open access

Vol 26, No 5 (2019)
Original articles — Clinical cardiology
Published online: 2018-09-13
Get Citation

Lipoprotein(a) screening in young and middle-aged patients presenting with acute coronary syndrome

Ayman Jubran, Anna Zetser, Barak Zafrir
DOI: 10.5603/CJ.a2018.0106
·
Pubmed: 30234895
·
Cardiol J 2019;26(5):511-518.

open access

Vol 26, No 5 (2019)
Original articles — Clinical cardiology
Published online: 2018-09-13

Abstract

Background: Elevated lipoprotein(a) [Lp(a)] is an independent risk factor for coronary artery disease (CAD). However, its role in real-world practice and implications for clinical care remains limited. Under investigation herein, are the clinical characteristics associated with increased Lp(a) levels in patients presenting with acute coronary syndrome (ACS).


Methods: Lp(a) was measured at admission in patients ≤ 65 years of age presenting with ACS in a single center. Logistic regression model was used to determine the independent association of clinical characteristics with elevated Lp(a).


Results: A total of 134 patients were screened for Lp(a); 83% males, mean age 52 ± 8 years. Median Lp(a) level was 46 nmol/L (interquartile range [IQR] 13–91). Elevated Lp(a) > 72 nmol/L (30 mg/dL) was documented in 32% and associated with younger age at CAD diagnosis. In a multiple logistic regression model, premature CAD (odds ratio [OR] 3.85, 95% confidence interval [CI] 1.48–10.07, p = 0.06), previous revascularization (OR 2.56, 95% CI 1.17–5.59, p = 0.019) and probable/definite familial hypercholesterolemia (FH) (OR 3.18, 95% CI 1.10–9.21, p = 0.033), were independently associated with elevated Lp(a). In contrast, Lp(a) levels were not associated with other traditional cardiovascular risk factors, previous statin treatment, C-reactive protein level or ACS type.


Conclusions: In young and middle-aged patients presenting with ACS, premature CAD, previous revascularization and FH were independently associated with elevated Lp(a), indicating progressive CAD and higher cardiovascular risk. These results, are in accordance with guideline based recommendations for Lp(a) screening, and may be of importance in addressing residual cardiovascular risk in young ACS patients, in light of the novel emerging therapies targeting Lp(a).

Abstract

Background: Elevated lipoprotein(a) [Lp(a)] is an independent risk factor for coronary artery disease (CAD). However, its role in real-world practice and implications for clinical care remains limited. Under investigation herein, are the clinical characteristics associated with increased Lp(a) levels in patients presenting with acute coronary syndrome (ACS).


Methods: Lp(a) was measured at admission in patients ≤ 65 years of age presenting with ACS in a single center. Logistic regression model was used to determine the independent association of clinical characteristics with elevated Lp(a).


Results: A total of 134 patients were screened for Lp(a); 83% males, mean age 52 ± 8 years. Median Lp(a) level was 46 nmol/L (interquartile range [IQR] 13–91). Elevated Lp(a) > 72 nmol/L (30 mg/dL) was documented in 32% and associated with younger age at CAD diagnosis. In a multiple logistic regression model, premature CAD (odds ratio [OR] 3.85, 95% confidence interval [CI] 1.48–10.07, p = 0.06), previous revascularization (OR 2.56, 95% CI 1.17–5.59, p = 0.019) and probable/definite familial hypercholesterolemia (FH) (OR 3.18, 95% CI 1.10–9.21, p = 0.033), were independently associated with elevated Lp(a). In contrast, Lp(a) levels were not associated with other traditional cardiovascular risk factors, previous statin treatment, C-reactive protein level or ACS type.


Conclusions: In young and middle-aged patients presenting with ACS, premature CAD, previous revascularization and FH were independently associated with elevated Lp(a), indicating progressive CAD and higher cardiovascular risk. These results, are in accordance with guideline based recommendations for Lp(a) screening, and may be of importance in addressing residual cardiovascular risk in young ACS patients, in light of the novel emerging therapies targeting Lp(a).

Get Citation

Keywords

lipoprotein(a); acute coronary syndrome; coronary artery disease; familial hypercholesterolemia

About this article
Title

Lipoprotein(a) screening in young and middle-aged patients presenting with acute coronary syndrome

Journal

Cardiology Journal

Issue

Vol 26, No 5 (2019)

Pages

511-518

Published online

2018-09-13

DOI

10.5603/CJ.a2018.0106

Pubmed

30234895

Bibliographic record

Cardiol J 2019;26(5):511-518.

