Amusa Proposal II

Burden and Outcomes of co-morbid Cardiovascular diseases in HIV-infected Adults

PRINCIPAL INVESTIGATOR: DR. AMUSA G ADENIYI

Cardiology Unit, Department of Internal Medicine, Jos University Teaching

Hospital.

drganiamusa@gmail.com, 08137713270                                                    

CO-INVESTIGATORS:               DR. ONUH A JAMES

                                                           DR UGURU SAMUEL

 

MENTOR:                                 PROF B.N OKEAHIALAM

MENTOR:                                 DR AKANBI MAXWELL

                                                  

                                DATE OF COMMENCEMENT: JANUARY 2017

ABSTRACT

Background:

The Acquired Immune Deficiency syndrome (AIDS) has been described as a global pandemic. The burden is huge in sub-Saharan Africa where it causes a lot of morbidity and mortality mostly in the young and productive age groups1.

Over 20 million deaths globally have been attributed to HIV infection, with 75% of these occurring in sub-Saharan Africa alone2. The magnitude of the problem is now very huge in terms of the attendant economic cost and loss. Communities with high prevalence of the infection bear severe economic hardship and show signs of retardation in human development2. In Nigeria, the current national prevalence rate is 3.2% at the end of 20143. With a population of more than 170 million people, this represents over 10% of the global pandemic in terms of absolute numbers3. Nigeria has the second largest population of HIV infected persons in the world; the North central part of Nigeria where we are located currently has the 2nd highest prevalence in the country3.        

Following the introduction of anti-retroviral therapy (ART) in 1996 and its progressive availability, there has been a gradual decline in morbidity, mortality rate and a change in causes of death in persons infected with HIV4. In the United States, it is estimated that by 2015 more than half of persons living with HIV will be over 50 years of age5.  Even in Africa many patients now live longer because of access to highly subsidized or free drugs provided by Government and various non-Governmental organizations.

However the increasing lifespan brings to pre-eminence other causes of morbidity and mortality particularly cardiovascular diseases. Studies have reported that cardiovascular disease is commoner in HIV+ compared to HIV- populations and accounts for at least 30% of total mortality and is the third leading cause of death in HIV infected persons4-9.    Reasons adduced for this includes the human immunodeficiency virus, antiretroviral therapy and certain predisposing lifestyles like smoking, alchohol abuse and drug abuse. CVD are commoner in HIV+ compare to HIV- persons and due to the increasing availability and use of anti-retroviral therapy, cardiovascular disease is emerging as an important cause of morbidity and mortality HIV infected persons 4-9.

Cardiovascular diseases causes more than 50% increase in all cause mortality among persons living with HIV17. Early and periodic estimation of coronary heart disease risk score and periodic screening with non-invasive investigations such as electrocardiography and echocardiography will help identify at risk patients and prompt early intervention19-10.

A wide range of cardiovascular diseases has been identified in HIV/AIDS patients. The spectrum ranges from myocardial diseases to pericardial, endocardial disease, coronary artery disease, malignancies, vascular disease, cardiac arrhythmias and autonomic dysfunction.8,11-15

There are few local publications available about cardiovascular diseases in HIV infected persons. Those available are mostly from the western world, and hence the need to do more research to combat this emerging epidemic within the HIV/AIDS pandemic.

Patients and Methods:

This study will be in 2 stages. An initial cross- sectional study will recruit 120 adults with HIV

(HAART experienced/naive) over a 6 months period and a follow-up cohort study over a 12 months period.

Relevant history, physical examination (body mass index and detailed cardiovascular examination to identify cardiovascular co-morbidities) and blood specimen (for fasting plasma glucose, lipids, and E/U/Cr,Uric acid) will be obtained from the subjects at baseline and end of follow-up cohort phase. The Framingham risk score will be used to assess CVD risk at baseline and end of follow-up cohort phase. Also each will have electrocardiography and echocardiography at baseline to assess for CVD. Data will be entered into an interviewer administered questionnaire.

The mean FRS, prevalence of CVD risk factors (defined in this study as smoking, obesity, diabetes mellitus, hypertension, hyperuriceamia, chronic kidney disease and hyperlipideamia) and prevalence of co-morbid cardiovascular diseases will be determined in the first stage and end of cohort phase. The cohort stage will involve following up each participant for 12 months and documenting health related outcomes (in this study CVD related hospitalizations, death and increased specific CVD prevalence and FRS) during this period.

