|Year : 2019 | Volume
| Issue : 2 | Page : 63-67
Coronary risk prediction by the correlation of total cholesterol/high-density lipoprotein, triglyceride/high-density lipoprotein, low-density lipoprotein/high-density lipoprotein ratios, non-high-density lipoprotein, apolipoprotein-B, and high-sensitivity C-reactive protein with low-density lipoprotein in Indian patients under statin therapy
AK Badrinath1, K Nagarajan1, P Anand1, S Suresh Babu1, S Asmathulla2, M Mohammad Inaamul Hassan1
1 Department of General Medicine, Sri Manakula Vinayagar Medical College and Hospital, Puducherry, India
2 Department of Biochemistry, Sri Manakula Vinayagar Medical College and Hospital, Puducherry, India
|Date of Web Publication||28-Jun-2019|
Dr. M Mohammad Inaamul Hassan
C. 152, Kannadasan Street, Annanagar, Tennur, Trichy - 620 017, Tamil Nadu
Source of Support: None, Conflict of Interest: None
Background: Patients are treated with statins for the control of cholesterol; but statins control only low-density lipoprotein (LDL) and not non-high-density lipoprotein (non-HDL). Also, LDL is not a good coronary risk predictor. That creates the necessity to find a better biomarker for future coronary risk prediction. Hence, biomarkers under this territory such as total cholesterol (TC)/HDL, LDL/HDL, triglyceride (TG)/HDL ratios, non-HDL, apolipoprotein-B (apo-B), and high-sensitivity C-reactive protein (hs-CRP) were to be assessed and correlated with LDL to find the better biomarker in Indian patients.
Objective: The objective was to study non-HDL, apo-B, TC/HDL, TG/HDL, LDL/HDL ratios, and hs-CRP in patients under statin therapy; and to correlate them with their LDL; to predict the risk of future coronary events; and to identify which biomarker among them is better at detecting the same.
Materials and Methods: This is a cross-sectional observational study performed by systematic random sampling among 87 patients under statin therapy, and the levels of LDL, TC/HDL, LDL/HDL, TG/HDL ratios, non-HDL, apo-B, and hs-CRP were measured in such patients, and their correlation with optimized and unoptimized LDL groups were done. Continuous data were represented as mean and standard deviation, andP value was calculated using independent t-test or z-test.
Results: Non-HDL, TC/HDL, and LDL/HDL ratios were found to be statistically significant – all three parameters withP < 0.0001 in predicting the coronary artery disease attacks in the future.
Conclusion: Even though all patients in our study were under statin therapy, they are still under the risk of developing coronary events. This can be solved by targeting the control of non-HDL or TC/HDL or LDL/HDL ratios, as they are found be better biomarkers for future coronary risk prediction.
Keywords: Apolipoprotein-B, cholesterol, coronary artery disease, low-density lipoprotein, non-high-density lipoprotein, statin, total cholesterol/high-density lipoprotein, triglyceride/high-density lipoprotein, and low-density lipoprotein/high-density lipoprotein ratios
|How to cite this article:|
Badrinath A K, Nagarajan K, Anand P, Babu S S, Asmathulla S, Inaamul Hassan M M. Coronary risk prediction by the correlation of total cholesterol/high-density lipoprotein, triglyceride/high-density lipoprotein, low-density lipoprotein/high-density lipoprotein ratios, non-high-density lipoprotein, apolipoprotein-B, and high-sensitivity C-reactive protein with low-density lipoprotein in Indian patients under statin therapy. Heart India 2019;7:63-7
|How to cite this URL:|
Badrinath A K, Nagarajan K, Anand P, Babu S S, Asmathulla S, Inaamul Hassan M M. Coronary risk prediction by the correlation of total cholesterol/high-density lipoprotein, triglyceride/high-density lipoprotein, low-density lipoprotein/high-density lipoprotein ratios, non-high-density lipoprotein, apolipoprotein-B, and high-sensitivity C-reactive protein with low-density lipoprotein in Indian patients under statin therapy. Heart India [serial online] 2019 [cited 2019 Sep 23];7:63-7. Available from: http://www.heartindia.net/text.asp?2019/7/2/63/261833
| Introduction|| |
Asian Indians, whether living in India or elsewhere, have a higher incidence of developing coronary artery disease (CAD) when compared to other ethnic groups. There is an urgent need to put a hold to these increasing figures. Here is where statin therapy comes into play. However, statins control only low-density lipoprotein (LDL) and not non-high-density lipoprotein (non-HDL). Controlling just LDL would not help, as it cannot be considered a reliable biomarker for future coronary risk prediction. This has created a vacuum for identification of a reliable biomarker which could help in future coronary risk prediction. Total cholesterol (TC)/HDL, LDL/HDL, triglyceride (TG)/HDL ratios, non-HDL, apolipoprotein-B (apo-B), and high-sensitivity C-reactive protein (hs-CRP) are other biomarkers under this category which could help to analyze this risk. However, the better future coronary risk predictor among the above-mentioned markers had to be studied.
