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Cvd n hiv

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This document discusses cardiovascular diseases in HIV patients. It notes that cardiovascular disease is more common in HIV patients due to multiple potential factors, including traditional risk factors, HIV itself, antiretroviral therapy, and chronic inflammation. It also discusses specific cardiac complications in more detail, such as cardiomyopathy, pericardial effusion, endocarditis, pulmonary hypertension, vasculitis, and the possible association between viral infections and coronary artery disease.

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HEART DISEASES IN HIV DR K. BHATTACHARJEE(ASSOCIATE PROFESSOR)
OUTLINE - There are data suggesting increased risk of CVD in people with HIV - CVD clearly more common with HIV - What is unclear? why? -Possibilities • More risk factors (smoking, sedentariness, stress, depression) • HIV (via immune and inflammatory mechanisms, microbial translocation, CMV) • ART
Cvd n hiv
Traditional risk factors cART toxicity Coinfection with eg CMV Monocyte and mϕ activation Other proinflammatory and procoagulant pathways Cardiovascular disease Chronic inflammation Contributing Factors to CVD in HIV+ Pts
Chronic Inflammation and Increased Risk for Comorbidities in HIV-Positive Pts Untreated HIV Infection Loss of immunoregulatory cellsn HIV replication Loss of gut mucosal integrity and microbial translocation Decreased but persistent chronic inflammation, immune activation, elevated coagulation markers, microbial translocation, and increased risk of coinfection Increased incidence of comorbidities and clinical disease ART Traditional comorbidity risk factors, such as dyslipidemia, smoking, lipodystrophy, HTN, obesity, substance use
HIV-infected patients Non-HIV-infected patients (A) HAART-induced dyslipidemia, hypertriglyceridemia, HDL reduction, especially if PI used Fat abnormal metabolism leading to hypertriglyceridemia and dyslipidemia (B) HAART-induced leptin deficiency and hypoadiponectinemia leading to insulin resistance Hypoadiponectinemia leading to insulin resistance and abnormal glucose metabolism (C) HIV-associated “lipodystrophy” syndrome—body fat abnormalities—fat accumulation around the neck, dorsocervical region as “buffalo hump,” abdomen, and trunk Waist circumference enlargement due to abdominal fat accumulation
Potential mechanisms of cardiac complications in AIDS Mechanism Effect Direct infection of cardiac myocytes Cardiomyopathy/myocarditis Toxicity of HIV components Impaired myocardial contractility Immune processes involving MHC I, anti-α- myosin Ab, cytokines Cardiomyopathy and endothelial dysfunction Nutritional deficiencies (carnitine, Se, thiamine) Cardiomyopathy Drug toxicity (HAART, antifungals, antivirals) Cardiomyopathy, conduction disorders, glucose intolerance, CAD, CVA
• Asymptomatic or symptomatic cardiovascular disease with normal initial ECHO – repeat ECHO every 1-2 years if asymptomatic. • Initial ECHO is abnormal – Rx of CCF if systolic dysfunction, investigate and manage pericardial effusion, consider HAART, specific management for mass or vegetation. • LV systolic dysfunction in clinically stable patients – repeat ECHO after 2 weeks. • If repeat ECHO at 2 weeks shows improvement and patient continues to improve clinically – yearly ECHO. • Persistent or worsened systolic function – consider endomyocardial biopsy, CAG, immunomodulatory therapy. Guidelines for monitoring cardiac dysfunction in patients with HIV
Treatment of Hyperlipidemia in HIV Infected Patients
• This is complex • Clear signals for role of discrimination in risk of CVD • There are underlying psychosocial, genetic, and sex differences in one’s susceptibility to exposure to discrimination • Depression is major co-occurrence • Discrimination is a factor that needs to be included in CVD research Take Home message
Cardiomyopathy and pericardial effusion: HIV/AIDS is recognized as an important cause of dilated cardiomyopathy, with an estimated annual incidence of 15.9/1,000 before the introduction of HAART1. This incidence is mainly related to that of myocarditis, which is still the best-studied cause of dilated cardiomyopathy in HIV/AIDS. Myocarditis has been documented at autopsy in 40-52 per cent of patients who died of AIDS before the introduction of HAART2. Another important cause of cardiomyopathy in HIV/AIDS is drug cardiotoxicity. Zidovudine is associated with diffuse destruction of cardiac mi-tochondrial ultrastructure and inhibition of mito- chondrial DNA replication that may contribute to myocardial cell dys-function3. Doxorubicin (adria-mycin), which is used to treat AIDS-associated Kaposi's sarcoma and non-Hodgkin's lymphoma, has a dose-related effect on dilated cardiomyopathy4, as does foscarnet sodium when used to treat cyto-megalovirus oesophagitis5.