Statistical analysis: Data will be entered into and analyzed using the computer program Epi-Info, version 7.2. Continuous variables will be summarized using mean and standard deviation. Categorical variables will be summarized with percentages in each category. Prevalence will be expressed as a proportion with 95% CI.

Student’s t test will be used to determine the relationship between means of two groups while Fisher’s exact test will be used for categorical variables.

The relationship between mean FRS, presence of CVD, HIV stage and use of HAART and hospitalizations/ mortality will be determined using cox proportional hazard models. 

Multivariate logistic regression analysis will be done to determine the associations between mean FRS and CVD and CD4 count and associated factors/predictors of endpoints. Significance will be defined as p value less than 0.05 in all cases.

 

NIH FORM BIOGRAPHICAL SKETCH

 

 

NAME

Amusa Ganiyu Adeniyi

POSITION TITLE

Consultant Physician/ Cardiologist

eRA COMMONS USER NAME (credential, e.g., agency login)

drganiamusa

EDUCATION/TRAINING 

INSTITUTION AND LOCATION

DEGREE

(if applicable)

MM/YY

FIELD OF STUDY

Olabisi Onabanjo University, Ogun State Nigeria. Nigeria

MBChB

05/2004

Medicine & Surgery

 

 

 

 

National Postgraduate Medical College of Nigeria. Nigeria

FMCP

11/2013

Internal Medicine (Cardiology)

 

 

 

 

West African College of Physicians. Ibadan Nigeria.

FWACP

04/2014

Internal Medicine (Cardiology)
         

A.        Personal Statement

I am a Physician, who has worked in different levels of the Nigeria health care system over the last 12 years and is currently a consultant Physician/Cardiologist at the Jos University Teaching Hospital, Jos; Nigeria. My research interests include the estimation of the burden of cardiovascular disease in sub-Saharan Africa, cardiovascular co-morbidities in chronic diseases as HIV/AIDS, Diabetes, COPD e.t.c. emergency medicine, critical care and translational medicine.

I have completed and passed two dissertations (Cardiovascular Abnormalities in HIV-infected Adults in JUTH and Left Ventricular dysfunction in type2 diabetics in JUTH).

I have a strong passion for research and have participated in several international studies with my mentors as a Research Physician in the Jos University Teaching Hospital site for the REMEDY and RhGEN studies (on Rheumatic Heart Diseases) and co-PI for the INVICTUS study. I am also a co-PI for the SIREN study JUTH site and is currently the PI for the Burden and Outcomes of co-morbid Cardiovascular diseases in COPD (a MEPIN funded study which I just rounded up).

It is on the basis of learning from senior researchers and my last study ‘Cardiovascular Abnormalities in HIV-infected Adults in JUTH that have prepared me to lead this present proposed study.    

Research Activities (Ongoing)

  1. Global Registry on Rheumatic Heart Disease (REMEDY Study), JUTH centre. (Research Physician).
  2. Rheumatic Heart Disease Genetic Study (RhGEN Study), JUTH centre. (Research Physician).
  3. Burden and Outcomes of co-morbid Cardiovascular diseases in COPD in North-Central Nigeria. (Primary Investigator, MEPIN Year 05 Mentored Research Grant Award).
  4. Stroke Investigative Research and Education Network (SIREN) Study. (Member, Cardiology Working Group)
  5. Profile of Stroke Patients in JUTH. (STAMINA Research Grant Award, Research Team Member).
  6. Neuropsychiatric manifestations of SLE: A 5 year prospective study. (Research Team Member).

B.        Positions and Honors

Positions & Employment

July 04 - July 05

House Officer, Olabibisi Onabanjo University Teaching Hospital, Sagamu, Nigeria

 

Oct 05 - Aug 06

Medical Officer- National Youth Service Corp. Langtang South LGA Health Department, Plateau State,  Nigeria

Sept 06 - Feb 14

Medical Residency, Internal Medicine, Jos University Teaching Hospital Plateau State Nigeria

Feb 14 - April 14

Consultant Physician/Cardiologist, Federal Medical Center, Keffi, Nasarawa State

 

April 14 - Present

Consultant Physician/ cardiologist, Jos University Teaching Hospital, Plateau State Nigeria