| Materials and Methods|| |
This is a cross-sectional observational study, with systematic random sampling done among a sample size of 87 patients of ages between 35 and 85 years old, who attended as outpatients to, or were inpatients of the Department of General Medicine in Sri Manakula Vinayagar Medical College and Hospital, Pondicherry, India; within a period of around 8 months, between December 2017 and July 2018. Informed written consent was obtained from all the participants, and the Institutional Ethics Committee approval was obtained for performing the study.
- Age <35 or >85 years of age
- Patients on irregular statin therapy
- Patients with chronic kidney disease
- Patients who have a poor left ventricular function.
Blood samples of around 6 mL were taken from the study group at presentation in ethylenediaminetetraacetic acid (EDTA) tubes obtained through antecubital venous access.
The TC, HDL, and TGs were measured after overnight fasting, using ChemWell 2910 autoanalyzer. Meanwhile, the LDL was measured using the Friedewald formula (LDL = TC – HDL– TG/5) which is internationally accepted. Apo-B was measured using Fine Test ELISA Kit, and hs-CRP was measured using Diagnostic Canada Inc., ELISA kit. Non-HDL was obtained by the deduction of HDL from TC. TC/HDL, LDL/HDL, and TG/HDL ratios were obtained from the above-mentioned results.
Data were entered into Microsoft Excel data sheet and were analyzed using SPSS version 22.0 (IBM SPSS Statistics, Somers NY, USA) software. Continuous data were presented as mean and standard deviation, and P value was calculated using independent t-test or z-test after assuming all the rules of statistical tests. Patients were divided into two groups – those with optimized LDL and unoptimized LDL. Biomarkers such as non-HDL, hs-CRP, apo-B, TC/HDL, TG/HDL, and LDL/HDL ratios were selected (based on the previous studies as biomarkers for coronary risk prediction) to be correlated with the two mentioned LDL groups in Indian patients to assess the better biomarker among them.
| Results|| |
A total of 87 patients were included in the study, among whom 62.1% had optimized LDL levels, and in the remaining 37.9%, LDL levels were not optimized [Table 1]. The mean age of the study group was 60.66 years. While 62.06% of the study group comprised males and 37.94% were females.
Non-HDL, TC/HDL ratio, and LDL/HDL ratio were found to be statistically significant; with all three parameters having P < 0.0001 in predicting the CAD attacks in the future.
The area under the receiver operating characteristic (ROC) curve [Figure 1] was found to be more for non-HDL-C when compared with other parameters and was found to be a better biomarker in prediction of future CAD. The area under the ROC curve for non-HDL-C, TC/HDL ratio, and TG/HDL ratio were found to be statistically significant in predicting CAD attacks in the future [Table 2].
|Figure 1: Receiver operating characteristic curve for predicting the outcome of coronary artery disease|
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|Table 2: Area under the curve for predicting the outcome of coronary artery diseases|
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On comparison of the non-HDL levels with LDL cholesterol levels, it was found that, a significant proportion of the patients despite having been on statin therapy, had high unoptimized LDL levels with high non-HDL levels (21.2% in the unoptimized LDL group had a non-HDL of borderline high and 6.1% of those in unoptimized LDL had a non-HDL of high), with a P < 0.0001, as seen in [Table 3].
|Table 3: Comparison of non-high-density lipoprotein with low-density lipoprotein cholesterol|
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When TC/HDL ratio was compared with LDL levels, it was found that, 76% of them with optimized LDL-C and 64% with an unoptimized LDL-C level had a moderately high level of TC/HDL ratio. Similarly, 3.9% of the patients with optimized LDL-C and 36% patients of the un-optimized LDL-C group had high levels of TC/HDL ratio. Moreover, these values were statistically significant with P < 0.0001, as shown in [Table 4].
