ISSN 2415-3060 (print), ISSN 2522-4972 (online)
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JMBS 2020, 5(1): 125–134
https://doi.org/10.26693/jmbs05.01.125
Clinical Medicine

Peculiarities of Clinical Presentations and Long–Term Complications in Patients with Coronary Artery Disease and Metabolic Syndrome, depending on their Serum Triglyceride Levels

Korolyuk O. Ya.
Abstract

Hypertriglyceridemia is the second most common, although non–mandatory, criterion of metabolic syndrome. Despite the growing body of evidence about its independent impact on cardiovascular risk and mortality, currently this dyslipidemia is considered to be a factor of residual risk after low density lipoprotein (LDL) cholesterol and non-high density lipoprotein cholesterol. The purpose of the study was to elucidate peculiarities of clinical manifestations, metabolic disorders, and long–term cardiovascular complications in patients with coronary artery disease and metabolic syndrome. Materials and methods: totally 107 patients with established coronary artery disease and ≥ 3 criteria of metabolic syndrome underwent anthropometry, transthoracic echocardiography, abdominal ultrasonography, and laboratory tests, including lipid profile, HbA1c, and oral glucose tolerance test with parallel detection of serum insulin and C–peptide levels and calculation of insulin sensitivity indices. According to serum triglyceride levels <1.7 and ≥1.7 mmol/L patients were divided into group 1 (n=49, 28 men, 21 women) and group 2 (n=58 with mail–to–female ratio 1:1; 35 cases of mild and 23 cases of moderate hypertriglyceridemia). Fisher’s exact test or Mann–Whitney U–test was used to compare the groups. The survival was analyzed by Kaplan–Meier’s method with calculation of cumulative proportion surviving, using Cox’s F–test for comparison; p values <0.05 were considered significant. Results and discussion. The prevalence of atrial fibrillation and atrioventricular regurgitation was more common among group 1 patients (24.5% vs. 10.3%, p=0.07 and 59.2% vs. 32.7%, p=0.007, respectively). Higher levels of Log (triglyceride / high density lipoprotein cholesterol), lipid accumulation product (both p <0.0001), fasting insulin and C–peptide levels (p <0.003), glycaemia in all points of oral glucose tolerance test (p<0.02), and HOMA index (p <0.002), but lower median values of Matsuda and deFronzo indices (p <0.005), as well as higher prevalence of liver steatosis (81% vs. 55%, p = 0.01) and gallbladder abnormalities (55.2% vs. 34.7%, p = 0.051) were observed in group 2 patients. Surgical menopause due to prior hysterovariectomy was observed in 55.2% of women in group 2 vs. 34.7% in group 1 (p = 0.018). During the period of observation, 27 new cases of diabetes were detected (23.8% in group 1 and 41.5% in group 2; cumulative proportion surviving 72.8% and 35.4%, respectively, p=0.039). Despite the long–term atorvastatin therapy at daily doses of 20–40 mg, 53 cases of hospitalizations due to acute coronary syndrome, heart failure or paroxysmal arrhythmias were documented during 50–months follow–up period, three of which were fatal (30.6% in group 1 and 65.5% in group 2), cumulative proportion surviving were 69.0% and 30.7%, respectively (p=0.0002). Furthermore, among patients with hypertriglyceridemia cardiovascular events appeared even in individuals with LDL-cholesterol levels <1.8 mmol/L. Conclusions. Patients with lower serum lipid levels were more likely to develop dilatation of cardiac chambers that explains higher prevalence of both atrial fibrillation and atrioventricular regurgitation. Hypertriglyceridemia was associated with fasting hyperinsulinemia and impaired postprandial insulin secretion, more severe hyperglycaemia, and lower tissue insulin sensitivity that explain higher risk of diabetes. In combination with qualitative lipid abnormalities (e.g., predominance of small dense LDL particles) and ectopic lipid deposition, these metabolic disorders predispose to typical comorbidity, i.e., liver steatosis, biliary sludge and increased bile lithogenicity. In women, hypertriglyceridemia often resulted from hysterovariectomy. Despite statin therapy with achievement of LDL-cholesterol levels <1.8 mmol/L, patients with hypertriglyceridemia had a higher risk of cardiovascular complications.

