Vs 12% with intermediate (10–20% risk)

8% belongs to the high risk category after the intervention (≧ 20% risk)

We lost 11 patients during this follow up. All deaths were not related to CVA events

Results …

The lady who developed a MI had an intermediate risk

Almost all the patients who developed UA were belongs to very low risk category at the time of enrolment

All the patients who categorized as high risk were put on statins during this follow up

None developed CV adverse events

Conclusion…

Although the cohort exhibited multiple known risk factors for CVD the incidence of developing an adverse cardiovascular event is low during this follow up period

Limitations..

Small sample size

Need further follow up

Need a control to compare the effects of non PI based ART regimens among HIV cohort

FS is validated for HIV patients, but there is a HIV specific prediction tool (Not validated yet)

Acknowledgement

Dr. Kulasiri Budhakoraka Consultant Venereologist, Ex. HIV care coordinator

Dr. Lilani Rajapakse Consultant Venereologist HIV care coordinator, NSACP, Sri Lanka

HIV Clinic staff, NSACP, Colombo

Thank you