Imoh Proposal

Running Heading: Subclinical Atherosclerosis and CVD risk Factors in HIV

The Prevalence of Subclinical Atherosclerosis and Cardiovascular Risk Factors Among HIV Infected Individuals in Jos.

Dr Imoh Lucius Chidiebere

Department of Chemical Pathology

Jos University Teaching Hospital

 

ABSTRACT

Background: Cardiovascular disease (CVD) is the leading cause of death and morbidity globally. Atherosclerosis is a fundamental vascular disease process underlying the development or progression to CVDs. HIV/AIDS is fast gaining reputation as a leading cause of CVDs in sub-haran Africa. The burden of HIV/AIDS remains high in sub-Saharan Africa (SSA) and Nigeria is among the countries with the highest prevalence. Yet there are no established strategies for screening or preventing CVDs in many SSA countries. The burden of cardiovascular disease in People living with HIV (PLWH) is Nigerian population is not well-known.Little is known about the correlation between the traditional CVD risk factors or the various population-based CVD risk prediction algorithms with the presence of CVD endpoint like subclinical atherosclerosis.

Objectives:To determine the the prevalence of subclinical atherosclerosis and its association with cardiovascular disease risk factors and prediction models among HIV Infected individuals in a Nigerian hospital setting.

 

Method: This will be a cross-sectional comparative study to be carried out at the APIN-supported HIV clinics at Jos University Teaching Hospital (JUTH) and Faith Alive Foundation (FAF) over a period of two years. Consecutive HIV patients who satisfy the inclusion criteria and gives consent will be recruited into the study. Apparently healthy HIV negative controls who meets the inclusion and matching criteria will also be studied.

 

Socio-demographic data, cardiovascular risks factors, relevant present and past medical history will be assessed. Information regarding HIV related factors shall be obtained from patients records. Biophysical and anthropometric measurement, Carotid Intimal Media Thickness, and relevant laboratory parameters (Fasting Lipid profile, Fasting Plasma Glucose, CD4 Count, Viral Load) will be studied and Cardiovascular risk prediction Models including: 10-year Framingham CVD risk score; 5-year DAD risk estimation; Prospective Cardiovascular Munster study (PROCAM) and Systematic Coronary Risk Evaluation (SCORE) will be computed.

 

Data will be analyzed with the Statistical Package for Social Sciences (SPSS® Incorporated Chicago Version 18.0) software. Frequency tables will be generated for the variables of interest. Descriptive statistics will be presented as mean values + standard deviation (SD) or medians with interquartile ranges (IQRs) for non-normal continuous variables, and proportions (as percentages) for categorical variables. Unpaired students t-test or Mann-whitney U test will be used to test the difference in means or medians of continuous variables between groups. Bivariate analysis and multivariate logistic regression will be used to examine the relationship between CVD risk factors or CVD risk prediction models and subclinical atherosclerosis. Difference in proportions of subclinical atherosclerosis in cases and control groups will be tested using Z-test. A p value of < 0.05 will be taken as a measure of statistical significance.

 

BIOGRAPHICAL SKETCH

 OF PRINCIPAL INVESTIGATOR

NAME: Imoh Lucius Chidiebere

 

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

 

POSITION TITLE: Consultant Chemical Pathologists/Metabolic physician

 

EDUCATION/TRAINING

INSTITUTION AND LOCATION

DEGREE

 

Completion Date

MM/YYYY

 

FIELD OF STUDY

 

NnamdiAzikiwe University, Anambra State

MBBS

June 2005

Medicine and Surgery

Cardiff University

Diploma

June 2013

Medical Toxicology

Jos University Teaching Hospital, Plateau State

FMCpath

Oct 2013

Chemical Pathology

 

 

 

 

 

 

 

 

A.        PERSONAL STATEMENT

The goal of this research is to determine the prevalence of subclinical atherosclerosis and to assess the underlying risk factors in HIV-infected individuals in two HIV treatment centres in Jos. I have spent a good part of the six years as a resident doctor and now as a consultant chemical pathologists and metabolic physician in managing both metabolic and laboratory aspects of HIV patients’ care. During this time, I haveincreasingly noticed the presence of one or more traditional risk factors for CVDs in HIV patients. However, it is not clear if the presence of these risk factors actually translate to vascular disease and subsequently CVDs. I have also noticed gaps in risk assessment for CVDs among HIV-patients evidence by lack of national policy for routine CVDs risk assessment. This is study is designed to provide data to fill the knowledge gap in our understanding of risk assessment for CVDs in Nigerian PLWH. I am confident that my experience in metabolic medicine and HIV treatment and care research has equipped me with the necessary expertise and motivation to successfully execute this research project.