Keywords: serum triglycerides, coronary artery disease, diabetes, cardiovascular events

Full text: PDF (Ukr) 2.29M

References
  1. Berglund L, Brunzell JD, Goldberg AC, Goldberg IJ, Sacks F, Murad MH et al. Evaluation and treatment of hypertriglyceridemia: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2012; 97(9):2969–89. PMID: 22962670. PMCID: PMC3431581. https://doi.org/10.1210/jc.2011–3213
  2. Miller M, Stone NJ, Ballantyne C, Bittner V, Criqui MH, Ginsberg HN, et al. Triglycerides and cardiovascular disease: a scientific statement from the American Heart Association. Circulation. 2011; 123(20): 2292–333. PMID: 21502576. https://doi.org/10.1161/CIR.0b013e3182160726
  3. Sarwar N, Danesh J, Eiriksdottir G, Sigurdsson G, Wareham N. Bingham S. et al. Triglycerides and the risk of coronary heart disease 10 158 incident cases among 262 525 participants in 29 western prospective studies. Circulation. 2007; 115: 450–8. PMID: 17190864. https://doi.org/10.1161/circulationaha.106.637793
  4. Chapman MJ, Ginsberg HN, Amarenco P, Andreotti F, Borén J, Catapano AL, et al. Triglyceride–rich lipoproteins and high–density lipoprotein cholesterol in patients at high risk of cardiovascular disease: evidence and guidance for management. Eur Heart J. 2011; 32(11): 1345–61. PMID: 21531743. PMCID: PMC3105250. https://doi.org/10.1093/eurheartj/ehr112
  5. Di Angelantonio E, Sarwar N, Perry P, Kaptoge S, Ray KK, Thompson A, et al. Major lipids, apolipoproteins, and risk of vascular disease. Emerging Risk Factors Collaboration. JAMA. 2009; 302(18): 1993–2000. PMID: 19903920. PMCID: PMC3284229. https://doi.org/10.1001/jama.2009.1619
  6. Reiner Ž. Hypertriglyceridaemia and risk of coronary artery disease. Nat Rev Cardiol. 2017; 14(7): 401–11. PMid: 28300080. https://doi.org/10.1038/nrcardio.2017.31
  7. Bos G, Dekker JM, Nijpels G, de Vegt F, Diamant M, Stehouwer CD, et al. A combination of high concentrations of serum triglyceride and non–high–density–lipoprotein–cholesterol is a risk factor for cardiovascular disease in subjects with abnormal glucose metabolism – The Hoorn Study. Diabetologia. 2003; 46(7): 910–6. PMID: 12819906. https://doi.org/10.1007/s00125–003–1141–5
  8. Schulze MB, Shai I, Manson JE, Li T, Rifai N, Jiang R, et al. Joint role of non–HDL cholesterol and glycated haemoglobin in predicting future coronary heart disease events among women with type 2 diabetes. Diabetologia. 2004; 47(12): 2129–36. PMID :15662553. https://doi.org/10.1007/s00125–004–1593–2
  9. Gotto AM Jr, Whitney E, Stein EA, Shapiro DR, Clearfield M, Weis S, et al. Relation Between Baseline and On–Treatment Lipid Parameters and First Acute Major Coronary Events in the Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS). Circulation. 2000; 101: 477–84. PMID: 10662743. https://doi.org/10.1161/01.CIR.101.5.477
  10. Robins SJ, Collins D, Wittes JT, Papademetriou V, Deedwania PC, Schaefer EJ, et al. Relation of Gemfibrozil Treatment and Lipid Levels With Major Coronary Events: VA–HIT: A Randomized Controlled Trial. JAMA. 2001; 285(12): 1585591. PMID: 11268266. https://doi.org/10.1001/jama.285.12.1585
  11. Cosentino F, Grant PJ, Aboyans V, Bailey CJ, Ceriello A, Delgado V, et al. 2019 ESC Guidelines on diabetes, pre–diabetes, and cardiovascular diseases developed in collaboration with the EASD. Eur Heart J. 2019 Aug 31. pii: ehz486. PMID: 31497854. https://doi.org/10.1093/eurheartj/ehz486
