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Abstract

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Discussion
  6. Conclusion
  7. References

An elevated triglyceride (TG)/high-density lipoprotein (HDL) ratio has been described as a predictor of insulin resistance and cardiovascular events. We evaluated whether a TG/HDL ratio ≥3.5 was associated with the burden of coronary artery disease (CAD) on cardiac catheterization. A retrospective chart review of 156 consecutive adults presenting to the Montefiore Medical Center Emergency Department with symptoms of unstable angina and no known history of CAD who underwent cardiac catheterization as part of their index hospitalization was performed. TG and HDL data were available in 100 patients within 6 months prior to admission and no more than 24 hours after presentation. A priori, a burden of CAD score was developed. On multivariate analysis, a TG/HDL ratio ≥3.5 was associated with the burden of CAD (odds ratio, 2.87; 95% confidence interval, 1.03–7.96; p=0.04). Further study is warranted.

An elevated triglyceride (TG)/high-density lipoprotein (HDL) ratio has been described as a predictor of both insulin resistance1 and increased risk of cardiovascular events.2,3 We examined whether this ratio was associated with the burden of coronary artery disease (CAD) on cardiac cath eterization in consecutive adult patients presenting to the Montefiore Medical Center Emergency Department with symptoms of unstable angina and no known history of CAD who underwent cardiac catheterization as part of their index hospitalization.

Methods

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Discussion
  6. Conclusion
  7. References

We performed a retrospective chart review of 156 consecutive adult patients presenting to the Montefiore Medical Center Emergency Department beginning on January 1, 2002, with symptoms of unstable angina and no known history of CAD who underwent cardiac catheterization as part of their index hospitalization. We chose a TG/HDL ratio cutoff of ≥3.5 at the outset, as this cutoff has been described as a predictor of insulin resistance.1 TG and HDL data were available in 100 patients within 6 months prior to hospital admission and no more than 24 hours after presentation to the Emergency Department. No known CAD was defined as no known history of myocardial infarction, percutaneous coronary intervention, or coronary artery bypass surgery. Additional exclusion criteria were: 1) cardiac catheterization within the previous 6 months; 2) serum creatinine >3.0 mg/dL or hemodialysis; 3) New York Heart Association functional class III or IV; and 4) other severe acute illness or organ failure. Admission history and laboratory data were obtained. Creatinine clearance was calculated using the Cockcroft-Gault formula. Hyperlipidemia was defined as a history of hyperlipidemia or antihyperlipidemic medication use. Diabetes was defined as a history of diabetes or antihyperglycemic medication use. Smoking was defined as any history of tobacco smoking. Hypertension was defined as a history of hypertension or antihypertensive medication use. The Montefiore Medical Center Institutional Review Board approved this study.

A priori, a burden of CAD score was developed with higher values representing a greater burden of CAD. We scored the burden of CAD as follows: 1) left main coronary artery: each individual stenosis of 20%–49% was given a score of 0.5; 50%–69%, 1.0; and ≥70%, 1.5, respectively; 2) left anterior descending artery system (which included the left anterior descending and diagonals): each individual stenosis of 20%–49% was given a score of 0.5; 50%–69%, 1.0; and ≥70%, 1.5, respectively; 3) left circumflex system (which included the left circumflex and obtuse marginals): each individual stenosis of 20%–49% was given a score of 0.5; 50%–69%, 1.0; and ≥70%, 1.5, respectively; and 4) right coronary artery system (which included the right coronary artery, posterior descending artery, and posterior left ventricular branches): each individual stenosis of 20%–49% was given a score of 0.5; 50%–69%, 1.0; and ≥70%, 1.5, respectively. If a ramus branch was present, each individual stenosis of 20%–49% was given a score of 0.25; 50%–69%, 0.5; and ≥70%, 0.75, respectively. The percentages of stenoses were obtained from official catheterization reports from one of two experienced interventional cardiologists. The score for each individual lesion was totaled into an overall burden of CAD score. The scoring system was considered “appropriate” by three independent cardiologists.

Given that the CAD burden score was nonnormally distributed, as it was skewed to the right, a cutoff at the 50th percentile of the CAD burden score was made to dichotomize the data. t tests and Chi-square analysis were performed when comparing means and proportions of baseline measurements between subjects with a TG/HDL ratio <3.5 and ≥3.5 and between subjects with CAD burden above and below the 50th percentile, respectively. To evaluate the relationships between the TG/HDL ratio and CAD burden, univariate analyses and multivariate analyses adjusting for baseline characteristics were conducted using logistic regression models. All statistical analysis was performed with the MDAS Version 2.0 (esKay Software, Pittsburgh, PA) statistical software package.

Results

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Discussion
  6. Conclusion
  7. References

Baseline characteristics are presented in Table I. Subjects with a TG/HDL ratio ≥3.5 were significantly more likely to smoke.

Table I.  Baseline Patient Characteristics
 Overall (N=100)TG/HDL <3.5 (n=68)TG/HDL≥3.5 (n=32)p Value*
Age (yr)60.4±12.961.5±12.658.1±13.4NS
Male52.051.553.1NS
Creatinine clearance (mL/min)100.5±68.893.6±38.1115.0±108.0NS
Diabetes29.027.931.3NS
Body mass index (kg/m2)28.2±5.327.7±5.429.0±5.2NS
Hypertension72.072.171.9NS
Dyslipidemia41.0**36.851.6**NS
Smoking29.025.840.60.01
Data are presented as mean ± SD or %. TG/HDL=triglyceride/high-density lipoprotein ratio; NS=nonsignificant; *p<0.05 was considered significant; **one patient missing; six patients missing

Baseline characteristics for the dichotomized CAD burden variable are presented in Table II. The CAD burden score range was 0–19, with a 50th percentile of 2.5. Subjects with a CAD burden score ≥50th percentile were significantly older.

