|Year : 2021 | Volume
| Issue : 1 | Page : 72-76
The role of triglycerides and triglyceride/high-density lipoprotein ratio as a positive predictive factor in peripheral vascular disease
Rajendra Prasad Basavanthappa, Nivedita Mitta, Sanjay C Desai, Chandrashekar Anagavalli Ramswamy, J P Vivek Vardhan, Ashwini Naveen Gangadharan, Ranjith Kumar Anandasu, Adharsh Kumar Maruthu Pandian, R Hemanth Kumar Chowdary
Department of Vascular Surgery, Ramaiah Medical College, Bengaluru, Karnataka, India
|Date of Submission||07-Nov-2020|
|Date of Acceptance||07-Dec-2020|
|Date of Web Publication||20-Feb-2021|
Department of Vascular Surgery, Ramaiah Medical College, Bengaluru, Karnataka
Source of Support: None, Conflict of Interest: None
Background: High triglycerides (TG) and low High density Lipoproteins (HDL) are established coronary risk predctors (ratio of 3:1 being associated with definite increase in coronary risk). The TG/HDL ratio has also been established as a predictor of major cardio vascular events, insulin resistance and metabolic syndrome. However, the utility of the same in predicting worsening of peripheral vascular disease remains under-researched. Aims and Objectives: We aim at establishing TG/HDL ratio as a predictor of peripheral arterial disease in diabetic patients and to also explore the role of triglycerides and lipid lowering agents, in general, in modifying this risk. Materials and Methods: We carried out a cross sectional study enrolling Diabetes Mellitus patients with symptoms suggestive of peripheral vascular disease. We included 304 patients and analyzed their TG levels and TG/HDL ratios stratified as per age, gender and medical history. Relevant statistical analysis was carried out. Results: There was a difference in TG levels in men and women who developed serious peripheral vascular events with women having significantly elevated TG levels in comparison to men. The TG/HDL ratio was also found to be 8.06 in women and 7.88 in men. This was statistically significant in comparison to the control group. Conclusion: TG/HDL-C ratio, also known as atherogenic index, which is easily obtained by routine biochemical evaluation can be used to prognosticate incidence of peripheral arterial disease in addition to cardiovascular risk. This would serve as an easy Outpatient prognosticating and predictive factor for further assessment and patient education.
Keywords: Statins, triglyceride/high-density lipoprotein ratio, triglycerides
|How to cite this article:|
Basavanthappa RP, Mitta N, Desai SC, Ramswamy CA, Vardhan J P, Gangadharan AN, Anandasu RK, Maruthu Pandian AK, Kumar Chowdary R H. The role of triglycerides and triglyceride/high-density lipoprotein ratio as a positive predictive factor in peripheral vascular disease. Indian J Vasc Endovasc Surg 2021;8:72-6
|How to cite this URL:|
Basavanthappa RP, Mitta N, Desai SC, Ramswamy CA, Vardhan J P, Gangadharan AN, Anandasu RK, Maruthu Pandian AK, Kumar Chowdary R H. The role of triglycerides and triglyceride/high-density lipoprotein ratio as a positive predictive factor in peripheral vascular disease. Indian J Vasc Endovasc Surg [serial online] 2021 [cited 2021 Feb 25];8:72-6. Available from: https://www.indjvascsurg.org/text.asp?2021/8/1/72/309702
| Introduction|| |
An abnormal triglyceride to high-density lipoprotein ratio (TG/HDL) has proved to be a useful guideline in predicting cardiovascular risk and insulin resistance. Its application is well known in coronary disease prognostication, but research is ongoing on its application in peripheral vascular and carotid disease. We attempt to utilize the same ratio in predicting and correlating with peripheral arterial disease in our center.
One of the most common causes of lower extremity peripheral artery disease (PAD) is a systemic atherosclerotic process. Although the disease is mostly seen in males, the incidence is rising among women. Multiple segment involvement is seen in the same patient. It is important to diagnose early and determine the disease extent for planning treatment in case of clinical suspicion. In addition to age and diabetes mellitus (DM), hyperlipidemia is one of the known risk factors of atherosclerosis. Increased TG and decreased HDL values increase atherosclerosis risk and hence, TG/HDL ratio is an atherogenic index. It has shown to predict the presence of disease in those who underwent coronary angiography. Several studies have shown a strong association between total cholesterol, low-density lipoprotein (LDL), or low HDL and the incidence of atherosclerosis-related diseases, such as ischemic heart disease and stroke., As of recent research, lipid particle subfractions have been implicated in the atherogenic process. Small dense LDL particles are more atherogenic than the larger buoyant ones, and different HDL subfractions play varied roles in atherogenesis. The larger, less dense HDL2 particles are found to be protective, while the small dense HDL3 particles are considered atherogenic., The former correlates inversely with serum TGs and small dense LDL. The ratio of TGs to HDL-cholesterol ratio (TG/HDL) correlates inversely with the plasma level of small, dense LDL particles.