  1. Ikechebelu IJ, Udigwe GO, Ikechebelu N, Imoh LC. The Knowledge, Attitude And Practice of Voluntary Counselling and Testing (VCT) For HIV/AIDS Among Undergraduates in A Polytechnic in Southeast, Nigeria. Niger J Med. 2006 Jul-Sep;15(3):245-9
  2. Imoh  LC, Inaku KO, Abu A and Amadu NO. Lipid Profile and Insulin Resistance in Pregnant Women with Family History of Diabetes Mellitus. Jos Journal of Medicine. 2014; 8(1): 19-22
  3. Imoh LC, Ocheke AN. Correlation between Maternal Weight and Insulin Resistance in Pregnant Women in North Central Nigeria. Nigerian Medical Journal. Nov 2014; 55(6):465-468
  4. Imoh LC, Amadu NO, Abu A and Asorose SA. Appraisal of timing for Oral Glucose Tolerance Testing in relation to risk factors for Gestational Diabetes Mellitus in pregnant women in a Nigerian Teaching Hospital. Nigerian Journal of Clinical Practice. Nov-Dec 2015;18(6): 771-4
  5. Isichei, C.O., Isichei, M.W., Njab, J.E., Rotimi, J.I., Oyebode, T.A., Anyaka, C.U., Enwerem, K.E., Affi, A.I., Imoh, L.C., Abu, A.O., Asorose, S.A., Amadu, N.O., Okonkwo, P.I. and Okoro, N.I. Baseline Laboratory Profile of HIV Positive Patients on Antiretroviral Therapy in Jos North Central Nigeria: Implications for Prevention, Treatment, Care and Support. World Journal of AIDS. 2015; 5: 328-334. http://dx.doi.org/10.4236/wja.2015.54036
  6. Imoh LC, Ogunkeye OO, Isichei CO, Gadzama AA, John C, Ocheke AN. Severe maternal insulin resistance in pregnancy: An independent predictor of fetal macrosomia. J Med Trop [Epub ahead of print] [cited 2016 Oct 6]. Available from: http://www.jmedtropics.org/preprintarticle.asp?id=188531                                                       

B.        POSITIONS AND HONORS

Positions and Employments

2009 – 2011 – Registrar, Chemical Pathology

2011-2013 – Senior Registrar and Chief Resident, Department of Chemical Pathology, JUTH

2013 – Fellow, National Postgraduate Medical College of Nigeria, Consultant Chemical Pathologist, JUTH

2014 – to date- Assistant Secretary, College of Nigerian Pathologists, JUTH CHAPTER

2014 to date- Public Relations Officer, Christian Medical and Dental Association, Plateau State

September 2016 to date - Secretary, Christian Medical and Dental Association, Plateau State

Other Experience and Professional Memberships

2005- Member, Nigeria Medical Association

2005 -Member, Medical and Dental Council of Nigeria

2013- Fellow, National Postgraduate Medical College of Nigeria

2013- Member Medical and Dental Consultants of Nigeria

2014- Member, College of Nigerian Pathologists (CNP), formerly Association of Pathologists of Nigeria (ASSOPON)

2014- Member Association of Clinical Chemists of Nigeria

Honors

1997- Best Graduating Student Newland Secondary School Tolu, Lagos

2005- 3rd Best Graduating Student, College of Health Science, NnamdiAzikiwe University, 2005

2013- Distinction in Medical Toxicology (Cardiff)

2013-Best Candidate in Part II Examination (Chemical Pathology), National Postgraduate Medical College of Nigeria

 

 

BREAKDOWN OF BUDGET FOR THE STUDY

  1. Laboratory Tests/ Carotid Doppler Ultrasound – 1,905,000 NAIRA
  2. Data Collection / Analysis – 100,000 NAIRA
  3. Research Assistant – 100,000 NAIRA
  4. Laboratory Technician- 60,000 NAIRA
  5. Total – 2,165,000 NAIRA

 

BREAKDOWN OF THE BUDGET FOR THE TESTS

 

Serial No.