Table II.  Baseline Patient Characteristics by Dichotomized CAD Burden Score
 CAD Burden Score By Percentile 
 <50th (n=50)≥50th (n=50)p Value*
Age (yr)56.2±12.864.5±11.7<0.01
Male48.056.0NS
Creatinine clearance (mL/min)104.8±44.996.1±86.7NS
Diabetes36.022.0NS
Body mass index (kg/m2)29.1±6.127.2±4.3NS
Hypertension74.070.0NS
Dyslipidemia42.040.8**NS
Smoking26.5**35.6NS
TG/HDL ≥3.526.038.0NS
Data are presented as mean ± SD or %. CAD=coronary artery disease; NS=nonsignificant; TG/HDL=triglyceride/high-density lipoprotein ratio; *p<0.05 was considered significant; **one patient missing; five patients missing

On univariate analysis, the TG/HDL ratio was not significantly associated with the burden of CAD (odds ratio [OR], 1.74; 95% confidence interval [CI], 0.73– 4.16; p=0.20). On multivariate analysis, including age, sex, creatinine clearance, body mass index, history of diabetes, hypertension, smoking, and hyperlipidemia, the TG/HDL ratio was significantly associated with the burden of CAD (OR 2.87; 95% CI, 1.03–7.96; p=0.04).

Discussion

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Discussion
  6. Conclusion
  7. References

We found that the serum ratio of TG/ HDL ≥3.5 is associated with an increased burden of CAD on cardiac catheterization during an index hospitalization in patients who presented with symptoms of unstable angina and without known cardiovascular disease when controlling for comorbidities. To the best of our knowledge, this study is the first to demonstrate this association.

Furthermore, this association was present when controlling for a history of diabetes. This finding supports the theme of increasing risk as a subject progresses from a normoglycemic state to one of insulin resistance.4,5

Insulin resistance has been associated with an increased risk of coronary events, and the TG/HDL ratio has been proposed as a marker of insulin resistance.1 The mechanism by which insulin resistance may increase cardiovascular risk is complex. At the endothelial level, insulin resistance alters the activation of intracellular signaling pathways. These events lead to decreases in endothelial nitric oxide production, increases in endothelin production, stimulation of the transcription of proinflammatory genes, and an increased tendency to coagulate.6 Our findings support the relationship among insulin resistance, TG/HDL ratio, and CAD.

Our study is limited by being a retrospective analysis. In addition, only 100 of the 156 subjects included in the study had available lipoprotein measurements. Furthermore, our measure of the burden of CAD, although deemed “appropriate” by three independent cardiologists, has not been validated. Previous studies, however, have utilized a similar scale in grading coronary artery lesions based on angiographic findings.7,8

Conclusion

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Discussion
  6. Conclusion
  7. References

We found that a TG/HDL ratio ≥3.5 is associated with an increased burden of CAD on cardiac catheterization in subjects with symptoms of unstable angina and no known history of CAD when controlling for comorbidities. Further study is warranted to explore this association.

References

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Discussion
  6. Conclusion
  7. References
  • 1
    McLaughlin T, Reaven G, Abbasi F, et al. Is there a simple way to identify insulin-resistant individuals at increased risk of cardiovascular disease? Am J Cardiol. 2005;96:399404.
  • 2
    Jeppesen J, Hein HO, Suadicani P, et al. Relation of high TG-low HDL cholesterol and LDL cholesterol to the incidence of ischemic heart disease. An 8-year follow-up in the Copenhagen Male Study. Arterioscler Tromb Vasc Biol. 1997;17:11141120.
  • 3
    Gaziano JM, Hennekens CH, O'Donnell CJ, et al. Fasting triglycerides, high-density lipoprotein, and risk of myocardial infarction. Circulation. 1997;96:25202525.
  • 4
    Sheu WH, Jeng CY, Young MS, et al. Coronary artery disease risk predicted by insulin resistance, plasma lipids, and hypertension in people without diabetes. Am J Med Sci. 2000;319(2):8488.
  • 5
    Saely CH, Aczel S, Marte T, et al. The metabolic syndrome, insulin resistance, and cardiovascular risk in diabetic and nondiabetic patients. J Clin Endocrinol Metab. 2005;90:56985703.
  • 6
    Montagnani M, Golovchenko I, Kim I, et al. Inhibition of phosphatidylinositol 3-kinase enhances mitogenic actions of insulin in endothelial cells. J Biol Chem. 2002;277:17941799.
  • 7
    Mark DB, Nelson CL, Califf RM, et al. Continuing evolution of therapy for coronary artery disease. Circulation. 1994;89:20152025.
  • 8
    O'Connor CM, Velazquez EJ, Gardner LH, et al. Comparison of coronary artery bypass grafting versus medical therapy on long-term outcome in patients with ischemic cardiomyopathy (a 25-year experience from the Duke Cardiovascular Disease Databank). Am J Cardiol. 2002;90:101107.