Diabetes Mellitus, Preexisting Coronary Heart Disease, and the Risk of Subsequent Coronary Heart Disease Events in Patients Infected With Human Immunodeficiency Virus: The Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D Study)

Background— Although guidelines in individuals not infected with the human immunodeficiency virus (HIV) consider diabetes mellitus (DM) to be a coronary heart disease (CHD) equivalent, there is little information on its association with CHD in those infected with HIV. We investigated the impact of DM and preexisting CHD on the development of a new CHD episode among 33 347 HIV-infected individuals in the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D Study). Methods and Results— Over 159 971 person-years, 698 CHD events occurred. After adjustment for gender, age, cohort, HIV transmission, ethnicity, family history of CHD, smoking, and calendar year, the rate of a CHD episode was 7.52 times higher (Poisson regression, 95% CI 6.02 to 9.39, P=0.0001) in those with preexisting CHD than in those without preexisting CHD, but it was only 2.41 times higher (95% CI 1.91 to 3.05, P=0.0001) in those with preexisting DM compared with those without DM. No statistical interactions were apparent between either diagnosis and sex; although older people with DM had an increased CHD rate compared with younger people, older people with preexisting CHD had a lower event rate. A statistically significant interaction between preexisting DM and CHD (P=0.003) suggested that the CHD rate in those with preexisting CHD and DM is lower than expected on the basis of the main effects alone. Conclusions— DM and preexisting CHD are both important risk factors for CHD events in HIV-infected individuals. There is a need for targeted interventions to reduce the risk of CHD in both high-risk groups of HIV-infected individuals.

[1]  S. El-Kamary,et al.  All-cause, liver-related, and non-liver-related mortality among HCV-infected individuals in the general US population. , 2011, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[2]  J. Sterne,et al.  The Coding Causes of Death in HIV (CoDe) Project: Initial Results and Evaluation of Methodology , 2011, Epidemiology.

[3]  R. Weber,et al.  Influence of antiretroviral therapy on liver disease , 2011, Current opinion in HIV and AIDS.

[4]  R. Weber,et al.  Risk Factors for Fatality in HIV-Infected Patients with Dideoxynucleoside-Induced Severe Hyperlactataemia or Lactic Acidosis , 2011, Antiviral Therapy.

[5]  O. Kirk,et al.  Factors associated with specific causes of death amongst HIV-positive individuals in the D:A:D study , 2010, AIDS.

[6]  V. Soriano,et al.  Noncirrhotic portal hypertension in HIV-infected patients: unique clinical and pathological findings , 2010, AIDS.

[7]  N. Ford,et al.  Nevirapine-Associated Early Hepatotoxicity: Incidence, Risk Factors, and Associated Mortality in a Primary Care ART Programme in South Africa , 2010, PloS one.

[8]  P. O S I T I O N S T A T E M E N T,et al.  Diagnosis and Classification of Diabetes Mellitus , 2011, Diabetes Care.

[9]  C. Sabin,et al.  Non-AIDS-defining deaths and immunodeficiency in the era of combination antiretroviral therapy , 2009, AIDS.

[10]  R. Weber,et al.  Association of noncirrhotic portal hypertension in HIV-infected persons and antiretroviral therapy with didanosine: a nested case-control study. , 2009, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[11]  J. Blanco,et al.  Idiopathic Portal Hypertension in Patients With HIV Infection Treated With Highly Active Antiretroviral Therapy , 2009, The American Journal of Gastroenterology.

[12]  P. Morlat,et al.  Liver‐related deaths in HIV‐infected patients between 1995 and 2005 in the French GERMIVIC Joint Study Group Network (Mortavic 2005 Study in collaboration with the Mortalité 2005 survey, ANRS EN19) * , 2009, HIV medicine.

[13]  R. Tubiana,et al.  Liver damage underlying unexplained transaminase elevation in human immunodeficiency virus‐1 mono‐infected patients on antiretroviral therapy , 2009, Hepatology.

[14]  R. Weber,et al.  Self-reported alcohol consumption and its association with adherence and outcome of antiretroviral therapy in the Swiss HIV Cohort Study , 2008, Antiviral therapy.

[15]  N. Unwin,et al.  Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) Detection, Evaluation, and Treatment of High Blood Cholesterol Education Program (NCEP) Expert Panel on Executive Summary of the Third Report of the National , 2009 .

[16]  R. Shrestha,et al.  Noncirrhotic portal hypertension in patients with human immunodeficiency virus-1 infection. , 2008, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[17]  P. Morlat,et al.  Changes in Causes of Death Among Adults Infected by HIV Between 2000 and 2005: The “Mortalité 2000 and 2005” Surveys (ANRS EN19 and Mortavic) , 2008, Journal of acquired immune deficiency syndromes.