Item/Test

Unit Cost (Naira)

Quantity

Total Cost (Naira)

1

Fasting Lipid profile

2500

360

900,000

2

Fasting Plasma Glucose

500

360

180,000

3

Carotid Doppler Ultrasound

2000

360

720,000

4

CD4 Count

APIN/FAF Database

5

Viral Load

APIN/FAF Database

 

 

 

 

 

 

Consumables

 

 

 

6

SST

2000

8

16,000

7

Cryovast

30

1000

30,000

8

Pastuer pipette

25

1000

25,000

9

Vacutainer needles

20

1000

20,000

10

Gloves

1000

5 packs

5,000

11

Cotton wool

1500

2 packs

3000

12

Methylated Spirit

1500

2bottles

3000

13

5mls Syringe

1500

2 packs

3000

Total

 

 

 

1,905,000

 

BUDGET JUSTIFICATION         

1.  Data collection and analysis

  • Printing of Questionnaire
  • Data Management and analysis by statistician

2. Research Assistant – would be involved in educating participants, administering the questionnaire, and taking anthropometric measurements and collecting blood samples

3. Laboratory Technician – Will help to process samples for biochemical analysis.

 

PROJECT NARRATIVE

This award will help fund the documentation of the prevalence of subclinical atherosclerosis and its correlations with cardiovascular disease risk factors and prediction models among HIV-infected individuals in a Nigerian hospital setting. Data from this initial study will provide baseline information on cardiovascular risk among Nigerians PLWH and help source for funding for future research work that will focus on understanding the role of non-traditional cardiovascular risk in atherosclerosis and CVDs among PLWH as well as developing models to assess and predict CVD risk in Nigerian populations.

RESEARCH PLAN

GENERAL AIM

To determine the the prevalence of subclinical atherosclerosis and its association with cardiovascular disease risk factors and prediction models among HIV Infected individuals in a Nigerian hospital setting in Jos University Teaching Hospital

SPECIFIC AIMS

  1. To determine prevalence of subclinical atherosclerosis in HIV Infected individuals and healthy non- HIV-infected controls
  2. To determine the significant predictors of subclinical atherosclerosis in HIV Infected individuals and healthy non- HIV-infected controls
  3. Assess the CVDs prediction models based on their correlation/association with CIMT/ subclinical atherosclerosis in HIV Infected individuals and healthy non- HIV-infected controls

BACKGROUND AND SIGNIFICANCE

Cardiovascular disease (CVD) is the leading cause of death and morbidity globally.1,2 CVD is a generic term for a group of diseases of the heart and vascular diseases including of the brain and peripheral circulation. It includes diseases such as Ischaemic heart disease, cerebrovascular disease (e.g. stroke), peripheral arterial disease, rheumatic heart disease, congenital heart disease, deep vein thrombosis and pulmonary embolism, cardiomyopathy and cardiac arrthymias.3

 

Globally, CVDs are responsible for more than 17.5million deaths annually, nearly half of all deaths caused by Non communicable diseases (NCD) and nearly 80% of those who die annually from CVDs and diabetes mellitus (DM) live in resource limited settings.3,4,5 There is therefore growing apprehension about rising incidence mortalities from CVDs in the low and middle income countries.1,6 The rapid epidemiological transition in the burden of diseases from communicable to Non communicable diseases (NCDs) like hypertension, DM and their related complications in sub-haran Africa (SSA) is well documented and this is anticipated to increases the incidence and mortality of CVDs.1 This trend has been attributed to urbanization and a drift towards westernized lifestyle.7

Atherosclerosis is a fundamental vascular disease underlying the development or progression to CVDs.3 It involves a complex pathophysiologic process resulting in deposition of fatty materials, thickening of the intima and narrowing of blood vessels. The combination of endothelial dysfunction, chronic inflammation and dyslipidemias are central to the pathogenesis of atherosclerosis.8 These processes are often present in conditions of interrelated metabolic disorders including insulin resistance, obesity, impaired glucose tolerance and hypertension which are known to heighten cardiovascular disease risk. This association is widely regarded as as cardiometabolic syndrome.9

HIV/AIDS is fast gaining reputation as a leading cause of CVDs in SSA.10,11 In addition to the usual risk factors for CVDs in the general populations, People Living With HIV (PLWH) may possess addition risk factors related to endothelial dysfunction, metabolic effects of antiretroviral drugs (dyslipidemias, Insulin resistance) and the chronic inflammation induced by Human Immunodeficiency Virus (HIV) which heightens their predisposition to CVDs.7,12

