Elevated plasma triglyceride concentration and risk of adverse clinical outcomes in 1.5 million people: a CALIBER linked electronic health record study

Riyaz S. Patel; Laura Pasea; Handrean Soran; Paul Downie; Richard Jones; Aroon D. Hingorani; Dermot Neely; Spiros Denaxas; Harry Hemingway

doi:10.1186/s12933-022-01525-5

journal article Open Access Jun 09, 2022

Elevated plasma triglyceride concentration and risk of adverse clinical outcomes in 1.5 million people: a CALIBER linked electronic health record study

Riyaz S. Patel Laura Pasea Handrean Soran Paul Downie Richard Jones Aroon D. Hingorani

Dermot Neely Spiros Denaxas

Harry Hemingway

Cardiovascular Diabetology Vol. 21 No. 1 · Springer Science and Business Media LLC

View at Publisher Save 10.1186/s12933-022-01525-5

Abstract

Abstract
Background
Assessing the spectrum of disease risk associated with hypertriglyceridemia is needed to inform potential benefits from emerging triglyceride lowering treatments. We sought to examine the associations between a full range of plasma triglyceride concentration with five clinical outcomes.

Methods
We used linked data from primary and secondary care for 15 M people, to explore the association between triglyceride concentration and risk of acute pancreatitis, chronic pancreatitis, new onset diabetes, myocardial infarction and all-cause mortality, over a median of 6–7 years follow up.

Results
Triglyceride concentration was available for 1,530,411 individuals (mean age 56·6 ± 15·6 years, 51·4% female), with a median of 1·3 mmol/L (IQR: 0.9.to 1.9). Severe hypertriglyceridemia, defined as > 10 mmol/L, was identified in 3289 (0·21%) individuals including 620 with > 20 mmol/L. In multivariable analyses, a triglyceride concentration > 20 mmol/L was associated with very high risk for acute pancreatitis (Hazard ratio (HR) 13·55 (95% CI 9·15–20·06)); chronic pancreatitis (HR 25·19 (14·91–42·55)); and high risk for diabetes (HR 5·28 (4·51–6·18)) and all-cause mortality (HR 3·62 (2·82–4·65)) when compared to the reference category of ≤ 1·7 mmol/L. An association with myocardial infarction, however, was only observed for more moderate hypertriglyceridaemia between 1.7 and 10 mmol/L. We found a risk interaction with age, with higher risks for all outcomes including mortality among those ≤ 40 years compared to > 40 years.

Conclusions
We highlight an exponential association between severe hypertriglyceridaemia and risk of incident acute and chronic pancreatitis, new diabetes, and mortality, especially at younger ages, but not for myocardial infarction for which only moderate hypertriglyceridemia conferred risk.

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References

37

[1]

Hansen SEJ, Madsen CM, Varbo A, Nordestgaard BG. Body mass index, triglycerides, and risk of acute pancreatitis: a population-based study of 118,000 individuals. J Clin Endocrinol Metab. 2020;105(1):163–74. 10.1210/clinem/dgz059

[2]

Volanesorsen and Triglyceride Levels in Familial Chylomicronemia Syndrome

Joseph L. Witztum, Daniel Gaudet, Steven D. Freedman et al.

New England Journal of Medicine 2019 10.1056/nejmoa1715944

[3]

Holmes MV, Asselbergs FW, Palmer TM, et al. Mendelian randomization of blood lipids for coronary heart disease. Eur Heart J 2015; 36(9): 539–50. 10.1093/eurheartj/eht571

[4]

Simha V. Management of hypertriglyceridemia. BMJ 2020; 371: m3109. 10.1136/bmj.m3109

[5]

Berglund L, Brunzell JD, Goldberg AC, et al. Evaluation and treatment of hypertriglyceridemia: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2012; 97(9): 2969–89. 10.1210/jc.2011-3213

[6]

2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk

François Mach, Colin Baigent, Alberico L. Catapano et al.