Endocarditis: The prevalence of infective endocarditis did not vary in HIV-infected patients who use intravenous drugs after the introduction of HAART even in the developed countries, being similar to that observed in HIV-uninfected intravenous drug addicts1. Among intravenous drug addicts, the tricuspid valve is most frequently affected and the most frequent agents are Staphylococcus aureus (>75% of cases),Streptococcus pneumoniae, Haemophilus influenzae, Candida albicans, Aspergillus fumigatus andCryptococcus neoformans2. A virulent bacteria, as the HACEK group (Haemophilus species, Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens and Kingella kingae), which are often part of the endogenous flora of the mouth, can cause endocarditis in HIV-infected patients12. A prevalence of 3-5 per cent of non-bacterial thrombotic endocarditis, also known as marantic endocarditis was seen in AIDS patients, mostly with HIV-wasting syndrome, before the introduction of HAART2. Marantic endocarditis is now more frequently observed in developing countries with a high incidence (about 10-15%) and mortality for systemic embolization
Pulmonary hypertension: The incidence of HIV-associated pulmonary hypertension is increased in HIV-infected patients after the introduction of HAART. It has been estimated in 1/200, much higher than 1/200,000 found in the general population13. A key pathogenetic role in this condition is played by pulmonary dendritic cells which are not sensitive to HAART and may hold HIV- 1 on their surfaces for extended time periods. The infection of these cells by HIV-1 causes a chronic release of cytotoxic cytokines (e.g., endothelin-1, interleukin-6, interleukin-1 beta and TNF- alpha) contributing to vascular plexogenic lesions and progressive tissue damage and congestive heart failure, independently of opportunistic infections, stage of HIV disease and HAART regimens13. Endothelin-1 receptor antagonists, such as bosentan, may be useful, even in combination with HAART in the early stages of the disease14,15. The use of phosphodiesterase-5 inhibitors (e.g., sildenafil), although promising, is still debated because of their interaction with protease inhibitors.
Vasculitis: A wide range of inflammatory vascular diseases including polyarteritis nodosa, Henoch-Schonlein purpura, and drug-induced hypersensitivity vasculitis may develop in HIV-infected individuals. Kawasaki-like syndrome16,17 and Takayasu's arteritis18 have also been described. Some HIV- infected patients have a clinical presentation resembling systemic lupus erythematosus with arthralgias, myalgias, and autoimmune phenomena with a low titre positive antinuclear antibody, coagulopathy with lupus anticoagulant, haemolytic anaemia, and thrombocytopenic purpura19. Drug-induced hypersensitivity vasculitis is common in HIV-infected patients receiving HAART19.The vasculitis associated with drug reactions typically involves small vessels and has a lymphocytic or leukocytoclastic histopathology. Medical practitioners need to be especially aware of abacavir hypersensitivity reactions because of the potential for fatal outcomes. Hypersensitivity reactions of this type should always be considered as a possible aetiology for a vasculitic syndrome in an HIV-infected patient19.
Viral infection and coronary artery disease: The association between viral infection (cytomegalovirus or HIV-1 itself) and coronary artery lesions is not clear. HIV-1 sequences have been detected by in situhybridization in the coronary vessels of an HIV-infected patient who died from acute myocardial infarction20. Po-tential mechanisms through which HIV-1 may damage cor-onary arteries include activation of cytokines and cell-adhesion molecules and alteration of major- histocompatibility-complex (MHC) class I molecules on the surface of smooth-muscle cells20. It is possible also that HIV-1- associated protein gp 120 may induce smooth-muscle cell apoptosis through a mitochondrion-controlled pathway by activation of inflammatory cytokines21.