The burden of HIV/AIDS remains high in SSA and Nigeria is among the countries with the highest prevalence with about 3.5 million people infected with HIV.13Although there appear to be some success regarding the prevention of new infections and increasing survival of AIDs- related deaths due to treatment of with Antiretroviral Therapy (ART), a new kind of challenge in the rising incidence of NCDs especially CVDs in PLWH is emerging.7 The high burden of HIV in Nigeria coupled with the increasing life expectancy of PLWH due to treatment with ARTs is setting the stage for a likely increased incidence of NCDs and CVDs among PLWA in Nigeria. Understandably, there are concern that the rising CVDs burden could mitigate or even reverse the improvement in morbidity and life expectancy being recorded among PLWH.7

In view of the foregoing, research on HIV/AIDs is beginning to focus on the risk factors and their role in development of CVDs and other NCDs. However, data on CVDs among PLWH in SSA countries remain sparse. Most of the studies to understand the burden and mechanism of CVDs in HIV has been in carried out among populations of high income countries who usually have a different risk profile to that of people of Nigerian and African ancestry. The few studies in Nigeria have investigated the presence of risk factors of CVDs without relating them to cardiovascular endpoints therefore it is not clear if these risk factors are actually associated with vascular changes suggesting  vascular diseases or a high risk of progression to CVDs.14-16

The presence of Subclinical Atherosclerosis which can determine by Carotid Intimal Medial Thickness (CIMT) is a harbinger for CVDs.17-19 CIMT is a well validated surrogate imaging marker for cardiovascular assessment and future cardiovascular morbidity and mortality risk.19-25 It does appear that there is population based significance of CIMT in HIV infected subject.18,26,27 This may be related to varying socio-demographic, genetic factors and the profile of traditional risk factors across populations.18,20 The two Previous studies on Subclinical atherosclerosis among PLWH in SSA (Uganda and south Africa) where limited by a lack of an HIV-negative control group which made it impossible to draw any conclusions on the true effect of HIV infection on CIMT.18,20 Also the cut-off CIMT used to demarcate Subclinical atherosclerosis in these studies were not obtained from the local population, and this may have influenced their findings.

We do not know what proportions of PLWH have subclinical atherosclerosis and if this is related to the traditional cardiovascular risk factors of CVDs. Indeed it has been suggested that mean CIMT is elevated even among normal Nigerians.28 It is not clear how the CIMT in Nigerian PWLH compares with that of the non-diabetic, non-hypertensive, HIV negative individuals.

Risk factor assessment and management have been the cornerstones of preventive strategies. Although CVDs risk prediction models have been used for decades to prevent CVDs in both HIV and non HIV patients,24,29 there are no established strategy for screening or preventing CVDs in many SSA countries.18 Also Cardiovascular screening and prevention are currently not part of routine HIV care in Nigeria. This may be due to a lack of evidence of the predictive ability of any of the CVDs in Nigerian populations.

Recent data suggest prediction for cardiovascular disease among PLWH may not been very accurate with established CVDs risk prediction models like the Framingham Risk score and the Systematic Coronary Risk Evaluation (SCORE).25,26,30 A case for the use of the 5-year Data Collection on Adverse Effects on Anti-HIV Drugs Cohort (D.A.D) has been made in a number of studies.25 However, the performance of the various risk scoring models has not been well studied in Nigerian populations.

This study therefore is attempting to fill these gaps in our understanding of CVDs among PLWH. The prevalence of subclinical atherosclerosis will be determined and this will provide the much need baseline information that will help to predict the burden of CVD among PLWH in Nigeria. The CVDs risk prediction models will be assessed in the light of the presence of Subclinical atherosclerosis. Although prediction models were designed to forecast future CVDs, a robust predictive model is expected to correlate well with the existence of vascular disease in the present even if subclinical. It is hoped that this study will reveal any peculiarities in CVDs assessment among Nigerian PLWH.

EXPERIMENTAL DESIGN AND METHODS 

This is a comparative cross sectional study to determine the prevalence of subclinical atherosclerosis in HIV Infected individuals and normal healthy controls and to assess how cardiovascular disease risk factors and prediction models correlates with subclinical atherosclerosis in HIV Infected individuals and normal healthy controls.

SAMPLE SIZE DETERMINATION

The sample size was determined by the formula for chi square test comparing 2 independent proportions.