European Heart Journal 2020 10.1093/eurheartj/ehz455

[7]

Triglyceride-Rich Lipoproteins and Atherosclerotic Cardiovascular Disease

Børge G. Nordestgaard

Circulation Research 2016 10.1161/circresaha.115.306249

[8]

Boren J, Williams KJ. The central role of arterial retention of cholesterol-rich apolipoprotein-B-containing lipoproteins in the pathogenesis of atherosclerosis: a triumph of simplicity. Curr Opin Lipidol 2016; 27(5): 473–83. 10.1097/mol.0000000000000330

[9]

Sandhu S, Al-Sarraf A, Taraboanta C, Frohlich J, Francis GA. Incidence of pancreatitis, secondary causes, and treatment of patients referred to a specialty lipid clinic with severe hypertriglyceridemia: a retrospective cohort study. Lipids Health Dis 2011; 10: 157. 10.1186/1476-511x-10-157

[10]

Toth PP, Grabner M, Ramey N, Higuchi K. Clinical and economic outcomes in a real-world population of patients with elevated triglyceride levels. Atherosclerosis 2014; 237(2): 790–7. 10.1016/j.atherosclerosis.2014.09.029

[11]

Zafrir B, Jubran A, Hijazi R, Shapira C. Clinical features and outcomes of severe, very severe, and extreme hypertriglyceridemia in a regional health service. J Clin Lipidol 2018; 12(4): 928–36. 10.1016/j.jacl.2018.03.086

[12]

Herrett E, Shah AD, Boggon R, et al. Completeness and diagnostic validity of recording acute myocardial infarction events in primary care, hospital care, disease registry, and national mortality records: cohort study. BMJ 2013; 346: f2350. 10.1136/bmj.f2350

[13]

Denaxas S, Gonzalez-Izquierdo A, Direk K, et al. UK phenomics platform for developing and validating electronic health record phenotypes: CALIBER. J Am Med Inform Assoc 2019; 26(12): 1545–59. 10.1093/jamia/ocz105

[14]

Estimation of the Concentration of Low-Density Lipoprotein Cholesterol in Plasma, Without Use of the Preparative Ultracentrifuge

William T Friedewald, Robert I Levy, Donald S Fredrickson

Clinical Chemistry 1972 10.1093/clinchem/18.6.499

[15]

Nonfasting Mild-to-Moderate Hypertriglyceridemia and Risk of Acute Pancreatitis

Simon B. Pedersen, Anne Langsted, Børge G. Nordestgaard

JAMA Internal Medicine 2016 10.1001/jamainternmed.2016.6875

[16]

Nordestgaard BG, Benn M, Schnohr P, Tybjaerg-Hansen A. Nonfasting triglycerides and risk of myocardial infarction, ischemic heart disease, and death in men and women. JAMA 2007; 298(3): 299–308. 10.1001/jama.298.3.299

[17]

Fasting Compared With Nonfasting Triglycerides and Risk of Cardiovascular Events in Women

Sandeep Bansal, Julie E. Buring, Nader Rifai et al.

JAMA 2007 10.1001/jama.298.3.309

[18]

Major Lipids, Apolipoproteins, and Risk of Vascular Disease

The Emerging Risk Factors Collaboration*

JAMA 2009 10.1001/jama.2009.1619

[19]

Nordestgaard BG, Varbo A. Triglycerides and cardiovascular disease. Lancet 2014; 384(9943): 626–35. 10.1016/s0140-6736(14)61177-6

[20]

Triglycerides and the Risk of Coronary Heart Disease

Nadeem Sarwar, John Danesh, Gudny Eiriksdottir et al.

Circulation 2007 10.1161/circulationaha.106.637793

[21]

Christian JB, Arondekar B, Buysman EK, Johnson SL, Seeger JD, Jacobson TA. Clinical and economic benefits observed when follow-up triglyceride levels are less than 500 mg/dL in patients with severe hypertriglyceridemia. J Clin Lipidol 2012; 6(5): 450–61. 10.1016/j.jacl.2012.08.007

[22]

Chait A, Eckel RH. The chylomicronemia syndrome is most often multifactorial: a narrative review of causes and treatment. Ann Intern Med. 2019;170(9):626–34. 10.7326/m19-0203

[23]

Chylomicronaemia—current diagnosis and future therapies

Amanda J. Brahm, Robert A. Hegele

Nature Reviews Endocrinology 2015 10.1038/nrendo.2015.26

[24]

Veenstra J, Ockhuizen T, van de Pol H, Wedel M, Schaafsma G. Effects of a moderate dose of alcohol on blood lipids and lipoproteins postprandially and in the fasting state. Alcohol Alcohol 1990; 25(4): 371–7.