 

Community services

        1. Vice President, Association of Resident Doctors, JUTH.               2010 – 2011.

        2. Editor-In-Chief, Jos Journal of Medicine.                                      2011 – 2013.

        3. Assistant Secretary General, MDCAN, JUTH.                              2014 –

        4. Visiting Consultant Cardiologist, Faith Alive Foundation.              2014 –

        5. Visiting Consultant Cardiologist, Heart Aid Foundation.                2014 –

        6. Chairman, Audit Committee, NMA Plateau.                                  2015-

Honors

  1. NYSC Plateau State Certificate of Merit Award (Governor’s Award), August 2006.
  2. PATS-MECOR Travel Grant Awards to attend PATS-MECOR Conferences in Kenya (2012, 2013, and 2014).
  3. ATS-MECOR Travel Grant Award to attend ATS International Scientific Conference in Denver, Colorado (May, 2014).
  4. University of Jos, MEPIN Research Grant Award (May, 2015)
  5. ATS Travel Grant Award to attend ATS Global MECOR Conference in Istanbul, Turkey (November, 2015). 
  6. ISH Travel Grant Award to attend ISH International Scientific Conference in Seoul, South Korea (September 2016).                                              

C.        Publications

            (a) Selected Articles in Journals

  1. Odili A.N., Amusa G.A. Aortic aneurysm with valvular insufficiency: Is it due to marfan’s syndrome or hypertension? A case report and review of literature. (2011) J Vasc Nurs. 29(1):16-22.
  2. Ukoli C.O., Akanbi M.O., Adiukwu C.V., Amusa G.A., Akanbi F.O. (2012). Diagnosing Tuberculosis in Resource Limited Settings: Experience from a Referral TB Clinic in North-Central Nigeria. Jos Journal of Medicine. 6(1):27-28.
  3. Amusa G.A. Cardiovascular disease: A Global Epidemic extending into Africa. (2012). Jos Journal of Medicine. 6(2):6-12.
  4. Alison Lee, Amusa G.A., et al. (2015). Household air pollution: A call to action. The Lancet Respiratory Medicine. 3:e1-e2.
  5. C.M., Chundusu. G.A., Amusa. Danbauchi S.S., Okeahialam B.N. et al. (2015)  Descriptive evaluation of holter recordings at a teaching hospital in central Nigeria. (2015). Highland Med Res J. 15(2):59-62.
  6. Uguru S.U., Amusa G.A., Okeahialam B.N. et al. (2015) Idiopathic Calcific Constrictive Pericarditis: An Unsettling Reality. Jos Journal of Medicine. 2015;9(3):37-40.

          (b) Selected Papers presented at Conferences

  1. Amusa G.A. Odili A.N. (2008). Marfan’s Syndrome: A case report presented at The Nigerian Cardiac Society 37th AGM and Scientific Conference, Jos, Plateau state.
  2. Amusa G.A., Danbauchi S.S., Okeahialam B.N., et al. (2015). Cardiovascular Disease Risk Factors in HIV-infected Adult Patients in North-Central Nigeria; (Poster Presentation). ATS International Scientific Conference, Denver, Colorado, USA; May 2015.
  3. Amusa G.A., Danbauchi S.S., Okeahialam B.N., et al. (2016). Electrocardiographic Abnormalities in HIV-infected Adult Patients in North-Central Nigeria; (Accepted for Poster Presentation). ATS International Scientific Conference, San Francisco, California, USA; May 2016.
  4. Amusa G.A., Danbauchi S.S., Okeahialam B.N.,  et al. (2016). Echocardiographic Abnormalities in HIV-infected Adult Patients in North-Central Nigeria; (Accepted for Poster Presentation). ATS International Scientific Conference, San Francisco, California, USA; May 2016.
  5. Amusa G.A., Danbauchi S.S., Okeahialam B.N.,  et al. (2016). Left Ventricular Dysfunction in Asymptomatic Hypertensive Patients with and without Type 2 Diabetes: Prevalence, Patterns and Associated Factors. (Accepted for Poster Presentation). ISH International Scientific Conference, Seoul, South Korea. September 2016.
  6. Amusa G.A., Danbauchi S.S., Okeahialam B.N.,  et al. (2016). Hypertension in HIV infected Adults in North Central Nigeria: Prevalence, Associated Risk factors and Assessment of Risk using the Framingham Risk Score (Accepted for Oral Presentation). ISH International Scientific Conference, Seoul, South Korea. September 2016.

