EURO PEAN SO CIETY O F CARDIOLOGY ®
Original scientific paper
Can common carotid intima media thickness serve as an indicator of both cardiovascular phenotype and risk among black Africans?
European Journal of Preventive Cardiology 2015, Vol. 22(11) 1442–1451 ! The European Society of Cardiology 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/2047487314547656 ejpc.sagepub.com
MO Owolabi1,2, AM Agunloye2,3, EO Umeh3 and OM Akpa2,4
Abstract Background: It is not known whether common carotid intima media thickness (CIMT) can serve as a surrogate marker of cardiovascular risk among black Africans. Therefore, we examined whether CIMT differed significantly among individuals with distinct cardiovascular phenotype and correlated significantly with traditional cardiovascular risk factors in a black African population. Methods: CIMTwas measured in 456 subjects with three distinct cardiovascular phenotypes – 175 consecutive Nigerian African stroke patients, 161 hypertensive patients without stroke and 120 normotensive non-smoking adults. For each pair of cardiovascular phenotypes, c-statistics were obtained for CIMT and traditional vascular risk factors (including age, gender, weight, waist circumference, smoking, alcohol, systolic and diastolic blood pressures, fasting plasma glucose, fasting total cholesterol). Pearson’s correlation coefficients were calculated to quantify bivariate relationships. Findings: Bilaterally, CIMT was significantly different among the three cardiovascular phenotypes (right: p < 0.001, F ¼ 33.8; left: p < 0.001, F ¼ 48.6). CIMT had a higher c-statistic for differentiating stroke versus normotension (c ¼ 0.78 right; 0.82 left, p < 0.001) and hypertension versus normotension (c ¼ 0.65 right; 0.71 left, p < 0.001) than several traditional vascular risk factors. Bilaterally, combining all subjects, CIMT was the only factor that correlated significantly (right: 0.12 r 0.41, 0.018 p < 0.0001; left: 0.18 r 0.41, 0.005 p < 0.0001) to all the traditional cardiovascular risk factors assessed. Conclusion: Our findings support CIMT as a significant indicator of both cardiovascular risk and phenotype among adult black Africans. However, specific thresholds need to be defined based on prospective studies.
Keywords Carotid intima media thickness, hypertension, stroke, cardiovascular risk marker, surrogate marker Received 28 April 2014; accepted 27 July 2014
Introduction Cardiovascular disease is the leading cause of death globally with a disproportionately heavier load among low and middle income countries (LMICs).1–3 Suitable biomarkers for estimating total cardiovascular risk load are needed to facilitate the assessment of impact of interventions aimed at reducing this burden in individuals. Such a biomarker, ideally utilizing a single parameter, would be especially beneficial for monitoring the effect of preventive strategies,4 which remain the most cost-effective means of combating the escalating cardiovascular burden in LMICs.
Complex risk calculators such as the Framingham risk score and United Kingdom Prospective Diabetes Study (UKPDS) risk engine utilizing multiple 1
Department of Medicine, University College Hospital, Ibadan, Nigeria College of Medicine, University of Ibadan, Nigeria 3 Department of Radiology, University College Hospital, Ibadan, Nigeria 4 Department of Epidemiology and Medical Statistics, College of Medicine, University of Ibadan, Nigeria 2
Corresponding author: Mayowa O Owolabi, Department of Medicine, University College Hospital, Ibadan, 200001 Oyo State, Nigeria. Email: [email protected]
Downloaded from cpr.sagepub.com at Duke University Libraries on November 14, 2015
Owolabi et al.
