• Users Online: 310
  • Home
  • Print this page
  • Email this page
Home About us Editorial board Search Ahead of print Current issue Archives Submit article Instructions Subscribe Contacts Login 


 
 Table of Contents  
ORIGINAL ARTICLE
Year : 2019  |  Volume : 16  |  Issue : 2  |  Page : 93-97

Lipid and apoprotein markers and carotid intima-media thickness among hypertensive Nigerians


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 Submission20-Oct-2018
Date of Decision08-Feb-2019
Date of Acceptance12-Apr-2019
Date of Web Publication11-Nov-2019

Correspondence Address:
Dr. Modupe Akinrele Kuti
Department of Chemical Pathology, College of Medicine, University of Ibadan, Ibadan
Nigeria
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/njc.njc_29_18

Rights and Permissions
  Abstract 


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 2019 Dec 11];16:93-7. Available from: http://www.nigjcardiol.org/text.asp?2019/16/2/93/270687




  Introduction Top


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.[1] 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.[2],[3],[4] 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.[5] 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.[6] 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.[7]

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.[8],[9] 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.[10] Furthermore, it has been shown that treatment for dyslipidemia may result in a regression in CIMT measurements.[11] 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.[12] 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.[10] The diagnostic characteristics of these lipid markers in identifying hypertensive individuals with significant CIMT were determined.


  Subjects and Methods Top


Study population

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.

Laboratory measurements

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.[13] 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 analysis

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 Top


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 1: Characteristics of study participants

Click here to view
Table 2: Association of carotid intima-media thickness with clinical and laboratory parameters among hypertensive participants

Click here to view


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

Click here to view



  Discussion Top


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.[14] 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.[15] Hypertension, in addition to inducing atherosclerosis through oxidative stress and endothelial dysfunction, also induces arterial thickening through the process of arteriolosclerosis.[16] 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.[17] The injury to the endothelial wall as well as vascular cell proliferation, due to hypertension, can amplify the atherosclerotic process.[18] 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%.[19] This information may then be used to guide the need to order the test, subject to other clinical considerations (pretest probabilities).


  Conclusions Top


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

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Leong DP, Joseph PG, McKee M, Anand SS, Teo KK, Schwalm JD, et al. Reducing the global burden of cardiovascular disease, part 2: Prevention and treatment of cardiovascular disease. Circ Res 2017;121:695-710.  Back to cited text no. 1
    
2.
Keil U. Coronary artery disease: The role of lipids, hypertension and smoking. Basic Res Cardiol 2000;95 Suppl 1:I52-8.  Back to cited text no. 2
    
3.
Castelli WP, Anderson K, Wilson PW, Levy D. Lipids and risk of coronary heart disease. The Framingham study. Ann Epidemiol 1992;2:23-8.  Back to cited text no. 3
    
4.
Verschuren WM, Jacobs DR, Bloemberg BP, Kromhout D, Menotti A, Aravanis C, et al. Serum total cholesterol and long-term coronary heart disease mortality in different cultures. Twenty-five-year follow-up of the seven countries study. JAMA 1995;274:131-6.  Back to cited text no. 4
    
5.
Brown MS, Goldstein JL. A receptor-mediated pathway for cholesterol homeostasis. Science 1986;232:34-47.  Back to cited text no. 5
    
6.
Kasper DL, editor. Harrison's Principles of Internal Medicine. 19th ed. New York: McGraw Hill Education; 2015.  Back to cited text no. 6
    
7.
Ross R. Atherosclerosis – An inflammatory disease. N Engl J Med 1999;340:115-26.  Back to cited text no. 7
    
8.
Chambless LE, Heiss G, Folsom AR, Rosamond W, Szklo M, Sharrett AR, et al. Association of coronary heart disease incidence with carotid arterial wall thickness and major risk factors: The atherosclerosis risk in communities (ARIC) study, 1987-1993. Am J Epidemiol 1997;146:483-94.  Back to cited text no. 8
    
9.
Li C, Engström G, Berglund G, Janzon L, Hedblad B. Incidence of ischemic stroke in relation to asymptomatic carotid artery atherosclerosis in subjects with normal blood pressure. A prospective cohort study. Cerebrovasc Dis 2008;26:297-303.  Back to cited text no. 9
    
10.
Cobble M, Bale B. Carotid intima-media thickness: Knowledge and application to everyday practice. Postgrad Med 2010;122:10-8.  Back to cited text no. 10
    
11.
Crouse JR 3rd, Raichlen JS, Riley WA, Evans GW, Palmer MK, O'Leary DH, et al. Effect of rosuvastatin on progression of carotid intima-media thickness in low-risk individuals with subclinical atherosclerosis: The METEOR trial. JAMA 2007;297:1344-53.  Back to cited text no. 11
    
12.
Ramasamy I. Update on the laboratory investigation of dyslipidemias. Clin Chim Acta 2018;479:103-25.  Back to cited text no. 12
    
13.
Simon A, Gariepy J, Chironi G, Megnien JL, Levenson J. Intima-media thickness: A new tool for diagnosis and treatment of cardiovascular risk. J Hypertens 2002;20:159-69.  Back to cited text no. 13
    
14.
Zhao X, Bo L, Zhao H, Li L, Zhou Y, Wang H, et al. Descriptive study of the relationship between the subclinical carotid disease and biomarkers, carotid femoral pulse wave velocity in patients with hypertension. Clin Exp Hypertens 2018;40:274-80.  Back to cited text no. 14
    
15.
Linton MF, Yancey PG, Davies SS, Jerome WG, Linton EF, Vickers KC. The role of lipids and lipoproteins in atherosclerosis. In: Feingold KR, Anawalt B, Boyce A, Chrousos G, Dungan K, Grossman A, et al, editors. Endotext. South Dartmouth (MA): MDText.com, Inc.; 2000.  Back to cited text no. 15
    
16.
Alexander RW. Theodore cooper memorial lecture. Hypertension and the pathogenesis of atherosclerosis. Oxidative stress and the mediation of arterial inflammatory response: A new perspective. Hypertension 1995;25:155-61.  Back to cited text no. 16
    
17.
Olson JL. Hyaline arteriolosclerosis: New meaning for an old lesion. Kidney Int 2003;63:1162-3.  Back to cited text no. 17
    
18.
Yang JW, Cho KI, Kim JH, Kim SY, Kim CS, You GI, et al. Wall shear stress in hypertensive patients is associated with carotid vascular deformation assessed by speckle tracking strain imaging. Clin Hypertens 2014;20:10.  Back to cited text no. 18
    
19.
McGee S. Simplifying likelihood ratios. J Gen Intern Med 2002;17:646-9.  Back to cited text no. 19
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

Top
 
 
  Search
 
Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

 
  In this article
Abstract
Introduction
Subjects and Methods
Results
Discussion
Conclusions
References
Article Tables

 Article Access Statistics
    Viewed450    
    Printed24    
    Emailed0    
    PDF Downloaded63    
    Comments [Add]    

Recommend this journal


[TAG2]
[TAG3]
[TAG4]