The sample size was estimated using the formula; 

n = {P1 (1-P1) + P2 (1-P2)} X (Z α +Z β)2

                        (P1-P2)2

Where:

n: number of sample size in each of the group

P1= proportion of subclinical Atherosclerosis among cases (0.18 in the Ugandan study).20

P2= Assumed proportion of subclinical Atherosclerosis among controls = 0.06 (Assumed ratio of Case : Control = 3:1)

Z-α/2= value of standard normal distribution corresponding to a significance level of alpha (1.96 for two-sided test at the 0.05)

Z-β/2=value of standard normal distribution corresponding to the desired level of power (0.84 for a power of 80%)

n = {(0.18×0.82 + (0.06 × 0.94)} x (1.96 + 0.84)2

                             (0.12)2

n≈ 114

This was confirmed using statistical software STATA version 13.

The sample size was adjusted to 120 for the cases (120 ART-treated subjects) and 120 for (120 HIV-negative apparently healthy controls) to compensate for an attrition rate of 5%. 

Study Area

This will be a cross sectional comparative study to be carried out at the AIDS Prevention Initiative in Nigeria (APIN)-supported HIV clinic at the Jos University Teaching Hospital (JUTH). The JUTH HIV clinic is located in the urban city of Jos, plateau state. It serves a population of over 22 million people from Plateau and the neighboring north central states of Nigeria. The clinic commenced HIV services in 2002, and has cumulatively enrolled over 17,000 adults for HIV care and treatment; with over 10,000 on follow up31.

Faith Alive Foundation is a non-governmental faith-based organization in Jos (www.faithalivenigeria.org) that provides primary healthcare for about 10,000 patients a month and ongoing care for HIV/AIDS patients, as well as care for emergencies, opportunistic infections such as TB and Malaria.

SAMPLING METHOD

Consenting HIV-infected adults will be stratified by sex and age interval of 5yrs on a proportionally representative basis from a sampling frame obtained from the register of patients attending HIV clinics at JUTH and FAF who satisfy the inclusion criteria. Consenting HIV-infected adults randomly selected e.g. using computer- generated assigned numbers will be included in the study until the sample size is attained.

For the controls, eligible non HIV-negative individuals stratified by sex and age interval of 5yrs to mach for each case will be selected proportionally from a sampling frame of individuals obtained from the register of JUTH and FAF out-patient clinics. The recruitment of the controls will be done randomly e.g. using computer- generated assigned numbers.

Inclusion Criteria for subjects

  1. All ART-treated HIV-infected adults between 20 and 70 years (inclusive) enrolled at JUTH and FAF HIV clinic
  2. Patients who give an informed consent
  3. Non-diabetic- based on Medical records, Random Blood Glucose (RBG) < 11.1mmol/L and/or Fasting Blood Glucose < 7.0 mmol/L.
  4. Non-hypertensive -  Systolic Blood Pressure (SBP) < 140mmHg and Diastolic Blood Pressure (DBP) < 90 mmHg.
  5. Viral load undetectable (plasma HIV-1 RNA < 20 copies per milliliter) at last testing (within 1 yr of the study).

Exclusion Criteria for subject

  1. Patient who did not give consent
  2. HIV-naïve patients
  3. Diabetic-  based on Medical records, RBG ≥ 11.1mmol/L and/or FBG  ≥ 7.0 mmol/L
  4. Hypertensive-  SBP ≥ 140mmHg and/or DBP ≥ 90 mmHg
  5. Patients with confirmed CVD (stroke, myocardial infarction, and/or peripheral vascular disease), malignancy and active infection (as per the attending physicians and medical records), receiving glucocorticoids, growth hormone or other anabolic agents within the past 6 months.
  6. Patient who are too sick to partake in the study
  7. Pregnancy
  8. Patients on current ART regimen for less than 6 months 

Inclusion Criteria for controls

  1. Non HIV-infected (based on negative HIV screening) adults between 20 and 70 years (inclusive)  
  2. Non-diabetic-  based on Medical records, RBG < 11.1mmol/L and/or FBG  < 7.0 mmol/L
  3. Non-hypertensive-  SBP < 140mmHg and DBP < 90 mmHg
  4. No previous history of CVD