Cvd n hiv

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Cvd n hiv

  • 1. HEART DISEASES IN HIV DR K. BHATTACHARJEE(ASSOCIATE PROFESSOR)
  • 2. OUTLINE - There are data suggesting increased risk of CVD in people with HIV - CVD clearly more common with HIV - What is unclear? why? -Possibilities • More risk factors (smoking, sedentariness, stress, depression) • HIV (via immune and inflammatory mechanisms, microbial translocation, CMV) • ART
  • 4. Traditional risk factors cART toxicity Coinfection with eg CMV Monocyte and mϕ activation Other proinflammatory and procoagulant pathways Cardiovascular disease Chronic inflammation Contributing Factors to CVD in HIV+ Pts
  • 5. Chronic Inflammation and Increased Risk for Comorbidities in HIV-Positive Pts Untreated HIV Infection Loss of immunoregulatory cellsn HIV replication Loss of gut mucosal integrity and microbial translocation Decreased but persistent chronic inflammation, immune activation, elevated coagulation markers, microbial translocation, and increased risk of coinfection Increased incidence of comorbidities and clinical disease ART Traditional comorbidity risk factors, such as dyslipidemia, smoking, lipodystrophy, HTN, obesity, substance use
  • 6. HIV-infected patients Non-HIV-infected patients (A) HAART-induced dyslipidemia, hypertriglyceridemia, HDL reduction, especially if PI used Fat abnormal metabolism leading to hypertriglyceridemia and dyslipidemia (B) HAART-induced leptin deficiency and hypoadiponectinemia leading to insulin resistance Hypoadiponectinemia leading to insulin resistance and abnormal glucose metabolism (C) HIV-associated “lipodystrophy” syndrome—body fat abnormalities—fat accumulation around the neck, dorsocervical region as “buffalo hump,” abdomen, and trunk Waist circumference enlargement due to abdominal fat accumulation
  • 7. Potential mechanisms of cardiac complications in AIDS Mechanism Effect Direct infection of cardiac myocytes Cardiomyopathy/myocarditis Toxicity of HIV components Impaired myocardial contractility Immune processes involving MHC I, anti-α- myosin Ab, cytokines Cardiomyopathy and endothelial dysfunction Nutritional deficiencies (carnitine, Se, thiamine) Cardiomyopathy Drug toxicity (HAART, antifungals, antivirals) Cardiomyopathy, conduction disorders, glucose intolerance, CAD, CVA
  • 8. • Asymptomatic or symptomatic cardiovascular disease with normal initial ECHO – repeat ECHO every 1-2 years if asymptomatic. • Initial ECHO is abnormal – Rx of CCF if systolic dysfunction, investigate and manage pericardial effusion, consider HAART, specific management for mass or vegetation. • LV systolic dysfunction in clinically stable patients – repeat ECHO after 2 weeks. • If repeat ECHO at 2 weeks shows improvement and patient continues to improve clinically – yearly ECHO. • Persistent or worsened systolic function – consider endomyocardial biopsy, CAG, immunomodulatory therapy. Guidelines for monitoring cardiac dysfunction in patients with HIV
  • 9. Treatment of Hyperlipidemia in HIV Infected Patients
  • 10. • This is complex • Clear signals for role of discrimination in risk of CVD • There are underlying psychosocial, genetic, and sex differences in one’s susceptibility to exposure to discrimination • Depression is major co-occurrence • Discrimination is a factor that needs to be included in CVD research Take Home message
  • 11. Cardiomyopathy and pericardial effusion: HIV/AIDS is recognized as an important cause of dilated cardiomyopathy, with an estimated annual incidence of 15.9/1,000 before the introduction of HAART1. This incidence is mainly related to that of myocarditis, which is still the best-studied cause of dilated cardiomyopathy in HIV/AIDS. Myocarditis has been documented at autopsy in 40-52 per cent of patients who died of AIDS before the introduction of HAART2. Another important cause of cardiomyopathy in HIV/AIDS is drug cardiotoxicity. Zidovudine is associated with diffuse destruction of cardiac mi-tochondrial ultrastructure and inhibition of mito- chondrial DNA replication that may contribute to myocardial cell dys-function3. Doxorubicin (adria-mycin), which is used to treat AIDS-associated Kaposi's sarcoma and non-Hodgkin's lymphoma, has a dose-related effect on dilated cardiomyopathy4, as does foscarnet sodium when used to treat cyto-megalovirus oesophagitis5.