|Table 4: Comparison of total cholesterol/high-density lipoprotein ratio with low-density lipoprotein cholesterol|
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As shown in [Table 5], the LDL/HDL ratio was also compared with LDL-C; and was found that, 32.1% of the patients with optimized LDL-C, and 51.7% of those with unoptimized LDL-C had a moderately high level of LDL/HDL ratio. Whereas, 3.8% of those with optimized LDL-C and 48.3% of those with unoptimized LDL-C had a high level of LDL/HDL. Even these values were statistically significant, with P < 0.0001.
|Table 5: Comparison of low-density lipoprotein/high-density lipoprotein ratio with low-density lipoprotein cholesterol|
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Gender-based analysis of LDL-C and non-HDL-C revealed the fact that both LDL-C and non HDL-C were found to be high in males, rather than in females; with a P value of 0.088 and 0.02, respectively; as depicted in [Figure 2] and [Figure 3].
|Figure 2: Gender-wise distribution of low-density lipoprotein cholesterol|
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|Figure 3: Gender-wise distribution of nonhigh-density lipoprotein cholesterol|
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The levels of hs-CRP, apo-B, and TG/HDL ratio were not statistically significant in helping assess the future coronary risk events, with P values of 0.441, 0.188, and 0.599, respectively, according to our study as shown in [Table 6], [Table 7], [Table 8], respectively.
|Table 6: Comparison of hs-C-reactive protein with low-density lipoprotein cholesterol|
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|Table 7: Comparison of apo-B levels with low-density lipoprotein cholesterol|
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|Table 8: Comparison of triglyceride/high-density lipoprotein ratio with low-density lipoprotein cholesterol|
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| Discussion|| |
Cardiovascular disease accounts for approximately 17.5 million deaths annually, and of these, 7.6 million are attributed to CAD and 5.7 million to stroke. In India, the incidence of CAD has doubled in the past 25 years. There is an urgent need to put a hold to these increasing figures. Here is where the statin therapy comes into play. However, statin therapy controls only that of LDL-C and not non-HDL-C.
As plasma TG concentration increases, as in patients with diabetes mellitus, the very-low-density lipoproteins (VLDL) composition is altered, and the estimation of LDL-C concentration becomes progressively less accurate. Furthermore, at present, the concentration of LDL-C is estimated using the Friedewald equation: LDL-C = TC-HDLC-TG/5 mg/dL. The third adult treatment panel of the National Cholesterol Education Program had issued revised guidelines for the treatment of cholesterol in adults published in May 2001. Increased attention to the metabolic syndrome and diabetes, including the inaccuracy of the LDL-C measurement in these patients because of elevated TGs was highlighted. According to a study conducted by Thanassoulis et al., statin was more closely related to reductions in apo-B than to reductions in either non-HDL or LDL.
Using the Friedewald equation for LDL, ignores the important atherogenic VLDL remnants as targets for therapy. Meanwhile, the VLDL remnants, as well as the atherogenic IDL, LDL, and TGs, are accounted for using the simple non-HDL calculation which is TC – HDL. Non-HDL incorporates all cholesterol in potentially atherogenic lipoprotein particles, VLDL, IDL, LDL, and lipoprotein (a). Another study conducted by Boekholdt et al. concluded that changes in non-HDL-C also explained a larger proportion of the atheroprotective effect of statin intervention than did LDL cholesterol and apo-B.
Although it was previously believed that LDL was the most atherogenic lipoprotein and thus became the target for therapy surveillance, it is now realized that all of these lipoproteins confer some atherogenic potential. The total apo-B level indicates the total number of lipoprotein particles in LDL, IDL, and VLDL. Since most apo-B containing particles are atherogenic, it was hypothesized that the total apo-B concentration should be a better predictor of coronary heart disease (CHD) risk than LDL according to earlier studies.
A few other studies have shown that a high LDL/HDL ratio with a high TG level has the highest CHD development risk. But because the measurement of VLDL is missed when just this (ratio of LDL/HDL and measurement of high TG) is done in patients with high VLDL with elevated triglycerides, a mere measurement of LDL/HDL ratio may not be accurate, and so the TC/HDL ratio was studied for, and was found to be a better predictor for identifying risk of development of ischemic heart disease.
Whereas, a few other studies showed that, the abnormal ratio of TG/HDL was found to be the single most powerful predictor of extensive CHD among all the lipid variables examined. In a study conducted by Ray et al., the analysis of acute coronary syndrome patients receiving statin therapy apo-B/AI, TC/HDL ratios, non-HDL, and LDL all provided similar information on risk prediction, however, the addition of hs-CRP to lipid-based measurements significantly improved the risk prediction.