Exclusion Criteria for controls

  1. Unable to provide consent
  2. Diabetic-  based on Medical records, RBG ≥ 11.1mmol/L and/or FBG  ≥ 7.0 mmol/L
  3. Hypertensive-  SBP ≥ 140mmHg and/or DBP ≥ 90 mmHg
  4. Confirmed CVD (stroke, myocardial infarction, and/or peripheral vascular disease), malignancy, active infection (as per the attending physicians and medical records), receiving glucocorticoids, growth hormone or other anabolic agents within the past 6 months.
  5. Too ill to partake in the study
  6. Pregnancy

STUDY PROTOCOL

All consecutive patients who satisfy the inclusion criteria and give consent will be recruited into the study and those not willing to participate in the study will be excluded. All eligible participants will be advised on the participation dates and time (Between 8:00am to 9:30am) at their clinic and will be advised to provide a fasting blood sample. Participants who could not come on the scheduled date will be rescheduled if they give prior notice to be excused or replaced if no notice was given.

Relevant clinical data will be obtained from each participant with the aid of a standardised questionnaire. The questionnaire was filled by the researcher or his trained assistant. The questionnaire will address the following areas; socio-demographic data, cardiovascular risks factors, previous diseases and co-medications. Information regarding HIV related factors shall be obtained from patients records: known duration of HIV infection, WHO stage, start date of ART, current ART regimen, and previous changes in regimen. Hepatitis B or C co-infection. The latest CD4 cell count and HIV viral load will be recorded if done within the last 12 months taking into account the routinely follow-up duration of 12 months for viral load testing for stable patients in the treatment programme for HIV/AIDS.

Also relevant history of CVD risk factors will be sought for, including: lifestyle characteristics (exercise, diet, history of smoking and alcohol use), family history of CVD (hypertension, stroke, myocardial infarction and sudden death) as well as any concurrent medication that might affect CVD risk (anti-hypertensive drugs, non-steroidal anti-inflammatory drugs (NSAIDs), and lipid lowering drugs).

Biophysical examination will include measures such as Height, weight, waist circumference, and blood pressure will be measured according to standard procedures. Body mass index (BMI) was calculated. Obesity and overweight were defined as a BMI ≥30 and ≥25 kg/m2, respectively. Hypertension was defined as systolic blood pressure ≥140 mm Hg and/or diastolic blood pressure ≥ 90 mm Hg and/or the use of antihypertensive medication. Diabetes mellitus (DM) will be determined by medical history of confirmed DM (from patients’ records), in the absence of which FBG ≥ 7.0mmol/L and/or RBG ≥ 11.1 mmol/L will suffice. Metabolic syndrome (MetS) will be defined according to the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATPIII) guidelines.9

Blood samples will be collected in the morning after a 10-12 hr overnight fast. Four mls of blood will be drawn into a plain vacutainer for lipid profile; 3mls into a fluoride oxalate vacutainer for glucose assay. The specimens will be centrifuged at 4000rpm for 10minutes and the supernatant, plasma or serum separated out. Plasma glucose will be analysed daily while aliquots for lipid profile and assays will be stored at -70°C in a well-monitored freezer for one month until the analyses are performed. Heavily haemolysed, icteric or lipaemic samples were excluded.

Biochemical analysis

Fasting plasma glucose concentration will be measured using Glucose oxidase method, Total cholesterol (TC), Triglyceride (TG) and High Density Lipoprotein-Cholesterol (HDL-C) will be analyzed with standard enzymatic methods, while Low Density Lipoprotein-Cholesterol (LDL-C) will be determined by a direct, homogenous assay. All assays will be ran on a Roche Cobas C111 analyzer (Roche diagnostics, Germany). The LDL-C method will be employed to avoid the limitation of the routinely used Friedewald equation,32 which cannot be applied when TG > 400mg/dl as a very likely scenario in HIV patients on ARTs.

CIMT Measurement

This will be done (Within one week of the collection of blood samples) by a certified and experienced radiologist using high resolution real time ultrasound scanner GE Logic 5 color Doppler scanner (2007) with 7.5MHz linear probe. The right and left carotid arteries will be studied with the subject in spine position, head in the midline position and hyperextended. The common carotid artery (CCA) will be located, its origin traced as proximally as possible and the probe traced along the artery to the carotid bifurcation. Multiple transverse views (to obtain the near and far walls) and longitudinal views (to obtain the maximal luminal diameter) of the artery will be undertaken. The IMT will be taken in the longitudinal plane at the point of maximal thickness on the far wall of the CCA, at a point 1cm proximal to the bifurcation. The machine will be frozen and using its caliper markers, the IMT will be measured as the distance between the inner echogenic line representing the intima-blood interface and the outer echogenic line representing the media-adventitia junction. Magnification of the image will be used to improve accuracy of the caliper placement. The average value of three different measurements will be recorded for both left and right common carotid arteries respectively. Permission will be obtained from one in every 10 subjects, for a rescan for quality control purposes.

