|Year : 2019 | Volume
| Issue : 2 | Page : 93-97
Lipid and apoprotein markers and carotid intima-media thickness among hypertensive Nigerians
Modupe Akinrele Kuti1, Abiodun Moshood Adeoye2, Samuel Ayodeji Agboola1, Tolulope Olutosin Omilakin3
1 Department of Chemical Pathology, College of Medicine, University of Ibadan, Ibadan, Nigeria
2 Department of Medicine, College of Medicine, University of Ibadan, Ibadan, Nigeria
3 Department of Ophthalmology, Eleta Eye Institute, Ibadan, Nigeria
|Date of Submission||20-Oct-2018|
|Date of Decision||08-Feb-2019|
|Date of Acceptance||12-Apr-2019|
|Date of Web Publication||11-Nov-2019|
Dr. Modupe Akinrele Kuti
Department of Chemical Pathology, College of Medicine, University of Ibadan, Ibadan
Source of Support: None, Conflict of Interest: None
Context: Measurement of lipids and apoproteins are essential components aimed at reducing the global burden of atherosclerotic cardiovascular disease. Carotid intima-media thickness (CIMT) has been widely accepted as an index of subclinical atherosclerosis. A relationship between CIMT and the parameters of the traditional lipid profile has been described.
Aim: Evaluation of the diagnostic character of lipid and apoprotein markers, which are cheap and easy to perform, in detecting a significant thickening of the carotid intima media in hypertensive persons.
Subjects and Methods: Cross-sectional study of adult male hypertensive persons with fasting measurement of the traditional lipid profile and apoprotein B. CIMT of the common carotid artery was determined by ultrasound in all participants.
Results: The mean CIMT was significantly higher among the hypertensive participants than normotensive controls. Age, systolic blood pressure, triglycerides, low-density lipoprotein-cholesterol (LDL-C), and Apo B were all significantly associated with CIMT. Hypertensive persons with CIMT ≥1.00 mm had significantly higher serum concentrations of total cholesterol (TC), LDL-C, and Apo B. The positive predictive value of a result (TC >200 mg/dL, LDL-C >130 mg/dL, and Apo B >100 mg/dL) was <50%, while that for a negative result (TC <200 mg/dL, LDL-C <130 mg/dL, and Apo B <100 mg/dL) approached or was equal to 100%.
Conclusions: There is some relationship between dyslipidemia and significant thickness of the carotid intima media. The levels of TC, LDL-C, and Apo B in plasma, which are cheaper and easier to determine, may help in the selection of hypertensive persons to be offered CIMT assessment.
Keywords: Apoprotein B, carotid intima-media thickness, cholesterol
|How to cite this article:|
Kuti MA, Adeoye AM, Agboola SA, Omilakin TO. Lipid and apoprotein markers and carotid intima-media thickness among hypertensive Nigerians. Nig J Cardiol 2019;16:93-7
|How to cite this URL:|
Kuti MA, Adeoye AM, Agboola SA, Omilakin TO. Lipid and apoprotein markers and carotid intima-media thickness among hypertensive Nigerians. Nig J Cardiol [serial online] 2019 [cited 2020 Jan 29];16:93-7. Available from: http://www.nigjcardiol.org/text.asp?2019/16/2/93/270687
| Introduction|| |
Primary and secondary preventive measures aimed at reducing the increasing global burden of atherosclerotic cardiovascular diseases (ASCVDs) require the measurement of lipids, and more recently apoprotein markers in blood as a part of risk assessment and cholesterol-lowering therapy. This is based on several lines of evidence. Several landmark epidemiological studies, including the Framingham Heart Study and the Seven Countries Study established a link between levels of total cholesterol (TC) and risk of coronary heart disease.,, In addition, the observation that genetic defects in receptor-mediated pathways for cholesterol homeostasis, which result in very high cholesterol levels, are associated with myocardial infarction, especially at a younger age. Finally, the fatty streak, the initial lesions in atherosclerosis, and the evolution of the same into an atheroma reflect the accumulation of lipids and lipoproteins in the intima of the affected arterial wall. Although these lesions may occur in any part of the vasculature, they have a predilection for certain portions of the coronary circulation, the renal arteries and the extracranial carotid artery. The progression of these lesions is usually a slow process that remains subclinical for a long time.