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parameters have been explored among various populations (predominantly whites in high income countries – HICs).2,5 However, it is doubtful if their risk prediction equations based on data from those populations can be suitably extrapolated to other populations (including LMICs). Ultrasound measurement of carotid intima media thickness (CIMT) is a potential cardiovascular risk biomarker utilizing a single parameter. It is a relatively low-cost, highly reproducible, rapidly measurable, non-invasive imaging technique ideal for resourcepoor settings such as LMICs.2,5–7 It is accurate for detecting and quantifying atherosclerosis, which is the underlying cause of the majority of clinical cardiovascular events in adults.2,5–7 Increased CIMT is one of the first detectable stages of atherosclerosis2,5 and it reflects the degree of atherosclerosis elsewhere in the arterial system thereby predicting cardiovascular risk.5 However, the exact risk of cardiovascular events associated with an increased CIMT is not known particularly among black Africans.2,5 Moreover, the value of CIMT measurement in comparison with traditional vascular risk factors is not entirely clear.2,8,9 While Peters (in systematic reviews) and Sibal reported considerable evidence for CIMT as a risk marker,4,8,10 van den Oord (in a meta-analysis) concluded that the addition of CIMT to traditional cardiovascular risk prediction models did not lead to a statistically significant increase in performance of those models.2 Similarly, Lorenz in a meta-analysis of individual participant data, submitted that there was no conclusive evidence for use of CIMT progression as a surrogate marker.11 These reviews and metaanalyses were, however, limited to publications emanating from Europe, USA and China with none from LMICs in Africa.2,4,8,11 Because of racial and geographical disparity in atherosclerosis,12 cardiovascular disease burden and trends,13–16 their observations may not apply to black Africans.2 The usefulness of CIMT as a surrogate marker of cardiovascular risk is unknown among black Africans. Therefore, in line with Prentice criteria,4 we examined if CIMT differed among individuals of distinct cardiovascular phenotype and correlated significantly with established (traditional) cardiovascular risk factors among black African stroke patients, hypertensive subjects and normotensive adults.
Methods Participants We recruited 175 consecutive adult (18 years) stroke patients17 of both sexes in the Medicine Department of the University College Hospital, Ibadan between 2008
and 2010. Eligible patients were evaluated within one week of admission. One hundred and sixty-one adult (18 years) volunteering hypertensive patients of both sexes without history of transient ischaemic attacks (TIA), stroke, coronary artery disease, heart failure or kidney disease were also consecutively enrolled from the Medical Outpatient Clinic during the study period. Additionally, we recruited 120 volunteering normotensive, non-smoking adults (18 years) of both sexes with no known history or symptoms of diabetes mellitus or symptoms suggestive of pathology of vascular origin.
Ethics statement Ethical approval was obtained from the ethical review committee of the University of Ibadan/University College Hospital, Ibadan. Written informed consent was obtained from all normotensive subjects and hypertensive patients while verbal informed consent was obtained from illiterate stroke patients (uneducated, unable to read or write) and stroke patients with arm paralysis (unable to write).
Clinical, laboratory and ultrasound evaluation Demographic and clinical data including age, sex, weight, height and waist circumference were collected from the patients using standard procedures.17 Brachial artery BP was obtained from all subjects at entry with a mercury sphygmomanometer (Accoson, England) using the standard method.17 Hypertension was defined as previous diagnosis of or ongoing treatment for hypertension or a record of sustained BP 140/ 90 mmHg on two or more occasions.18,19 History of cigarette smoking and alcohol consumption were obtained while fasting plasma glucose and fasting total cholesterol were measured in the subjects. Sonography of the extracranial carotid arteries was performed on every eligible patient within 1 week of recruitment into the study. Sonograms were acquired with a LOGIQ P5 ultrasound machine and a 5–8 MHz multifrequency linear transducer (GE Healthcare, Waukesha, WI). Using published guidelines,5,8 the common carotid arteries (CCA) on each side of the neck were examined with the patients in the conventional position (supine with the head turned away from the side to be examined) to adequately visualize the vessels. To obtain an optimal image, the sound waves were beamed perpendicularly to the arteries to show the two parallel echogenic lines that correspond to the lumen–intima and media– adventitia interfaces. For standardization, the IMT of the CCA was measured in the mid-portion of the vessel in an area devoid of plaques. The IMT is the
Downloaded from cpr.sagepub.com at Duke University Libraries on November 14, 2015
1444
European Journal of Preventive Cardiology 22(11)
distance between the leading edge of the first bright line on the far wall (lumen–intima interface) and the leading edge of the second bright line (media–adventitia interface). The images for the IMT measurement were manually magnified to minimize error in measurement and the IMT was measured, avoiding plaques, at its far wall. This technique was selected in preference to the ‘multiple carotid sites measurement’ because it is easier and quicker to assess thus enabling its widespread utility in everyday clinical and communitybased settings (sometimes with automation).5,8,20,21 Besides, common carotid CIMT is more reliable to measure than multiple site CIMT,22 and it is as good as multiple site CIMT in improving risk prediction.22
when the c-statistic is higher than 0.7 and strong when c exceeds 0.8.23 A value approaching 1.0, as sometimes reported in the literature,24–26 indicates an excellent model that can almost perfectly identify those within a group or otherwise. Bivariate relationship between CIMT and vascular risk factors were explored using Student’s t-test for between-group comparisons and Pearson’s product moment correlation for continuous variables. All analyses were performed with SPSS version 15 (SPSS Chicago Inc.) while p-value
Original scientific paper
Can common carotid intima media thickness serve as an indicator of both cardiovascular phenotype and risk among black Africans?
