Cardiovascular Dis. & HIV Infection

By pharmacist Ala’a F. Alwazni

IntroductionCardiovascular abnormalities have been

reported in acquired immunodeficiency syndrome pt. (25-75%) either due to HIV infection itself or because of antiretroviral therapy mediated metabolic changes & adverse effects.

Studies suggest that:CV EVENTS ARE THE UNDERLYING

CAUSE IN MORE THAN 10% OF DEATHS IN PT. WITH HIV, & RANKS IN THE TOP 4 LEADING CAUSES OF MORTALITY (USUALLY AFTER AIDS-RELATED EVENTS, END-STAGE LIVER DIS. & MALIGNANCY).

EtiologyHIV attacks the body’s immune sys.

resulting in profound suppression of T-cell macrophage-mediated immunity & abnormal B-cell lymphocyte function, affected humoral immunity causing frequently life threatening superinfections.

HIV medications may cause conditions as dyslipidemia, diabetes or metabolic synd. Which are risk factors for heart diseases.

Conditions unrelated to HIV such as obesity, smoking, family history of heart dis., I.V. drugs & alcohol abuse may predispose pt. to heart problems.

HIV- Associated CVD

Dilated CardiomyopathyAnnual incidence of 15.9 in 1000 cases.Mortality was higher in children with baseline depressed left ventricular fractional shortening /increased left ventricular dimension, thickness, mass wall stress, heart rate or blood pressure.

HIV- Associated CVDEndocarditisBacterial infection of inner lining of the heart, starts in blood stream & spreads to the heart; fungal & viral endocarditis reported.Nonbacterial thrombotic endocarditis (marantic) occurs in 3-5% of AIDS pt. (with HIV wasting syndrome). Presentation: fever, chills, weakness, aching muscles & joints, persistent cough, hematuria, weight loss, tenderness in spleen and swelling in the legs or abdomen.

HIV- Associated CVDMyocarditis

The most frequent cause of DCM in HIV pt.HIV-1 virions infect myocardial cells in patchy distributions without clear direct association, dendritic cell possibly play a pathogenic role in the interaction between HIV-1 & the myocyte and in the activation of multifunctional cytokines (CK) that contribute to tissue damage.

HIV- Associated CVDPericarditis & Pericardial Effusion Inflammation of the sac-like membrane that surrounds the heart, caused by infection (Staphylococcus, Tuberculosis or Herpes simplex) that spreads to the heart.Presentation: chest pain, shortness of breath, fever, fatigue, dry cough & swollen legs or abdomen.Patients may have pleural effusions (occur when membrane surrounds the heart fills with fluid);due to opportunistic inf. or malignancy.

HIV- Associated CVDAutoimmunity & Malignancy

Cardiac-specific auto-antibodies (anti- α myosin auto Ab.) reported in ~30% of pt. & play a role in the pathogenesis of HIV-related heart dis.HIV patients have weakened immunity, so they have an increased risk of developing cancers that may spread to heart (rare cases) ex., Kaposi sarcoma & Lymphoma.

HIV- Associated CVDPulmonary High Blood PressureCommon among pt. with advanced HIV dis. (occur when the arteries in lung become narrowed or blocked).Pathogenesis: HIV-infection of alveolar macrophages release of (TNF-α, oxide anion & proteolytic enzymes)as well as activation of genetic factors.Presentation: varying from mild asymptomatic to sever cardiac impairment with corpulmonale and death. Symptoms include SOB, fatigue, dizziness, chest pain, bluish colored lips, increased heart beat & swelling of the ankles, legs & abdomen.

HIV- Associated CVDCoronary Artery Diseases

Inflammatory vascular dis. Including polyarteritis nodosa, Henoch-Schönlein purpura, drug-induced hypersensitivity vasculitis, Kawasaki-like syndrome & Takayasu’s arteritis have been described.The risk of developing CAD linked to cytomegalovirus or HIV itself,(even though association between viral inf. & CA lesion is not clear) as well as to ART.Presentation: chest pain, SOB, irregular heart beat, dizziness, nausea & increased sweating.

HIV- Associated CVDAtherosclerosis & Card. Abnormalities

HIV inf. Contribute to the development of atherosclerosis by causing gaps to open up in the endothelium of bl. vessels as well as inducing apoptosis of endothelial cells [inflamm. Markers correlated with internal intima media thickness (sVCAM-1, myeloperoxidase, and TNF-α) were reported in HIV pts].Common risk factor reported with cardiac abnormality in HIV pt. was malnourishment.

Nutritional DeficiencyCommon in HIV pts.(late stage dis.), contribute in induction of ventricular dysfunction independently of HAART regimens.Examples include:

Trace elements--»associated with cardiomyopathy

 Selenium--»reverse cardiomyopathy and restore left ventricular function

Vitamin B12, carnitine, and growth/ thyroid hormone ----»ass. with left vent. dysfunction

CVD Prevention & Treatment Life style modification

Lipid monitoring & tx.(pravastatin preferred for HIV pt. as well as new drugs like PPARs & Fibric acid derivatives).

MI & PHT tx. With usual anticoagulants, vasodilators & aspirin.

Immunoglobulin therapy indicated for children with cardiomyopathy

Surgical intervention reported for highly risk pt. with endocarditis/ pericardial effusion.

HIV ass. Therapies & HEART

Prolonged, high dose therapy with interferon-α, doxorubicin & foscarnet found to be associated with dilated cardiomyopathy.

Amphotericin B, ganciclovir, trimethoprim-sulfamethoxazole & pentamidine were associated with cardiac arrhythmias.

Stratified Risk of HAARTCV risk increased by 1.3-4 folds due

to metabolic changes associated with HAART; (HAART itself is recommended for prevention of CVD & increase their risk in the same time).

CV risk in ART categories are attributed to:

i. NRTIs----lactic acidosis & lipodystrophy.

ii. NNRTIs----changes of lipid profile.iii. PIs----metabolic alterations,

dyslipidemic atherogenic effect & hyper-homocysteinemia in children.

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