 D.       Research Support

  1. University of Jos, MEPIN Research Grant Award (May, 2015)

BUDGET

 

PROPOSED BUDGET FOR THE STUDY:

ITEM                            QUANTITY   FREQUENCY    UNIT COST(N)  TOTAL COST(N)

 Personnel:

  Research Assistant                   1             18 months             10,000                  180,000

Materials and supplies:

  Sample bottles                       140           2/ Subject                100                     28,000       

  Syringes and needles            140           2/ Subject                20                        5,600        

Papers                                       4rims                                       2000                    8000

Laboratory Investigations:

  Lipid profile assay                120           2/ Subject              1,500                   360,000

  Fasting blood sugar               120           2/ Subject              200                     48,000

Serum U/Cr/Uric acid          120           2/ Subject                2000                    480,000

 

Radiology:

  Electrocardiography              120                                          1000                 120,000

  Echocardiography                 120                                           5600                672,000 

Phone calls                                                                                                       18,400   

Statistician Fee                                                                                                40,000

Publication in Journal                                                                                    40,000

 

GRAND TOTAL                                                                                            2,000,000

 

GRAND TOTAL= N2,00,000 (TWO MILLION NAIRA ONLY)

BUDGET JUSTIFICATION

Principal Investigator: Amusa Ganiyu Adeniyi

Project title: Burden and Outcomes of co-morbid Cardiovascular diseases in HIV-infected Adults.

Personnel:

Mentors (Prof B.N Okeahialam): Will provide scientific support and supervision throughout the duration of the research. No salary requested.

Mentor (Dr Akanbi Maxwell Oluwole): Will provide statistical support throughout the duration of the research. No salary requested.

Dr Amusa G Adeniyi: Will oversees all aspects of the research - protocol design, recruitment, data collection, analysis and interpretation of results. No salary requested

Co- Investigators (Dr Onuh James, Dr Uguru Samuel): Will be involved in recruitment, data collection, analysis and interpretation of results. No salary requested.

Statistician: Will analyze the data gathered during the research.

Research Assistant: Will coordinate research logistics, patient recruitment, data collection and laboratory investigations.

Others:  

Universal bottles: These will be used to collect the blood samples for fasting sugar and lipid profile.

Syringe and needles: These will be used to collect venous blood from the participants.

CD4 Count: Will be related to specific Cardiovascular diseases

Lipid profile assay: This will determine the presence of abnormal cholesterol and triglyceride levels for the participants, a risk factor for cardiovascular disease

Fasting blood sugar assay: This will determine the presence of hyperglycemia, another risk factor for cardiovascular disease

E/U/Cr/UA- This will determine the presence of hyperuricaemia and CKD, another risk factor for cardiovascular disease

Electrocardiography: This will enable diagnosis of atrial fibrillation, ischeamic heart diseases cardiomegaly e.t.c

Echocardiography: This will enable diagnosis of heart diseases such as heart failure, cardiomyopathy, ischeamic heart diseases, cor-pulmonale e.t.c.

Publication costs: Research findings will be published in a peer- reviewed journal.

PROJECT NARRATIVE

The availability of funds to conduct this research will provide information about the prevalence of co-morbid cardiovascular diseases and outcomes in adults with HIV/AIDS. This would serve as a basis for future research on early detection and management of these co-morbidities which has been shown to occur and is associated with increased morbidity and mortality.

RESEARCH PLAN

Specific aims:

  1. To determine the prevalence of specific cardiovascular disease risk factors in the subjects.
  2. To determine the 10 year predicted coronary heart disease risk score from the risk factors obtained using the Framingham’s risk score in the subjects.
  3. To determine the prevalence of specific cardiovascular diseases (electrocardiographic/echocardiographic abnormalities) found in HIV infected persons.
  4. To evaluate the relationship between CD4 count and duration of antiretroviral therapy use to health related outcomes (hospitalizations, mortality, FRS, prevalence of specific cardiovascular disease) in adults with HF over a period of 12 months.