Most of these studies were not done in India. As most of the aforementioned studies were done in the West, and as the Indian diet varies drastically from the diet of that of the Western world, and an Indian study is necessary at this juncture to assess the better biomarker which could help for the coronary risk prediction among TC/HDL, LDL/HDL, TG/HDL ratios, non-HDL, and apo-B. This study was carried out with this intent.
In our study, we found that both the TC/HDL and LDL/HDL ratios were found to be reliable in predicting the future coronary risk; as they uncovered the future coronary risk even in patients with optimized LDL-C. Non-HDL-C levels were also helpful in detecting future coronary risk; albeit with a lesser reliability. However, other parameters such as apo-B, hs-CRP, and TG/HDL ratio were not statistically significant in detecting the future coronary events.
| Conclusion|| |
Based on our study, what we propose is, to assess a patient's future coronary risk prediction, measurement of LDL-C alone is insufficient. It is best to measure his/her TC/HDL ratio or LDL/HDL ratio or non-HDL-C levels to detect the future coronary risk and to target and control these parameters to reduce any coronary risk development in the future.
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Conflicts of interest
There are no conflicts of interest.
| References|| |
Ardeshna DR, Bob-Manuel T, Nanda A, Sharma A, Skelton WP 4th
, Skelton M, et al.
Asian-Indians: A review of coronary artery disease in this understudied cohort in the United States. Ann Transl Med 2018;6:12.
Lim SY. Role of statins in coronary artery disease. Chonnam Med J 2013;49:1-6.
Master SR, Rader DJ. Beyond LDL cholesterol in assessing cardiovascular risk: Apo B or LDL-P? Clin Chem 2013;59:723-5.
Institute of Medicine (US) Committee on Preventing the Global Epidemic of Cardiovascular Disease: Meeting the Challenges in Developing Countries. Epidemiology of Cardiovascular Disease. In: Fuster V, Kelly BB, editors. Promoting Cardiovascular Health in the Developing World: A Critical Challenge to Achieve Global Health. Washington (DC): National Academies Press (US); 2010. p. 2. Available from: https://www.ncbi.nlm.nih.gov/books/NBK45688/
. [Last accessed on 2017 Feb 15].
Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive summary of the third report of the national cholesterol education program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult treatment panel III). JAMA 2001;285:2486-97.
Thanassoulis G, Williams K, Ye K, Brook R, Couture P, Lawler PR, et al.
Relations of change in plasma levels of LDL-C, non-HDL-C and apoB with risk reduction from statin therapy: A meta-analysis of randomized trials. J Am Heart Assoc 2014;3:e000759.
Frost PH, Havel RJ. Rationale for use of non-high-density lipoprotein cholesterol rather than low-density lipoprotein cholesterol as a tool for lipoprotein cholesterol screening and assessment of risk and therapy. Am J Cardiol 1998;81:26B-31B.
Boekholdt SM, Arsenault BJ, Mora S, Pedersen TR, LaRosa JC, Nestel PJ, et al.
Association of LDL cholesterol, non-HDL cholesterol, and apolipoprotein B levels with risk of cardiovascular events among patients treated with statins: A meta-analysis. JAMA 2012;307:1302-9.
Masson W, Siniawski D, Lobo M, Molinero G, Giorgi M, Huerín M. Association between LDL-C, non HDL-C, and apolipoprotein B levels with coronary plaque regression. Arq Bras Cardiol 2015;105:11-9.
Lemieux I, Lamarche B, Couillard C, Pascot A, Cantin B, Bergeron J, et al.
Total cholesterol/HDL cholesterol ratio vs. LDL cholesterol/HDL cholesterol ratio as indices of ischemic heart disease risk in men: The Quebec cardiovascular study. Arch Intern Med 2001;161:2685-92.
da Luz PL, Favarato D, Faria-Neto JR Jr., Lemos P, Chagas AC. High ratio of triglycerides to HDL-cholesterol predicts extensive coronary disease. Clinics (Sao Paulo) 2008;63:427-32.
Ray KK, Cannon CP, Cairns R, Morrow DA, Ridker PM, Braunwald E, et al.
Prognostic utility of apoB/AI, total cholesterol/HDL, non-HDL cholesterol, or hs-CRP as predictors of clinical risk in patients receiving statin therapy after acute coronary syndromes: Results from PROVE IT-TIMI 22. Arterioscler Thromb Vasc Biol 2009;29:424-30.
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8]