European Journal of Preventive Cardiology 2015, Vol. 22(11) 1442–1451 ! The European Society of Cardiology 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/2047487314547656 ejpc.sagepub.com
MO Owolabi1,2, AM Agunloye2,3, EO Umeh3 and OM Akpa2,4
Abstract Background: It is not known whether common carotid intima media thickness (CIMT) can serve as a surrogate marker of cardiovascular risk among black Africans. Therefore, we examined whether CIMT differed significantly among individuals with distinct cardiovascular phenotype and correlated significantly with traditional cardiovascular risk factors in a black African population. Methods: CIMTwas measured in 456 subjects with three distinct cardiovascular phenotypes – 175 consecutive Nigerian African stroke patients, 161 hypertensive patients without stroke and 120 normotensive non-smoking adults. For each pair of cardiovascular phenotypes, c-statistics were obtained for CIMT and traditional vascular risk factors (including age, gender, weight, waist circumference, smoking, alcohol, systolic and diastolic blood pressures, fasting plasma glucose, fasting total cholesterol). Pearson’s correlation coefficients were calculated to quantify bivariate relationships. Findings: Bilaterally, CIMT was significantly different among the three cardiovascular phenotypes (right: p < 0.001, F ¼ 33.8; left: p < 0.001, F ¼ 48.6). CIMT had a higher c-statistic for differentiating stroke versus normotension (c ¼ 0.78 right; 0.82 left, p < 0.001) and hypertension versus normotension (c ¼ 0.65 right; 0.71 left, p < 0.001) than several traditional vascular risk factors. Bilaterally, combining all subjects, CIMT was the only factor that correlated significantly (right: 0.12 r 0.41, 0.018 p < 0.0001; left: 0.18 r 0.41, 0.005 p < 0.0001) to all the traditional cardiovascular risk factors assessed. Conclusion: Our findings support CIMT as a significant indicator of both cardiovascular risk and phenotype among adult black Africans. However, specific thresholds need to be defined based on prospective studies.
Keywords Carotid intima media thickness, hypertension, stroke, cardiovascular risk marker, surrogate marker Received 28 April 2014; accepted 27 July 2014
Introduction Cardiovascular disease is the leading cause of death globally with a disproportionately heavier load among low and middle income countries (LMICs).1–3 Suitable biomarkers for estimating total cardiovascular risk load are needed to facilitate the assessment of impact of interventions aimed at reducing this burden in individuals. Such a biomarker, ideally utilizing a single parameter, would be especially beneficial for monitoring the effect of preventive strategies,4 which remain the most cost-effective means of combating the escalating cardiovascular burden in LMICs.
Complex risk calculators such as the Framingham risk score and United Kingdom Prospective Diabetes Study (UKPDS) risk engine utilizing multiple 1
Department of Medicine, University College Hospital, Ibadan, Nigeria College of Medicine, University of Ibadan, Nigeria 3 Department of Radiology, University College Hospital, Ibadan, Nigeria 4 Department of Epidemiology and Medical Statistics, College of Medicine, University of Ibadan, Nigeria 2
Corresponding author: Mayowa O Owolabi, Department of Medicine, University College Hospital, Ibadan, 200001 Oyo State, Nigeria. Email: [email protected]
Downloaded from cpr.sagepub.com at Duke University Libraries on November 14, 2015
Owolabi et al.