[18]  G. Ligabue,et al.  Nonalcoholic fatty liver disease in HIV-infected patients referred to a metabolic clinic: prevalence, characteristics, and predictors. , 2008, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[19]  P. Wilson,et al.  Initiative to Decrease Cardiovascular Risk and Increase Quality of Care for Patients Living With HIV/AIDS Executive Summary , 2008 .

[20]  A. Vaag,et al.  Diabetes Patients Requiring Glucose-Lowering Therapy and Nondiabetics With a Prior Myocardial Infarction Carry the Same Cardiovascular Risk: A Population Study of 3.3 Million People , 2008, Circulation.

[21]  O. Kirk,et al.  Changes over time in risk factors for cardiovascular disease and use of lipid-lowering drugs in HIV-infected individuals and impact on myocardial infarction. , 2008, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[22]  Nina Friis-Møller,et al.  Incidence and Risk Factors for New-Onset Diabetes in HIV-Infected Patients , 2008, Diabetes Care.

[23]  P. Reiss,et al.  Zidovudine/lamivudine contributes to insulin resistance within 3 months of starting combination antiretroviral therapy , 2008, AIDS.

[24]  P. Zimmet,et al.  Diagnosis and classification of diabetes mellitus , 2002 .

[25]  T. Schiano,et al.  Hepatoportal Sclerosis as a Cause of Noncirrhotic Portal Hypertension in Patients With HIV , 2007, The American Journal of Gastroenterology.

[26]  D. Cheng,et al.  Alcohol Consumption and HIV Disease Progression , 2007, Journal of acquired immune deficiency syndromes.

[27]  W. Frontera,et al.  Effects of a nucleoside reverse transcriptase inhibitor, stavudine, on glucose disposal and mitochondrial function in muscle of healthy adults. , 2007, American journal of physiology. Endocrinology and metabolism.

[28]  O. Kirk,et al.  Class of antiretroviral drugs and the risk of myocardial infarction. , 2007, The New England journal of medicine.

[29]  K. Yarasheski,et al.  Metabolic syndrome in HIV-infected patients from an urban, midwestern US outpatient population. , 2007, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[30]  D. Mohr,et al.  Clinical Depression Versus Distress Among Patients With Type 2 Diabetes , 2007, Diabetes Care.

[31]  S. Pol,et al.  Nodular regenerative hyperplasia is a new cause of chronic liver disease in HIV-infected patients , 2007, AIDS.

[32]  J. Fellay,et al.  Adverse events to antiretrovirals in the Swiss HIV Cohort Study: effect on mortality and treatment modification. , 2007, Antiviral therapy.

[33]  Richard D Moore,et al.  Hazardous Alcohol Use: A Risk Factor for Non-Adherence and Lack of Suppression in HIV Infection , 2006, Journal of acquired immune deficiency syndromes.

[34]  M. Schambelan,et al.  Single-dose lopinavir-ritonavir acutely inhibits insulin-mediated glucose disposal in healthy volunteers. , 2006, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[35]  R. Weber,et al.  Prevalence of risk factors for cardiovascular disease in HIV‐infected patients over time: the Swiss HIV Cohort Study , 2006, HIV medicine.

[36]  O. Kirk,et al.  Liver-related deaths in persons infected with the human immunodeficiency virus: the D:A:D study. , 2006, Archives of internal medicine.

[37]  L. Rabeneck,et al.  Medical Disease and Alcohol Use Among Veterans With Human Immunodeficiency Infection: A Comparison of Disease Measurement Strategies , 2006, Medical care.

[38]  P. Sax,et al.  Hepatic steatosis is associated with fibrosis, nucleoside analogue use, and hepatitis C virus genotype 3 infection in HIV-seropositive patients. , 2006, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[39]  C. Toro,et al.  Severe Liver Disease Associated With Prolonged Exposure to Antiretroviral Drugs , 2006, Journal of acquired immune deficiency syndromes.

[40]  Seppo Lehto,et al.  Type 2 diabetes as a "coronary heart disease equivalent": an 18-year prospective population-based study in Finnish subjects. , 2005, Diabetes care.

[41]  A. Mocroft,et al.  Is there evidence for an increase in the death rate from liver-related disease in patients with HIV? , 2005, AIDS.

[42]  Jesús Santos,et al.  Atherogenic lipid profile and cardiovascular risk factors in HIV-infected patients (Nétar Study). , 2005, International journal of STD & AIDS.

[43]  S. Cole,et al.  Cumulative exposure to nucleoside analogue reverse transcriptase inhibitors is associated with insulin resistance markers in the Multicenter AIDS Cohort Study , 2005, AIDS.

[44]  M. Lederman,et al.  Severe hepatotoxicity associated with nevirapine use in HIV-infected subjects. , 2005, The Journal of infectious diseases.