BACKGROUND AND SIGNIFICANCE

The Acquired Immune Deficiency syndrome (AIDS) has been described as a global pandemic. The burden is huge in sub-Saharan Africa where it causes a lot of morbidity and mortality mostly in the young and productive age groups1.

The magnitude of the problem is now very huge in terms of the attendant economic cost and loss. Communities with high prevalence of the infection bear severe economic hardship and show signs of retardation in human development2. In Nigeria, the current national prevalence rate is 3.2% at the end of 20143. With a population of more than 170 million people, this represents over 10% of the global pandemic in terms of absolute numbers3. Nigeria has the second largest population of HIV infected persons in the world; the North central part of Nigeria where we are located currently has the 2nd highest prevalence in the country3.        

Following the introduction of anti-retroviral therapy (ART) in 1996 and its progressive availability, there has been a gradual decline in morbidity, mortality rate and a change in causes of death in persons infected with HIV4. In the United States, it is estimated that by 2015 more than half of persons living with HIV will be over 50 years of age5.  Even in Africa many patients now live longer because of access to highly subsidized or free drugs provided by Government and various non-Governmental organizations.

However the increasing lifespan brings to pre-eminence other causes of morbidity and mortality particularly cardiovascular diseases. Studies have reported that cardiovascular disease is commoner in HIV+ compared to HIV- populations and accounts for at least 30% of total mortality and is the third leading cause of death in HIV infected persons4-9.  Reasons adduced for this includes the human immunodeficiency virus, antiretroviral therapy and certain predisposing lifestyles like smoking, alchohol abuse and drug abuse.  Due to the increasing availability and use of anti-retroviral therapy, cardiovascular disease is emerging as an important cause of morbidity and mortality HIV infected persons 4-9.

Cardiovascular diseases causes more than 50% increase in all cause mortality among persons living with HIV17. Early and periodic estimation of coronary heart disease risk score and periodic screening with non-invasive investigations such as electrocardiography and echocardiography will help identify at risk patients and prompt early intervention19-10.

A wide range of cardiovascular diseases has been identified in HIV/AIDS patients. The spectrum ranges from myocardial diseases to pericardial, endocardial disease, coronary artery disease, malignancies, vascular disease, cardiac arrhythmias and autonomic dysfunction.8,11-15

There are few local publications available about cardiovascular diseases in HIV infected persons. Those available are mostly from the western world, and hence the need to do more research to combat this emerging epidemic within the HIV/AIDS pandemic.

EXPERIMENTAL DESIGN AND METHODS

This will be a multi-staged study with an initial cross-sectional descriptive stage and a latter follow-up cohort stage. Subjects will be recruited from the ART clinic of Jos University Teaching Hospital (JUTH) in Jos, Plateau state. The laboratory investigations will be carried out at the chemical pathology laboratory of JUTH. Similarly the electrocardiography and echocardiography will be carried out at JUTH.

Study subjects:

Consecutive consenting adult patients who have tested positive to HIV and are not acutely ill will be recruited into the study. Informed consent will be obtained from each participant. 

Sample size determination:

The minimum sample size was determined using the formula below:

n = (Z) 2(1-P)(P)

              d 2

Where:

n = minimum sample size

Z = 95% confidence interval = 1.96

P = prevalence of cardiovascular diseases in HIV infected adults in Nigeria is unknown, 50% will be used

d = precision (absolute error), set at 10% = 0.1

n = (1.96 )2  (1- 0.5) (0.5)

                        (0.1)2

n = 96

This will be rounded up to 120 adults with HIV infection.

Data collection:

Relevant history, physical examination (body mass index and detailed cardiovascular examination to identify cardiovascular co-morbidities) and blood specimen (for fasting plasma glucose, lipids, E/U/Cr, Uric acid and CD4 count) will be obtained from the subjects. Also each will have electrocardiography and echocardiography (to diagnose cardiovascular diseases) done and data filled into an interviewer administered questionnaire. The prevalence of co-morbid cardiovascular diseases and associated risk factors (defined in this study as smoking, obesity, diabetes mellitus, hypertension, hyperuriceamia, chronic kidney disease and hyperlipideamia) will be determined in the first stage. The FRS for each participant will be assessed also. The cohort stage will involve following up each participant for 12 months and documenting health related outcomes (in this study cardiovascular related hospitalizations and death) during this period.