  12. Fontbonne A, Eschwège E, Cambien F, Richard JL, Ducimetière P, Thibult N, et al. Hypertriglyceridaemia as a risk factor of coronary heart disease mortality in subjects with impaired glucose tolerance or diabetes. Results from the 11–year follow–up of the Paris Prospective Study. Diabetologia. 1989; 32(5): 300–4. PMID: 2666216. https://doi.org/10.1007/BF00265546
  13. Murad MH, Hazem A, Coto–Yglesias F, Dzyubak S, Gupta S, Bancos I, et al. The association of hypertriglyceridemia with cardiovascular events and pancreatitis: a systematic review and meta–analysis. BMC Endocr Disord. 2012; 12: 2. PMID: 22463676. PMCID: PMC3342117. https://doi.org/10.1186/1472–6823–12–2
  14. Puri R, Nissen SE, Shao M, Elshazly MB, Kataoka Y, Kapadia SR, et al. Non–HDL Cholesterol and Triglycerides: Implications for Coronary Atheroma Progression and Clinical Events. Arterioscler Thromb Vasc Biol. 2016; 36(11): 2220–8. PMID: 27515380. https://doi.org/org/10.1161/ATVBAHA.116.307601
  15. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta–cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985; 28(7): 412–9. PMID: 3899825. https://doi.org/10.1007/bf00280883
  16. Matsuda M, DeFronzo RA. Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp. Diabetes Care. 1999; 22(9): 1462–70. PMid: 10480510. https://doi.org/10.2337/diacare.22.9.1462
  17. Abdul–Ghani MA, Jenkinson CP, Richardson DK, Tripathy D, DeFronzo RA. Insulin secretion and action in subjects with impaired fasting glucose and impaired glucose tolerance: results from the Veterans Administration Genetic Epidemiology Study. Diabetes. 2006; 55(5): 1430–5. PMID: 16644701. https://doi.org/10.2337/db05–1200
  18. Dobiásová М, Frohlich J. The plasma parameter log (TG/HDL–C) as an atherogenic index: correlation with lipoprotein particle size and esterification rate in apoB–lipoprotein–depleted plasma (FERHDL). Clin Biochem. 2001; 34(7): 583–8. https://doi.org/10.1016/S0009–9120(01)00263–6
  19. Ioachimescu AG, Brennan DM, Hoar BM, Hoogwerf BJ The lipid accumulation product and all–cause mortality in patients at high cardiovascular risk: a PreCIS Database Study. Obesity (Silver Spring). 2010; 18(9): 1836–44. PMID: 20035284. https://doi.org/10.1038/oby.2009.453
  20. Cho ME, Craven TE, Cheung AK, Glasser SP, Rahman M, Soliman EZ et al. The association between insulin resistance and atrial fibrillation: A cross–sectional analysis from SPRINT (Systolic Blood Pressure Intervention Trial). J Clin Hypertens (Greenwich). 2017; 19(11): 1152–61. PMID: 28866864. https://doi.org/10.1111/jch.13062
  21. Suzuki S. “Cholesterol Paradox” in atrial fibrillation. Circ J. 2011; 75(12): 2749–50. PMID: 22027365. https://doi.org/10.1253/circj.cj–11–1134
  22. Korolyuk OY, Radchenko OM Hypocholesterolemia in acute coronary syndrome: prognostic value, peculiarities of disease trend, unfavorable factors (literature review and own investigations). Medychna gidrologiya ta reabilitatsiya. 2009; 7(2): 106–16.
  23. Velagaleti RS, Massaro J, Vasan RS, Robins SJ, Kannel WB, Levy D. Relations of lipid concentrations to heart failure incidence: the Framingham Heart Study. Circulation. 2009; 120(23): 2345–51. PMid: 19933936. PMCid: PMC3600834. https://doi.org/10.1161/CIRCULATIONAHA.109.830984
  24. Unger RH. Weapons of lean body mass destruction: the role of ectopic lipids in the metabolic syndrome. Endocrinology. 2003; 144(12): 5159–65. PMid: 12960011. https://doi.org/10.1210/en.2003–0870
  25. Goonasekara CL, Balse E, Hatem S, Steele DF, Fedida D. Cholesterol and cardiac arrhythmias. Expert Rev Cardiovasc Ther. 2010; 8(7):965–79. PMID: 20602558. https://doi.org/10.1586/erc.10.79.