[25]

Vipperla K, Somerville C, Furlan A, et al. Clinical profile and natural course in a large cohort of patients with hypertriglyceridemia and pancreatitis. J Clin Gastroenterol. 2017;51(1):77–85. 10.1097/mcg.0000000000000579

[26]

Patients with type 2 diabetes mellitus have higher risk for acute pancreatitis compared with those without diabetes

C. J. Girman, T. D. Kou, B. Cai et al.

Diabetes, Obesity and Metabolism 2010 10.1111/j.1463-1326.2010.01231.x

[27]

Grundy SM. Hypertriglyceridemia, insulin resistance, and the metabolic syndrome. Am J Cardiol 1999; 83(9B): 25F-9F.

[28]

Klempfner R, Erez A, Sagit BZ, et al. Elevated triglyceride level is independently associated with increased all-cause mortality in patients with established coronary heart disease: twenty-two-year follow-up of the bezafibrate infarction prevention study and registry. Circ Cardiovasc Qual Outcomes. 2016;9(2):100–8. 10.1161/circoutcomes.115.002104

[29]

Nordestgaard BG, Zilversmit DB. Large lipoproteins are excluded from the arterial wall in diabetic cholesterol-fed rabbits. J Lipid Res 1988; 29(11): 1491–500. 10.1016/s0022-2275(20)38428-5

[30]

Luijten J, van Greevenbroek MMJ, Schaper NC, et al. Incidence of cardiovascular disease in familial combined hyperlipidemia: a 15-year follow-up study. Atherosclerosis. 2019;280:1–6. 10.1016/j.atherosclerosis.2018.11.013

[31]

Sniderman AD, Couture P, Martin SS, et al. Hypertriglyceridemia and cardiovascular risk: a cautionary note about metabolic confounding. J Lipid Res 2018; 59(7): 1266–75. 10.1194/jlr.r082271

[32]

Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90 056 participants in 14 randomised trials of statins

The Lancet 2005 10.1016/s0140-6736(05)67394-1

[33]

Preiss D, Tikkanen MJ, Welsh P, et al. Lipid-modifying therapies and risk of pancreatitis: a meta-analysis. JAMA 2012; 308(8): 804–11. 10.1001/jama.2012.8439

[34]

Rashid N, Sharma PP, Scott RD, Lin KJ, Toth PP. Severe hypertriglyceridemia and factors associated with acute pancreatitis in an integrated health care system. J Clin Lipidol 2016; 10(4): 880–90. 10.1016/j.jacl.2016.02.019

[35]

Gaudet D, Alexander VJ, Baker BF, et al. Antisense inhibition of apolipoprotein C-III in patients with hypertriglyceridemia. N Engl J Med. 2015;373(5):438–47. 10.1056/nejmoa1400283

[36]

Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation 2019; 139(25): e1082-e143. 10.1161/cir.0000000000000698

[37]

Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia

Deepak L. Bhatt, P. Gabriel Steg, Michael Miller et al.

New England Journal of Medicine 2019 10.1056/nejmoa1812792

Metrics

36

Citations

37

References

Details

Published: Jun 09, 2022
Vol/Issue: 21(1)
License: View

Authors

Institute of Health Informatics, University College London, London, UK; Health Data Research UK, University College London, London, UK

Department of Clinical Biochemistry, Bristol Royal Infirmary, Bristol, UK

Institute of Health Informatics, University College London, London, UK; British Heart Foundation Data Science Centre, Health Data Research Centre UK, London, United Kingdom

H

Harry Hemingway

The Farr Institute, University College London, UK

Funding

British Heart Foundation Award: FS/14/76/30933

Akcea Therapeutics

Cite This Article

Riyaz S. Patel, Laura Pasea, Handrean Soran, et al. (2022). Elevated plasma triglyceride concentration and risk of adverse clinical outcomes in 1.5 million people: a CALIBER linked electronic health record study. Cardiovascular Diabetology, 21(1). https://doi.org/10.1186/s12933-022-01525-5

Elevated plasma triglyceride concentration and risk of adverse clinical outcomes in 1.5 million people: a CALIBER linked electronic health record study

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