Ethical Consideration: Ethical clearance will be obtained from the research and ethics committee of the Jos University Teaching Hospital before the study is commenced. Informed consent will be obtained from the participants.

Statistical analysis: An initial one way analysis will be conducted to assess the distribution for each variable. Continuous variables will be summarized using mean and standard deviation. Categorical variables will be summarized with percentages in each category. Prevalence will be expressed as a proportion with 95% CI.

Student’s t test will be used to determine the relationship between means of two groups while Fisher’s exact test will be used for categorical variables.

The relationship between FRS, Specific Cardiovascular diseases, HIV parameters (duration of ART, Viral load and CD4 count) and hospitalizations and mortality will be determined using cox proportional hazard models. 

Multivariate logistic regression analysis will be done to determine the associations between FRS, specific cardiovascular diseases and HIV parameters. Significance will be defined as p value less than 0.05.                                                      

                        

REFERENCES

  1. The Joint United Nations, Programme on HIV/AIDS (UNAIDS) and World Health Organization (WHO). AIDS epidemic update, 2009 report.
  2. UNDP-Human Development Report Geneva WHO 2005.
  3. Federal Ministry of Health. National HIV Sero-prevalence Sentinel Survey. Abuja. Federal ministry of Health, 2016.
  4. Palella FJ, Delaney KM, Moorman AC, Loveless MO, Furher J, Satten GA et al. Declining morbidity and mortality among patient with advanced HIV infection, N Engl J Med 1998; 338: 853-860.
  5. Effros RB, Fletcher CV, Gebo K, Halter JB, Hazzard WR, Home FM. Aging and Infectious diseases: workshop on HIV infection and aging: what is known and future research directions. Clin Infect Dis.2008; 47:542-553.
  6. Muralikrishna G, Archana B, Wissam I K, and Alejandro B. Heart Disease in Patients with HIV/AIDS-An Emerging Clinical Problem. Curr Cardiol Rev. 2009 May; 5(2): 149–154.
  7. Cammarosano C, Lewis W. Cardiac lesions in acquired immune deficiency syndrome (AIDS). J Am Coll Cardiol. 1985; 5:703.
  8. Babaro G. Cardiovascular manifestations of HIV infection. JR Soc Med 2001:94:384-390.
  9. Friis-Moller N, Weber R, Riess P, Thiebaut R, Kirk O, d’Arminio MA, et al. Cardiovascular disease risk factors in HIV patients-association with antiretroviral therapy. Results from the D.A.D study. AIDS 2003, 17(8): 1179-1193.
  10. Dzau VJ, Antman EM, Black HR, Hayes DL, Manson JE, Plutzky J et al. The Cardiovascular disease continuum validated: clinical evidence of improved patient outcomes: part 1: pathophysiology and clinical trial evidence. Circulation 2006; 114:2850-2870.
  11. Okeahialam BN, Anjorin FL. Echocardiographic study of the heart in AIDS. The Jos experience. Trop Card 2000; 26:3-6.
  12. Danbauchi SS, Sani SG, Alhassan MA et al. Cardiac manifestations of stage III/IV HIV/AIDS compared to subjects on ARV in Zaria, Nigeria. Nig J Cardiol 2006; 3:5-10.
  13. Olusegun-Joseph DA, Ajuluchukwu JN, Okany CC, Mbakwem AC, Oke DA, Okubadejo NV. Echocardiographic patterns in treatment naïve HIV-positive patients in Lagos, south west Nigeria. Cardiovasc J Afri 2012; 23(8): e1-6.
  14. Okeahilam B.N, Babashani M.B. Infective Endocarditis in AIDS. Trop Card.2001; 27(108):68-69.
  15. Sani MU, Okeahialam BN. QTc interval prolongation in patients with HIV and AIDS. J Natl Med Assoc. 2004; 97(12): 1657-1661.

PLAN FOR PROTECTION OF HUMAN SUBJECTS

The study will involve minimal risk to the participants. Participants found to have co-morbid cardiovascular diseases will be managed appropriately. The study will also be beneficial to HIV infected adults with cardiovascular disease that will be managed in the future. Written and informed consent will be obtained from the participants. Information obtained will be safeguarded by entering data without identifiers while the questionnaires will be kept locked up until two years after completion of the study.

IRB APPROVAL

Ethical clearance will be obtained from the JUTH Human Research Ethics Committee for the study.