  26. Abi–Char J, Maguy A, Coulombe A, Balse E, Ratajczak P, Samuel JL, et al. Membrane cholesterol modulates Kv1.5 potassium channel distribution and function in rat cardiomyocytes. J Physiol. 2007; 582(Pt 3): 1205–17. PMID: 17525113. PMCID: PMC2075263. https://doi.org/10.1113/jphysiol.2007.134809
  27. Liu Q, Bengmark S, Qu S. The role of hepatic fat accumulation in pathogenesis of non–alcoholic fatty liver disease (NAFLD). Lipids Health Dis. 2010; 9: 42. PMID: 20426802. PMCID: PMC2873482. https://doi.org/10.1186/1476–511X–9–42
  28. Takeshita A, Yamamoto K, Fujita A, Hanafusa T, Yasuda E, Shibayama Y. Focal hepatic steatosis surrounding a metastatic insulinoma. Pathol Int. 2008; 58(1): 59–63. PMID: 18067643. https://doi.org/10.1111/j.1440–1827.2007.02190.x
  29. Biddinger SB, Hernandez–Ono A, Rask–Madsen C, Haas JT, Alemán JO, Suzuki R, et al. Hepatic insulin resistance is sufficient to produce dyslipidemia and susceptibility to atherosclerosis. Cell Metab. 2008; 7(2): 125–34. PMID: 18249172. PMCID: PMC4251554. https://doi.org/10.1016/j.cmet.2007.11.013
  30. Lee J, Lee YA, Kim JH, Lee SY, Shin CH, Yang SW. Discrepancies between glycosylated hemoglobin and fasting plasma glucose for diagnosing impaired fasting glucose and diabetes mellitus in Korean youth and young adults. Diabetes Metab J. 2019; 43(2): 174–82. PMID: 30398041. PMCID: PMC6470094. https://doi.org/10.4093/dmj.2018.0046
  31. Sequeira IR, Poppitt SD. HbA1c as a marker of prediabetes: A reliable screening tool or not? Insights Nutr Metabol. 2017; 1(1): 11–20.
  32. Smelt AH. Triglycerides and gallstone formation. Clin Chim Acta. 2010 11; 411(21–22): 1625–31. PMID: 20699090. https://doi.org/10.1016/j.cca.2010.08.003
  33. Weerakoon HT, Ranasinghe S, Navaratne A, Sivakanesan R, Galketiya KB, Rosairo S. Serum lipid concentrations in patients with cholesterol and pigment gallstones. BMC Res Notes. 2014 19; 7: 548. PMID: 25135323. PMCID: PMC4143546. https://doi.org/10.1186/1756–0500–7–548
  34. Jonkers IJ, Smelt AH, Ledeboer M, Hollum ME, Biemond I, Kuipers F et al. Gall bladder dysmotility: a risk factor for gall stone formation in hypertriglyceridaemia and reversal on triglyceride lowering therapy by bezafibrate and fish oil. Gut. 2003; 52(1): 109–15. PMID: 12477770. PMCID: PMC1773519. https://doi.org/10.1136/gut.52.1.109
  35. Wang HH, Portincasa P, Liu M, Tso P, Samuelson LC, Wang DQ. Effect of gallbladder hypomotility on cholesterol crystallization and growth in CCK–deficient mice. Biochim Biophys Acta. 2010; 1801(2): 138–46. PMID: 19836465. PMCID: PMC2830894. https://doi.org/10.1016/j.bbalip.2009.10.003
  36. Li PC, Tsai IJ, Hsu CY, Wang JH, Lin SZ, Ding DC, et al. Risk of Hyperlipidemia in women with hysterectomy – a retrospective cohort study in Taiwan. Sci Rep. 2018; 8(1): 12956. PMID: 30154502 PMCID: PMC6113310. https://doi.org/10.1038/s41598–018–31347–z
  37. Miller M, Cannon CP, Murphy SA, Qin J, Ray KK, Braunwald E et al. Impact of triglyceride levels beyond low–density lipoprotein cholesterol after acute coronary syndrome in the PROVE IT–TIMI 22 trial. J Am Coll Cardiol. 2008; 51(7): 724–30. PMID: 18279736. https://doi.org/10.1016/j.jacc.2007.10.038
  38. Schwartz GG, Abt M, Bao W, DeMicco D, Kallend D, Miller M, et al. Fasting triglycerides predict recurrent ischemic events in patients with acute coronary syndrome treated with statins. J Am Coll Cardiol. 2015; 65(21): 2267–75. PMID: 26022813. https://doi.org/10.1016/j.jacc.2015.03.544