Aim of the study
We analyzed the relationship between serum lipids and the development of PAD as manifested by claudication, positive low ankle-brachial index (ABI), or significant obstructive lesions in peripheral angiograms, wherever available. A large series of studies shows that a TG/HDL ratio of >2 was associated with moderate cardiovascular risk and anything >4 is the most powerful independent predictor of carotid artery disease development. Thus, this ratio shows promise as an attractive supportive index of the atherogenicity. However, limited information exists about the association between TG/HDL ratio and severity of lesions in PAD. The aim of the present study was to study the role of the TG/HDL ratio in predicting the incidence of PAD as a positive predictor.
| Materials and Methods|| |
We conducted a cross-sectional study in the Department of Vascular and Endovascular Surgery, MS Ramaiah Medical College, Bangalore. Patients who were diagnosed with or referred to us with suspicion of PAD and presented to our department between September 2019 and October 2020 were included in this study. All demographic data (age, gender, comorbidities, etc.,) and routine blood tests were obtained. Our inclusion criteria were patient age >18 years of age, ABI >0.7, and consenting to participate in our study. Exclusion criteria were patients with familial hyperlipidemia, critical limb ischemia, vasculitis, systemic inflammatory diseases, and a previous intervention due to PAD. A total of 624 patients were included. The patients consisted mostly of claudicants and were referred to the vascular surgery team for evaluation and intervention. Of these, 304 patients fit into our inclusion criteria and were taken as subjects in the positive/symptomatic group. The patient demography is shown in [Table 1].
The presence of risk factors was defined as shown in [Table 2].
|Table 2: Risk factors used to describe patients at high risk for developing peripheral arterial disease in terms of biochemical factors|
Click here to view
Laboratory tests for total cholesterol and fractions, TGs, and glycemia were performed using standard techniques.
Statistical analysis SPSS 21.0 (IBM Statistical Package for the Social Sciences Statistic Inc., version 21.0, Chicago, IL, USA) was used for the statistical analysis of data. Mean and standard deviations were calculated using descriptive methods for continuous and ordinal data. Data were compared with Chi-square test. P < 0.05 was considered statistically significant.
| Results|| |
The patients (n = 302) who met our inclusion criteria were part of Group 1 and we collected data of about 320 patients who did not have any signs of peripheral arterial disease and were matched for all variables analyzed. This group constituted Group 2 which was used as a cohort for comparison with our study group. All our patient demographics were comparable with no significant difference in both the groups [Table 2].
In Group 1, the average age of our patients was 64 ± 6 years and the study group was predominantly male (87.7%) in comparison to 80.6% male in the comparison group. The groups were comparable for DM, hypertension, and renal function. However, there was a significant difference in the body mass index (BMI) of both groups with the BMI in the study group being 31.95 in comparison to 26.7. This could probably be due to the fact that obesity and BMI are both, a cause and an indicator of, insulin resistance and dyslipidemia.
The use of medication (statins and aspirin) was comparable in both the groups. However, the percentage of use of statins and aspirin was higher in women in comparison to men in the symptomatic group. Of notice is the fact that the TG levels were significantly higher in women in comparison to men in Group 1. The other lipid parameters were also higher in women but were not statistically significant [Chart 1].
In terms of lipid parameters measured, there was a significant difference in the values of cholesterol, LDL, and TGs as shown in [Table 3]. Specifically, with regards to the levels of serum cholesterol and TG as indicated by a significant P value of P < 0.05. There is also a significant difference in the TG/HDL ratios in both groups. The ratio is higher in the female subgroup in both the groups and significantly higher in the symptomatic groups, i.e., 8.06 versus 7.88 in men. The same ratio in the asymptomatic group is 5.98 versus 4.98 in the asymptomatic group.
The mean in the symptomatic group was 7.88 ± 0.21 and 8.06 ± 0.18 in men and women, respectively (while it was 5.98 ± 0.32 and 4.98 ± 0.22 in the asymptomatic group). This was statistically significant and could be used as a probable cutoff value as an indication of development or worsening peripheral arterial disease.
| Discussion|| |
The role of blood lipid parameters in the pathophysiology of atherosclerosis is well established. The increase in blood lipid values contributes to the atherosclerotic process, except for HDL, which plays a protective role against the disease. TG/HDL ratio is known to predict the extent of atherosclerosis more sensitively compared to any one blood lipid parameter. Arterial disease of the lower extremities is increasing in incidence and can be detected in 3%–12% of the population. Blood lipid parameters are important in the development of atherosclerotic peripheral arterial disease. According to Tanriverdi and Savas Tetik, dyslipidemia was found to be sufficient for the development of atherosclerosis, even in the absence of other risk factors.