The thickness of the intima media of the carotid artery reflects the subclinical atherosclerosis burden present in vivo, and it has been demonstrated to have a strong relationship with cardiovascular disease., The measurement of the combined thickness of the intimal and medial layers of the carotid artery by B-mode ultrasound is what constitutes carotid intima-media thickness (CIMT). CIMT has gained prominence as a noninvasive tool that can be measured reproducibly and predicts stroke and myocardial infarction. Furthermore, it has been shown that treatment for dyslipidemia may result in a regression in CIMT measurements. This forms the basis for its widespread use in clinical, epidemiological studies where, by serving as a primary outcome in the place of the myocardial infarction and stroke, it reduces the cost of studies and duration of follow-up.
There are traditional laboratory measures of lipid and lipoprotein metabolism that are used in the assessment of ASCVD risk. The advantage of these markers is they are typically cheaper, easier to perform, and more amenable to large population screening than CIMT in most environments. Given the advantage however of CIMT as a more direct measure, the intention of the current study is to assess its relationship with the traditional lipid markers and apoprotein B. This was done among persons with hypertension. Hypertension, as well as age, may induce some thickening of the arterial walls. The diagnostic characteristics of these lipid markers in identifying hypertensive individuals with significant CIMT were determined.
| Subjects and Methods|| |
This was a cross-sectional study with recruitment from among the hypertensive persons attending the adult cardiology clinic of the University College Hospital, Ibadan, Nigeria. Consecutively, consenting persons were recruited if they were not diabetic, on hypolipidemic therapy, or smokers. A structured questionnaire was used to collect demographic and clinical information. Weight and height were measured, and the body mass index was calculated. Age-matched controls were recruited from normotensive persons attending other medical clinics of the University College Hospital, Ibadan, Nigeria.
Fasting venous blood was obtained into serum separator vacutainer bottles for fasting TC, triglycerides (TG), high-density lipoprotein-cholesterol (HDL-C), Apoprotein B, and Apoprotein A1 measurements. Low-density lipoprotein-cholesterol (LDL-C) was calculated using the Friedewald formula (LDL-C = TC minus [HDL-C plus TG/2.22]). Fluoride oxalate specimens were also collected for fasting glucose studies. All analyses were carried out on the Landwind C100 plus (Landwind Medicals, Schenzen, China). TC, LDL-C, HDL-C, and TG were measured by enzymatic methods, while apoprotein B and A1 were measured by immunoturbidimetry.
Carotid intima-media thickness measurements
Carotid ultrasonic examination was performed with a 7.5-MHz linear-array transducer (Toshiba, Nemio ultrasonic machine). The participants were placed in the supine position with the neck slightly extended and head turned away from the side of examination. CIMT was defined as the distance from the lumen-intima interface to the media-adventitia interface of the common carotid arteries. We measured the CIMT in the left and right common carotid arteries at the near and far walls in every participant. Using the technique of “multiple carotid sites measurement,” and an average of least three measurements taken at 1–1.5 cm away from the carotid bulb was recorded. We first calculated the average CIMT of the near and far walls of the left and right common carotid arteries and then calculated the average of the bilateral carotid arteries.
Statistical analyses were performed using Statistical Package for Social Sciences (SPSS) version 21 (SPSS, Chicago, Illinois, USA). Statistical significance was set at P < 0.05.
Ethical approval was obtained from the University of Ibadan/University College Hospital Ethics Committee.
| Results|| |
Fifty-two hypertensive adults, comprising 21 males and 30 females, aged between 18 and 73 years were recruited for the study. Twenty-five normotensive apparently healthy and age-matched persons were recruited as controls. [Table 1] shows the demographic, clinical, and laboratory profile of the groups of participants. The mean age of all the hypertensive participants was 46.5 ± 9.8 years, and for the normotensive participants, 45.4 ± 13.5 years. The difference was not statistically significant at P = 0.684. The mean CIMT was significantly higher among the hypertensive participants than the normotensive controls (0.77 ± 0.21 mm versus 0.66 ± 0.14 mm, P = 0.027). [Table 2] shows the relationship between clinical and laboratory parameters with CIMT measurements among the hypertensives. Age, systolic blood pressure, waist–hip ratio, TG, LDL-C, and Apo B were all significantly associated with CIMT with P ≤ 0.001, 0.045, 0.007, 0.019, 0.012, and 0.030, respectively.
|Table 2: Association of carotid intima-media thickness with clinical and laboratory parameters among hypertensive participants|
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Hypertensive persons with CIMT ≥1.00 mm had significantly higher serum concentrations of TC (227.1 ± 18.1 vs. 182.3 ± 33.9 mg/dL; P < 0.001), TG (120.9 ± 45.3 vs. 79.0 ± 37.2 mg/dL; P < 0.001), LDL-C (151.8 ± 32.3 vs. 106.0 + 28.8 mg/dL; P < 0.001), Apo B (1.5 ± 0.19 vs. 1.1 ± 0.24 g/dL; P < 0.001) as well as higher Apo B/Apo A1 ratios (0.76 ± 0.08 vs. 0.67 ± 0.06; P = 0.03). TC >200 mg/dL, LDL-C >130 mg/dL, and Apo B values >100 mg/dL were all significantly associated with CIMT >1.00 mm; χ2 = 15.92, P < 0.001, χ2 = 14.00, P < 0.001, χ2 = 5.04, P = 0.025, all respectively.