Keywords

lipoprotein(a)
acute coronary syndrome
coronary artery disease
familial hypercholesterolemia

Authors

Ayman Jubran
Anna Zetser
Barak Zafrir

References (41)
  1. Nordestgaard BG, Langsted A. Lipoprotein (a) as a cause of cardiovascular disease: insights from epidemiology, genetics, and biology. J Lipid Res. 2016; 57(11): 1953–1975.
  2. Tsimikas S. A test in context: lipoprotein(a): diagnosis, prognosis, controversies, and emerging therapies. J Am Coll Cardiol. 2017; 69(6): 692–711.
  3. Kamstrup PR, Benn M, Tybjaerg-Hansen A, et al. Extreme lipoprotein(a) levels and risk of myocardial infarction in the general population: the Copenhagen City Heart Study. Circulation. 2008; 117(2): 176–184.
  4. Erqou S, Kaptoge S, Perry PL, et al. Lipoprotein(a) concentration and the risk of coronary heart disease, stroke, and nonvascular mortality. JAMA. 2009; 302(4): 412–423.
  5. Kamstrup PR, Tybjærg-Hansen A, Nordestgaard BG. Extreme lipoprotein(a) levels and improved cardiovascular risk prediction. J Am Coll Cardiol. 2013; 61(11): 1146–1156.
  6. Nestel PJ, Barnes EH, Tonkin AM, et al. Plasma lipoprotein(a) concentration predicts future coronary and cardiovascular events in patients with stable coronary heart disease. Arterioscler Thromb Vasc Biol. 2013; 33(12): 2902–2908.
  7. Willeit P, Kiechl S, Kronenberg F, et al. Discrimination and net reclassification of cardiovascular risk with lipoprotein(a): prospective 15-year outcomes in the Bruneck Study. J Am Coll Cardiol. 2014; 64(9): 851–860.
  8. O'Donoghue ML, Morrow DA, Tsimikas S, et al. Lipoprotein(a) for risk assessment in patients with established coronary artery disease. J Am Coll Cardiol. 2014; 63(6): 520–527.
  9. Clarke R, Peden JF, Hopewell JC, et al. PROCARDIS Consortium. Genetic variants associated with Lp(a) lipoprotein level and coronary disease. N Engl J Med. 2009; 361(26): 2518–2528.
  10. Kamstrup PR, Tybjaerg-Hansen A, Steffensen R, et al. Genetically elevated lipoprotein(a) and increased risk of myocardial infarction. JAMA. 2009; 301(22): 2331–2339.
  11. Waldeyer C, Makarova N, Zeller T, et al. Lipoprotein(a) and the risk of cardiovascular disease in the European population: results from the BiomarCaRE consortium. Eur Heart J. 2017; 38(32): 2490–2498.
  12. Marcovina SM, Albers JJ. Lipoprotein (a) measurements for clinical application. J Lipid Res. 2016; 57(4): 526–537.
  13. Tsimikas S, Fazio S, Ferdinand KC, et al. NHLBI Working Group Recommendations to Reduce Lipoprotein(a)-Mediated Risk of Cardiovascular Disease and Aortic Stenosis. J Am Coll Cardiol. 2018; 71(2): 177–192.
  14. Catapano AL, Graham I, De Backer G, et al. 2016 ESC/EAS guidelines for the management of dyslipidaemias. Eur Heart J. 2016; 37(39): 2999–3058.
  15. Viney NJ, van Capelleveen JC, Geary RS, et al. Antisense oligonucleotides targeting apolipoprotein(a) in people with raised lipoprotein(a): two randomised, double-blind, placebo-controlled, dose-ranging trials. Lancet. 2016; 388(10057): 2239–2253.
  16. Slunga L, Johnson O, Dahlén GH, et al. Lipoprotein(a) and acute-phase proteins in acute myocardial infarction. Scand J Clin Lab Invest. 1992; 52(2): 95–101.
  17. Min WK, Lee JO, Huh JW. Relation between lipoprotein(a) concentrations in patients with acute-phase response and risk analysis for coronary heart disease. Clin Chem. 1997; 43(10): 1891–1895.
  18. Nordestgaard BG, Chapman MJ, Ray K, et al. Lipoprotein(a) as a cardiovascular risk factor: current status. Eur Heart J. 2010; 31(23): 2844–2853.
  19. Civeira F. International Panel on Management of Familial Hypercholesterolemia. Guidelines for the diagnosis and management of heterozygous familial hypercholesterolemia. Atherosclerosis. 2004; 173(1): 55–68.
  20. Varvel S, McConnell JP, Tsimikas S. Prevalence of elevated lp(a) mass levels and patient thresholds in 532 359 patients in the united states. Arterioscler Thromb Vasc Biol. 2016; 36(11): 2239–2245.
  21. Khera AV, Everett BM, Caulfield MP, et al. Lipoprotein(a) concentrations, rosuvastatin therapy, and residual vascular risk: an analysis from the JUPITER Trial (Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin). Circulation. 2014; 129(6): 635–642.
  22. Stubbs P, Seed M, Lane D, et al. Lipoprotein(a) as a risk predictor for cardiac mortality in patients with acute coronary syndromes. Eur Heart J. 1998; 19(9): 1355–1364.
  23. Rallidis LS, Pavlakis G, Foscolou A, et al. High levels of lipoprotein (a) and premature acute coronary syndrome. Atherosclerosis. 2018; 269: 29–34.