1443
parameters have been explored among various populations (predominantly whites in high income countries – HICs).2,5 However, it is doubtful if their risk prediction equations based on data from those populations can be suitably extrapolated to other populations (including LMICs). Ultrasound measurement of carotid intima media thickness (CIMT) is a potential cardiovascular risk biomarker utilizing a single parameter. It is a relatively low-cost, highly reproducible, rapidly measurable, non-invasive imaging technique ideal for resourcepoor settings such as LMICs.2,5–7 It is accurate for detecting and quantifying atherosclerosis, which is the underlying cause of the majority of clinical cardiovascular events in adults.2,5–7 Increased CIMT is one of the first detectable stages of atherosclerosis2,5 and it reflects the degree of atherosclerosis elsewhere in the arterial system thereby predicting cardiovascular risk.5 However, the exact risk of cardiovascular events associated with an increased CIMT is not known particularly among black Africans.2,5 Moreover, the value of CIMT measurement in comparison with traditional vascular risk factors is not entirely clear.2,8,9 While Peters (in systematic reviews) and Sibal reported considerable evidence for CIMT as a risk marker,4,8,10 van den Oord (in a meta-analysis) concluded that the addition of CIMT to traditional cardiovascular risk prediction models did not lead to a statistically significant increase in performance of those models.2 Similarly, Lorenz in a meta-analysis of individual participant data, submitted that there was no conclusive evidence for use of CIMT progression as a surrogate marker.11 These reviews and metaanalyses were, however, limited to publications emanating from Europe, USA and China with none from LMICs in Africa.2,4,8,11 Because of racial and geographical disparity in atherosclerosis,12 cardiovascular disease burden and trends,13–16 their observations may not apply to black Africans.2 The usefulness of CIMT as a surrogate marker of cardiovascular risk is unknown among black Africans. Therefore, in line with Prentice criteria,4 we examined if CIMT differed among individuals of distinct cardiovascular phenotype and correlated significantly with established (traditional) cardiovascular risk factors among black African stroke patients, hypertensive subjects and normotensive adults.
Methods Participants We recruited 175 consecutive adult (18 years) stroke patients17 of both sexes in the Medicine Department of the University College Hospital, Ibadan between 2008
and 2010. Eligible patients were evaluated within one week of admission. One hundred and sixty-one adult (18 years) volunteering hypertensive patients of both sexes without history of transient ischaemic attacks (TIA), stroke, coronary artery disease, heart failure or kidney disease were also consecutively enrolled from the Medical Outpatient Clinic during the study period. Additionally, we recruited 120 volunteering normotensive, non-smoking adults (18 years) of both sexes with no known history or symptoms of diabetes mellitus or symptoms suggestive of pathology of vascular origin.
Ethics statement Ethical approval was obtained from the ethical review committee of the University of Ibadan/University College Hospital, Ibadan. Written informed consent was obtained from all normotensive subjects and hypertensive patients while verbal informed consent was obtained from illiterate stroke patients (uneducated, unable to read or write) and stroke patients with arm paralysis (unable to write).
Clinical, laboratory and ultrasound evaluation Demographic and clinical data including age, sex, weight, height and waist circumference were collected from the patients using standard procedures.17 Brachial artery BP was obtained from all subjects at entry with a mercury sphygmomanometer (Accoson, England) using the standard method.17 Hypertension was defined as previous diagnosis of or ongoing treatment for hypertension or a record of sustained BP 140/ 90 mmHg on two or more occasions.18,19 History of cigarette smoking and alcohol consumption were obtained while fasting plasma glucose and fasting total cholesterol were measured in the subjects. Sonography of the extracranial carotid arteries was performed on every eligible patient within 1 week of recruitment into the study. Sonograms were acquired with a LOGIQ P5 ultrasound machine and a 5–8 MHz multifrequency linear transducer (GE Healthcare, Waukesha, WI). Using published guidelines,5,8 the common carotid arteries (CCA) on each side of the neck were examined with the patients in the conventional position (supine with the head turned away from the side to be examined) to adequately visualize the vessels. To obtain an optimal image, the sound waves were beamed perpendicularly to the arteries to show the two parallel echogenic lines that correspond to the lumen–intima and media– adventitia interfaces. For standardization, the IMT of the CCA was measured in the mid-portion of the vessel in an area devoid of plaques. The IMT is the
Downloaded from cpr.sagepub.com at Duke University Libraries on November 14, 2015
1444
European Journal of Preventive Cardiology 22(11)
distance between the leading edge of the first bright line on the far wall (lumen–intima interface) and the leading edge of the second bright line (media–adventitia interface). The images for the IMT measurement were manually magnified to minimize error in measurement and the IMT was measured, avoiding plaques, at its far wall. This technique was selected in preference to the ‘multiple carotid sites measurement’ because it is easier and quicker to assess thus enabling its widespread utility in everyday clinical and communitybased settings (sometimes with automation).5,8,20,21 Besides, common carotid CIMT is more reliable to measure than multiple site CIMT,22 and it is as good as multiple site CIMT in improving risk prediction.22
when the c-statistic is higher than 0.7 and strong when c exceeds 0.8.23 A value approaching 1.0, as sometimes reported in the literature,24–26 indicates an excellent model that can almost perfectly identify those within a group or otherwise. Bivariate relationship between CIMT and vascular risk factors were explored using Student’s t-test for between-group comparisons and Pearson’s product moment correlation for continuous variables. All analyses were performed with SPSS version 15 (SPSS Chicago Inc.) while p-value