Low HDL values are known to be associated with increased cardiovascular risk. Increased TG is also an established risk factor for atherosclerosis. Prospective studies show that 38.6 mg/dl increase in TG may increase the risk of cardiovascular disease by >50%, independent of HDL in a 10-year follow-up period. Arterial stiffness is a condition that arises with the onset of atherosclerosis and this further increases mortality due to cardiovascular disease. Da Luz et al. and Zhan et al. detected that increased TG/HDL ratio was correlated with PAD.
The atherogenic property of high TGs and HDL is due to the higher plasma concentration of TG-rich, very LDL which creates small, dense LDL during lipid exchange and lipolysis. These LDL particles remain in the circulation and form small, dense HDL particles, undergo accelerated catabolism, and eventually closing the atherogenic circle.,
The findings of the present study are in line with most studies with respect to the age of presentation and gender distribution. However, a point of note is the fact that women in our study groups had a statistically significant higher level of TGs when symptomatic in comparison to men. This is in line with the findings of Prasad et al. in their analysis of the same in coronary disease. This mandates further study in this direction in order to assess the effect of TGs by themselves in women and also to investigate the much higher TG/HDL ratio noted in women overall than in men. Another observation is that in the same subjects, the cholesterol levels were not significantly elevated when compared to the asymptomatic group or the men in either groups. This is a unique finding as it may mandate the addition of not only statins in these women but also of fibrates.
With respect to the use of medication in these patients, almost half of the symptomatic women were on antiplatelets and a third were on statins. This could be attributed to probable association of cardiac comorbidities in these women and again substantiates the probable need for fibrates to target the triglyceridemia. Moreover, menopausal status and aging probably play a major role in linking increased TG levels to increased cardiovascular risk. Another point in favor of additional antilipid treatment is that a third of the patients had deranged TGs inspite of being on statins.
However, the most important observation is the fact that though a TG/HDL ratio of 1 or less is desirable and between 2 and 4 is associated with an increased risk of cardiovascular morbidity and mortality, the ratio seems to be higher in case of peripheral vascular disease as per our study. We observed that the incidence of peripheral vascular occurred in patients with TG/HDL ratio of >7.5. This could probably act as a simple outpatient test to stratify the risk in a patient for developing peripheral vascular disease. The ratio seemed to be higher in women but could be attributed to the higher TG levels.
The strength of the study lies in that it is a novel study in a population known to have prevalent metabolic syndrome, diabetes, and insulin resistance. All these conditions are detectable with the TG/HDL ratio and the same can be utilized in prognosticating the patient of an impending peripheral vascular event at a ratio higher than that considered a risk for cardiac events.
There are some limitations that must be considered. These findings are based on cross-sectional data, potentially limiting validity. While baseline use of statins is known, no further details on dose, adequacy, etc., and lifestyle habits are available. In addition, another important limitation to consider is that angiographic evaluation for most patients was not done as a majority were claudicants only. These limitations highlight the need for a wider range, prospective study with stress on treatment intervention to further understand the role of TGs and statin use in predicting outcomes.
| Conclusion|| |
TG/HDL-C ratio, also known as atherogenic index, which is easily obtained by routine biochemical parameters can be used to prognosticate incidence of peripheral arterial disease in addition to cardiovascular risk. However, the threshold seems to be much higher in case of the former.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Murguía-Romero M, Jiménez-Flores JR, Sigrist-Flores SC, Espinoza-Camacho MA, Jiménez-Morales M, Piña E, et al
. Plasma triglyceride/HDL-cholesterol ratio, insulin resistance, and cardiometabolic risk in young adults. J Lipid Res 2013;54:2795-9.
Karabay O, Karacelik M, Yilik L, Tekin N, Iriz AB, Kumdereli S, et al. Ischemic peripheral arterial disease: A screening survey. Turk Gogus Kalp Damar Cerrahisi Dergisi 2012;20:450-7.
Mukherjee D, Eagle K. The importance of early diagnosis and treatment in peripheral arterial disease: Insights from the PARTNERS and REACH registries. Curr Vasc Pharmacol 2010;8:293-300.
Harky A, Maskell P, Burgess M. Anti-platelet and anti-coagulant therapy in peripheral arterial disease prior to surgical intervention. Vascular 2019;27:299-311.