  24. Zhou J, Cui X, Jin X, et al. Association between Lipoprotein (a) level on admission and the incidence of subsequent cardiovascular events in patients with acute coronary syndrome. Int J Cardiol. 2012; 158(3): 464–466.
  25. Rallidis LS, Pavlakis G, Foscolou A, et al. High levels of lipoprotein (a) and premature acute coronary syndrome. Atherosclerosis. 2018; 269: 29–34.
  26. Schwartz GG, Ballantyne CM, Barter PJ, et al. Association of Lipoprotein(a) With Risk of Recurrent Ischemic Events Following Acute Coronary Syndrome: Analysis of the dal-Outcomes Randomized Clinical Trial. JAMA Cardiol. 2018; 3(2): 164–168.
  27. Zewinger S, Kleber ME, Tragante V, et al. Relations between lipoprotein(a) concentrations, LPA genetic variants, and the risk of mortality in patients with established coronary heart disease: a molecular and genetic association study. Lancet Diabetes Endocrinol. 2017; 5(7): 534–543.
  28. Puri R, Ballantyne CM, Hoogeveen RC, et al. Lipoprotein(a) and coronary atheroma progression rates during long-term high-intensity statin therapy: Insights from SATURN. Atherosclerosis. 2017; 263: 137–144.
  29. Albers JJ, Slee A, O'Brien KD, et al. Relationship of apolipoproteins A-1 and B, and lipoprotein(a) to cardiovascular outcomes: the AIM-HIGH trial (Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglyceride and Impact on Global Health Outcomes). J Am Coll Cardiol. 2013; 62(17): 1575–1579.
  30. Suwa S, Ogita M, Miyauchi K, et al. Impact of Lipoprotein (a) on Long-Term Outcomes in Patients with Coronary Artery Disease Treated with Statin After a First Percutaneous Coronary Intervention. J Atheroscler Thrombis. 2017; 24(11): 1125–1131.
  31. Nordestgaard BG, Chapman MJ, Humphries SE, et al. Familial hypercholesterolaemia is underdiagnosed and undertreated in the general population: guidance for clinicians to prevent coronary heart disease: consensus statement of the European Atherosclerosis Society. Eur Heart J. 2013; 34(45): 3478–90a.
  32. Jansen ACM, van Aalst-Cohen ES, Tanck MW, et al. The contribution of classical risk factors to cardiovascular disease in familial hypercholesterolaemia: data in 2400 patients. J Intern Med. 2004; 256(6): 482–490.
  33. Alonso R, Andres E, Mata N, et al. Lipoprotein(a) levels in familial hypercholesterolemia: an important predictor of cardiovascular disease independent of the type of LDL receptor mutation. J Am Coll Cardiol. 2014; 63(19): 1982–1989.
  34. Langsted A, Kamstrup PR, Benn M, et al. High lipoprotein(a) as a possible cause of clinical familial hypercholesterolaemia: a prospective cohort study. Lancet Diabetes Endocrinol. 2016; 4(7): 577–587.
  35. Ellis KL, Pang J, Chieng D, et al. Elevated lipoprotein(a) and familial hypercholesterolemia in the coronary care unit: Between Scylla and Charybdis. Clin Cardiol. 2018; 41(3): 378–384.
  36. Zafrir B, Shapira C, Lavie G, et al. Identification and characterization of severe familial hypercholesterolemia in patients presenting for cardiac catheterization. J Clin Lipidol. 2016; 10(6): 1338–1343.
  37. Maeda S, Abe A, Seishima M, et al. Transient changes of serum lipoprotein(a) as an acute phase protein. Atherosclerosis. 1989; 78(2-3): 145–150.
  38. Dursunoğlu D, Evrengül H, Polat B, et al. Lp(a) lipoprotein and lipids in patients with rheumatoid arthritis: serum levels and relationship to inflammation. Rheumatol Int. 2005; 25(4): 241–245.
  39. Wang J, Hu B, Kong L, et al. Native, oxidized lipoprotein(a) and lipoprotein(a) immune complex in patients with active and inactive rheumatoid arthritis: plasma concentrations and relationship to inflammation. Clin Chim Acta. 2008; 390(1-2): 67–71.
  40. Kargman DE, Tuck C, Berglund L, et al. Lipid and lipoprotein levels remain stable in acute ischemic stroke: the Northern Manhattan Stroke Study. Atherosclerosis. 1998; 139(2): 391–399.
  41. Langsted A, Kamstrup PR, Nordestgaard BG. Lipoprotein(a): fasting and nonfasting levels, inflammation, and cardiovascular risk. Atherosclerosis. 2014; 234(1): 95–101.

Important: This website uses cookies. More >>

The cookies allow us to identify your computer and find out details about your last visit. They remembering whether you've visited the site before, so that you remain logged in - or to help us work out how many new website visitors we get each month. Most internet browsers accept cookies automatically, but you can change the settings of your browser to erase cookies or prevent automatic acceptance if you prefer.

By "Via Medica sp. z o.o." sp.k., ul. Świętokrzyska 73, 80–180 Gdańsk, Poland
tel.:+48 58 320 94 94, fax:+48 58 320 94 60, e-mail: viamedica@viamedica.pl