[Table 3] shows the diagnostic characteristics of the lipid and apoprotein metrics in identifying those hypertensive participants with CIMT >1.00 mm. The parameters with the highest sensitivity were TC >200 mg/dL and Apo B >100 mg/dL. The positive likelihood ratios for the TC >200 mg/dL, LDL-C >130 mg/dL, and Apo B >100 mg/dL values were 1.43, 1.66, and 1.31, respectively, while the negative likelihood ratios were 0, 0.12, and 0 also, respectively. The predictive value of a positive result (TC >200 mg/dL, LDL-C >130 mg/dL, and Apo B >100 mg/dL) was < 50% for all the parameters, while that for a negative result approached or was equal to 100% for LDL-C <130 mg/dL, TC <200 mg/dL, and Apo B <100 mg/dL. The likelihood ratio of a positive result was <10 for all the parameters, while that of a negative result approached 0 for TC >200 mg/dL and Apo B >100 mg/dL.
|Table 3: Diagnostic characteristics of lipid and apoprotein metrics for carotid intima-media thickness >1.0 mm|
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| Discussion|| |
It is interesting and significant that in the environment of increased blood pressure and its attendant effects on the endothelial cell wall that this study showed that certain lipid metrics retain significant associations with the thickness of the carotid intima media. The higher the levels of the surrogate measures of the proatherogenic LDL, namely, LDL-C and Apoprotein B, the significantly higher the CIMT among our hypertensives. These findings agree with those of Zhao et al. in their study of Chinese hypertensives. They reported that LDL-C was significantly greater in hypertensives with carotid plaques than those without. They, however, did not measure Apo B. Our study provides further evidence that dyslipidemia confers significant additional cardiovascular risk in the hypertensives. This is probably due to the consequent pathology of both disorders, dyslipidemia and hypertension, terminating in thickening of the arterial wall, although through different mechanisms. Dyslipidemia induces arterial wall thickening through the process of atherosclerosis with oxidatively modified lipoproteins taken up by macrophages resulting in the production of cytokines and growth factors that induce the proliferation of smooth muscle cells, and which secrete extracellular matrix of the characteristic fibrous tissue of the fibrofatty atheroma. Hypertension, in addition to inducing atherosclerosis through oxidative stress and endothelial dysfunction, also induces arterial thickening through the process of arteriolosclerosis. This is characterized by the accumulation of various serum proteins in the subendothelial space as a result of the altered shear stress induced by hypertension. The injury to the endothelial wall as well as vascular cell proliferation, due to hypertension, can amplify the atherosclerotic process. This suggests that the increased CIMT in the hypertensive with dyslipidemia is the product of a pathologic synergy.
In light of the above, we examined for the clinical utility of traditional lipid indices and apoprotein B in identifying hypertensive individuals with CIMT >1.00 mm. We found markedly varying utility of the various lipid and apoprotein markers in identifying these individuals. Our results show that the potential benefit of currently used cutoff concentrations of these markers might lie in their ability to identify those in whom a CIMT assessment may not return a clinically significant value and may therefore not be indicated. This is based on the very low value of the likelihood ratio of a negative result for TC <200 mg/dL and Apo B <100 mg/dL. The results indicate that an individual who has values below these set points is unlikely to have a CIMT >1.00 mm. The daily practical application of this low likelihood ratio negative can be estimated to mean that for any pretest probability that may exist for requesting CIMT, TC <200 mg/dL or Apo B <100 mg/dL decreases the likelihood of a CIMT >1.00 mm by about 50%. This information may then be used to guide the need to order the test, subject to other clinical considerations (pretest probabilities).
| Conclusions|| |
We have demonstrated the synergy that exists between hypertension and dyslipidemia with regards to thickening of the endothelial wall of the carotid artery. We have also suggested a potential utility of this knowledge to optimize the request for CIMT in the hypertensive.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3]