Subclinical atherosclerosis will be defined using a cut-off value of CIMT ≥ 0.78 mm, based on the previous study which showed that on average, a healthy adult reaches a CIMT of 0.78 mm at the age of 76 years.33

Cardiovascular risk prediction Models

The cardiovascular risk prediction models and there required variables are summarised in table 1 below:

 

10-year Framingham CVD risk score (FRS10).34,35

5-year Data Collection on Adverse Effects on Anti-HIV Drugs Cohort;(DAD ) risk score.36

Prospective Cardiovascular Munster Study (PROCAM) 10-year CVD risk.37

Systematic Coronary Risk Evaluation (SCORE)

10-year CVD.38

 

 

 

 

 

 

Age

Age

Age

Age

 

Gender

Gender

Gender

Gender

 

TC

TC

TG

TC

 

HDL-C

HDL-C

HDL-C

HDL-C

 

LDL-C

 

 

SBP

SBP

SBP

SBP

 

Smoking Status

Smoking Status (past)

 

Smoking Status (current )

smoking status

smoking status

 

 

Current treatment of High blood pressure

 

 

diabetes mellitus

diabetes mellitus

 

 

 

family history of CVD

family history of coronary heart disease

 

 

 

current use of abacavir, indinavir, or lopinavir

 

 

 

 

Duration on PI (indinavir and lopinavir )

 

 

 

 

 

 

 

Other Requirements/

considerations

≥ 20 years, No

no diabetes and no history of CVD,

≥2 risk factors

CD4 Count

Duration on NRTI

 

 

 

 

 

 

 

Risk classifications

Low= <10%

Moderate= 10–20%

High= >20 %

Low (<1 %), Moderate (1–5 %),

 High (5–10 %),

Very high (>10 %)

Low= <10%

Medium= 10–20%

High= >20 %

Risk chart for High-risk countries will be used

 

To simplify comparison, High- and very high-risk 5-year DAD risk score will be subsequently reclassified into a single high-risk category (≥ 5%).

 

The DAD risk score will be calculated using web based risk calculator (http://www.cpHIV.dk/ TOOLS/tabid/437/Default.aspx).The PROspectiveCArdiovascularMünster study (PROCAM) wil be calculated using web based risk calculator http://www.thecalculator.co/health/PROCAM-Score-For-Cardiovascular-Risk-Calculator-985.html. The SCORE will be computed via an application available at: http://www.heartscore.org/Pages/download.aspx

DATA PROCESSING AND STATISTICAL ANALYSIS

Data will be entered in Microscoft Excel® version 2.0 and exported to Statistical Package for Social Sciences (SPSS® Incorporated Chicago Version 18.0) software for analysis. Descriptive statistics will be presented as mean values + standard deviation (SD) or medians with interquartile ranges (IQRs) for none normal continuous variables, and proportions (as percentages) for categorical variables. Kolmogorov-Smirnov test will be used to test for normality of continuous variables. unpaired students t-test or Mann-whitney U test will be used to test the difference in means or medians of continuous variables between groups. Subclinical atherosclerosis, defined as CIMT ≥0.78 mm, will be the primary outcome variable. Other outcomes variables will include risk classification of the various cardiovascular risk assessment scoring systems (low, moderate or high risk). Chi square test will be used to compare the proportions of subclinical atherosclerosis in cases and control groups. Bivariate analysis (chi square) and multivariate logistic regression will be used to examine the relationship between risk factors and CVD risk prediction models with subclinical atherosclerosis. The agreement between different CVD risk assessment algorithms will be assessed using the kappa coefficient. The significance level was set at p≤ 0.05.

ETHICAL CONSIDERATION

 This study will be carried out after due approval from the Ethical Committee of the Jos University Teaching Hospital (JUTH) and FAF Jos. Informed consent will obtained from all participants after due explanation of the research work and procedure.. Anonymity and confidentiality of the information obtained from the participants in this study will be assured and maintained.

REFERENCES

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