  • 12. Endocarditis: The prevalence of infective endocarditis did not vary in HIV-infected patients who use intravenous drugs after the introduction of HAART even in the developed countries, being similar to that observed in HIV-uninfected intravenous drug addicts1. Among intravenous drug addicts, the tricuspid valve is most frequently affected and the most frequent agents are Staphylococcus aureus (>75% of cases),Streptococcus pneumoniae, Haemophilus influenzae, Candida albicans, Aspergillus fumigatus andCryptococcus neoformans2. A virulent bacteria, as the HACEK group (Haemophilus species, Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens and Kingella kingae), which are often part of the endogenous flora of the mouth, can cause endocarditis in HIV-infected patients12. A prevalence of 3-5 per cent of non-bacterial thrombotic endocarditis, also known as marantic endocarditis was seen in AIDS patients, mostly with HIV-wasting syndrome, before the introduction of HAART2. Marantic endocarditis is now more frequently observed in developing countries with a high incidence (about 10-15%) and mortality for systemic embolization
  • 13. Pulmonary hypertension: The incidence of HIV-associated pulmonary hypertension is increased in HIV-infected patients after the introduction of HAART. It has been estimated in 1/200, much higher than 1/200,000 found in the general population13. A key pathogenetic role in this condition is played by pulmonary dendritic cells which are not sensitive to HAART and may hold HIV- 1 on their surfaces for extended time periods. The infection of these cells by HIV-1 causes a chronic release of cytotoxic cytokines (e.g., endothelin-1, interleukin-6, interleukin-1 beta and TNF- alpha) contributing to vascular plexogenic lesions and progressive tissue damage and congestive heart failure, independently of opportunistic infections, stage of HIV disease and HAART regimens13. Endothelin-1 receptor antagonists, such as bosentan, may be useful, even in combination with HAART in the early stages of the disease14,15. The use of phosphodiesterase-5 inhibitors (e.g., sildenafil), although promising, is still debated because of their interaction with protease inhibitors.
  • 14. Vasculitis: A wide range of inflammatory vascular diseases including polyarteritis nodosa, Henoch-Schonlein purpura, and drug-induced hypersensitivity vasculitis may develop in HIV-infected individuals. Kawasaki-like syndrome16,17 and Takayasu's arteritis18 have also been described. Some HIV- infected patients have a clinical presentation resembling systemic lupus erythematosus with arthralgias, myalgias, and autoimmune phenomena with a low titre positive antinuclear antibody, coagulopathy with lupus anticoagulant, haemolytic anaemia, and thrombocytopenic purpura19. Drug-induced hypersensitivity vasculitis is common in HIV-infected patients receiving HAART19.The vasculitis associated with drug reactions typically involves small vessels and has a lymphocytic or leukocytoclastic histopathology. Medical practitioners need to be especially aware of abacavir hypersensitivity reactions because of the potential for fatal outcomes. Hypersensitivity reactions of this type should always be considered as a possible aetiology for a vasculitic syndrome in an HIV-infected patient19.
  • 15. Viral infection and coronary artery disease: The association between viral infection (cytomegalovirus or HIV-1 itself) and coronary artery lesions is not clear. HIV-1 sequences have been detected by in situhybridization in the coronary vessels of an HIV-infected patient who died from acute myocardial infarction20. Po-tential mechanisms through which HIV-1 may damage cor-onary arteries include activation of cytokines and cell-adhesion molecules and alteration of major- histocompatibility-complex (MHC) class I molecules on the surface of smooth-muscle cells20. It is possible also that HIV-1- associated protein gp 120 may induce smooth-muscle cell apoptosis through a mitochondrion-controlled pathway by activation of inflammatory cytokines21.