[45]  G. L’italien,et al.  Protease inhibitor exposure and increased risk of cardiovascular disease in HIV‐infected patients , 2005, HIV medicine.

[46]  P. Hruz,et al.  A Structural Basis for the Acute Effects of HIV Protease Inhibitors on GLUT4 Intrinsic Activity* , 2004, Journal of Biological Chemistry.

[47]  O. Kirk,et al.  Cardio- and cerebrovascular events in HIV-infected persons , 2004, AIDS.

[48]  Lynn E Eberly,et al.  Impact of diabetes and previous myocardial infarction on long-term survival: 25-year mortality follow-up of primary screenees of the Multiple Risk Factor Intervention Trial. , 2004, Archives of internal medicine.

[49]  R. D'Agostino,et al.  The significant effect of diabetes duration on coronary heart disease mortality: the Framingham Heart Study. , 2004, Diabetes care.

[50]  J. Pankow,et al.  Cardiovascular Events in Diabetic and Nondiabetic Adults With or Without History of Myocardial Infarction , 2004, Circulation.

[51]  Rodolphe Thiébaut,et al.  Combination antiretroviral therapy and the risk of myocardial infarction , 2003 .

[52]  J. Shaw,et al.  Follow-up report on the diagnosis of diabetes mellitus. , 2003, Diabetes care.

[53]  L. Bouter,et al.  Cardiovascular events in type 2 diabetes: comparison with nondiabetic individuals without and with prior cardiovascular disease. 10-year follow-up of the Hoorn Study. , 2003, European heart journal.

[54]  D. Arveiler,et al.  Risk factors for coronary heart disease in patients treated for human immunodeficiency virus infection compared with the general population. , 2003, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[55]  O. Kirk,et al.  Cardiovascular disease risk factors in HIV patients – association with antiretroviral therapy. Results from the DAD study , 2003, AIDS.

[56]  F. Hu,et al.  The impact of diabetes and prediabetes on risk of cardiovascular disease and mortality. , 2002, Drugs of today.

[57]  E. Rimm,et al.  The impact of diabetes mellitus and prior myocardial infarction on mortality from all causes and from coronary heart disease in men. , 2002, Journal of the American College of Cardiology.

[58]  Jixian Wang,et al.  Comparison of cardiovascular risk between patients with type 2 diabetes and those who had had a myocardial infarction: cross sectional and cohort studies , 2002, BMJ : British Medical Journal.

[59]  M. Schambelan,et al.  Indinavir acutely inhibits insulin-stimulated glucose disposal in humans: A randomized, placebo-controlled study , 2002, AIDS.

[60]  J. Miro,et al.  Severe nucleoside-associated lactic acidosis in human immunodeficiency virus-infected patients: report of 12 cases and review of the literature. , 2002, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[61]  P. Reiss,et al.  Lipodystrophy in HIV-1-positive patients is associated with insulin resistance in multiple metabolic pathways , 2001, AIDS.

[62]  J. Muller,et al.  Impact of diabetes on long-term survival after acute myocardial infarction: comparability of risk with prior myocardial infarction. , 2001, Diabetes care.

[63]  W C Willett,et al.  The impact of diabetes mellitus on mortality from all causes and coronary heart disease in women: 20 years of follow-up. , 2001, Archives of internal medicine.

[64]  J. Manson,et al.  Diabetes and all-cause and coronary heart disease mortality among US male physicians. , 2001, Archives of internal medicine.

[65]  R. D'Agostino,et al.  Metabolic abnormalities and cardiovascular disease risk factors in adults with human immunodeficiency virus infection and lipodystrophy. , 2001, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[66]  J. Mckenney,et al.  Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). , 2001, JAMA.

[67]  S. Yusuf,et al.  Impact of Diabetes on Long-Term Prognosis in Patients With Unstable Angina and Non–Q-Wave Myocardial Infarction: Results of the OASIS (Organization to Assess Strategies for Ischemic Syndromes) Registry , 2000, Circulation.

[68]  T. Kakuda,et al.  Pharmacology of nucleoside and nucleotide reverse transcriptase inhibitor-induced mitochondrial toxicity. , 2000, Clinical therapeutics.

[69]  Teven,et al.  MORTALITY FROM CORONARY HEART DISEASE IN SUBJECTS WITH TYPE 2 DIABETES AND IN NONDIABETIC SUBJECTS WITH AND WITHOUT PRIOR MYOCARDIAL INFARCTION , 2000 .

[70]  D. Cooper,et al.  Pathogenesis of HIV-1-protease inhibitor-associated peripheral lipodystrophy, hyperlipidaemia, and insulin resistance , 1998, The Lancet.

[71]  David A. Cooper,et al.  A syndrome of peripheral lipodystrophy, hyperlipidaemia and insulin resistance in patients receiving HIV protease inhibitors , 1998, AIDS.