Frohlich J, Dobiásová M. Fractional esterification rate of cholesterol and ratio of triglycerides to HDL-cholesterol are powerful predictors of positive findings on coronary angiography. Clin Chem 2003;49:1873-80.
Ren X, Chen ZA, Zheng S, Han T, Li Y, Liu W, et al.
Association between triglyceride to HDL-C ratio (TG/HDL-C) and insulin resistance in Chinese patients with newly diagnosed type 2 diabetes mellitus. PLoS One 2016;11:e0154345.
Kiyosue A. Nonfasting TG/HDL-C ratio seems a good predictor of MACE in CAD patients with statin therapy. Could it be a treatment target? J Cardiol 2018;71:8-9.
Miller NE. Associations of high-density lipoprotein subclasses and apolipoproteins with ischemic heart disease and coronary atherosclerosis. Am Heart J 1987;113:589-97.
Robinson D, Ferns GA, Bevan EA, Stocks J, Williams PT, Galton DJ, et al.
High density lipoprotein subfractions and coronary risk factors in normal men. Arteriosclerosis 1987;7:341-6.
Williams PT, Krauss RM, Vranizan KM, Stefanick ML, Wood PD, Lindgren FT, et al.
Associations of lipoproteins and apolipoproteins with gradient gel electrophoresis estimates of high density lipoprotein subfractions in men and women. Arterioscler Thromb 1992;12:332-40.
Hokanson JE, Austin MA. Plasma triglyceride level is a risk factor for cardiovascular disease independent of high-density lipoprotein cholesterol level: A meta-analysis of population-based prospective studies. J Cardiovasc Risk 1996;3:213-9.
Salazar MR, Carbajal HA, Espeche WG, Leiva Sisnieguez CE, Balbín E, Dulbecco CA, et al.
Relation among the plasma triglyceride/high-density lipoprotein cholesterol concentration ratio, insulin resistance, and associated cardio-metabolic risk factors in men and women. Am J Cardiol 2012;109:1749-53.
Shammas NW. Epidemiology, classification, and modifiable risk factors of peripheral arterial disease. Vasc Health Risk Manag 2007;3:229-34.
Tanriverdi B, Savas Tetik S. Pathophysiology of the atherosclerosis and risk factors. Marmara Pharm J 2017;21:1-9.
Okamura T, Hayakawa T, Kadowaki T, Kita Y, Okayama A, Ueshima H. NIPPON DATA90 Research Group. The inverse relationship between serum high-density lipoprotein cholesterol level and all-cause mortality in a 9.6-year followup study in the Japanese general population. Atherosclerosis 2006;184:143-50.
Wen JH, Zhong YY, Wen ZG, Kuang CQ, Liao JR, Chen LH, et al.
Triglyceride to HDL-C ratio and increased arterial stiffness in apparently healthy individuals. Int J Clin Exp Med 2015;8:4342-8.
Boutouyrie P, Tropeano AI, Asmar R, Gautier I, Benetos A, Lacolley P, et al.
Aortic stiffness is an independent predictor of primary coronary events in hypertensive patients: A longitudinal study. Hypertension 2002;39:10-5.
da Luz PL, Favarato D, Faria-Neto JR, Jr., Lemos P, Chagas AC. High ratio of triglycerides to HDL-cholesterol ratio predicts extensive coronary disease. Clinics (Sao Paulo) 2008;63:427-32.
Zhan Y, Yu J, Ding R, Sun Y, Hu D. Triglyceride to high density lipoprotein cholesterol ratio, total cholesterol to high density lipoprotein cholesterol ratio and low ankle brachial index in an elderly population. Vasa 2014;43:189-97.
Packard CJ, Shepherd J. Lipoprotein heterogenity and apolipoprotein B metabolism. Arterioscler Thromb Vasc Biol 1999;19:2456-64.
Brinton EA, Eeisenberg S, Breslow JL. Increased apo A-I and apo-AII fractional catabolic rate in patients with low high density lipoprotein-cholesterol levels with or without hypertriglyceridemia. J Clin Invest 1991;87:536-44.
Prasad M, Sara J, Widmer RJ, Lennon R, Lerman LO, Lerman A. Triglyceride and triglyceride/HDL (high density lipoprotein) ratio predict major adverse cardiovascular outcomes in women with non-obstructive coronary artery disease. J Am Heart Assoc 2019;8:e009442.
Carr MC. The emergence of the metabolic syndrome with menopause. J Clin Endocrinol Metab 2003;88:2404-11.
[Table 1], [Table 2], [Table 3]