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Lipoprotein (a), hypertension, and cardiovascular outcomes: a prospective study of patients with stable coronary artery disease

Hypertension Research volume 44, pages 1158–1167 (2021)Cite this article

Abstract

Although emerging data suggest that circulating lipoprotein (a) [Lp (a)] could predict cardiovascular events (CVEs) in patients with cardiovascular disease, no study is currently available regarding the prognostic linkage of Lp (a) and hypertension in patients with coronary artery disease (CAD). This study sought to evaluate the association of Lp (a), hypertension and cardiovascular outcomes in patients with stable CAD. A total of 8668 patients with stable CAD were consecutively enrolled. Baseline Lp (a) concentrations were measured. All subjects were categorized according to Lp (a) levels of <10 (low), 10–30 (medium) and ≥30 mg/dL (high) and were further stratified by hypertension status. They were regularly followed-up for the occurrence of cardiovascular death, nonfatal myocardial infarction, and stroke. Over an average of 54.81 ± 18.60 months of follow-up, 584 (6.7%) CVEs occurred. Kaplan–Meier and multivariate Cox regression analyses showed that elevated Lp (a) levels had a significant association with CVEs in hypertensive patients, regardless of the control status of blood pressure, but not in normotensive subjects. Moreover, when analyzed by subgroups according to both Lp (a) category and hypertension status, the risk of CVEs was only significantly elevated in the high Lp (a) plus hypertension group compared with the reference group with low Lp (a) levels and normotension (hazard ratio: 1.80, 95% confidence interval: 1.11–2.91). Elevated Lp (a) was associated with an increased risk of CVEs in stable CAD patients with hypertension. Moreover, the coexistence of high Lp (a) concentrations and hypertension greatly worsened the clinical prognosis in patients with CAD, which may suggest a prognostic correlation between Lp (a) and hypertension.

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References

  1. Liu HH, Cao YX, Jin JL, Zhang HW, Hua Q, Li YF, et al. Predicting cardiovascular outcomes by baseline lipoprotein(a) concentrations: a large cohort and long-term follow-up study on real-world patients receiving percutaneous coronary intervention. J Am Heart Assoc. 2020;9:e014581.

    PubMed  PubMed Central  Google Scholar 

  2. Sechi LA, Catena C, Casaccio D, Zingaro L. Lipoprotein (a), haemostatic variables and cardiovascular damage in hypertensive patients. J Hypertens. 2000;18:709–16.

    Article  CAS  Google Scholar 

  3. Kamstrup PR, Tybjaerg-Hansen A, Steffensen R, Nordestgaard BG. Genetically elevated lipoprotein(a) and increased risk of myocardial infarction. JAMA. 2009;301:2331–9.

    Article  CAS  Google Scholar 

  4. Suk Danik J, Rifai N, Buring JE, Ridker PM. Lipoprotein(a), measured with an assay independent of apolipoprotein(a) isoform size, and risk of future cardiovascular events among initially healthy women. JAMA. 2006;296:1363–70.

    Article  CAS  Google Scholar 

  5. Nestel PJ, Barnes EH, Tonkin AM, Simes J, Fournier M, White HD, et al. Plasma lipoprotein(a) concentration predicts future coronary and cardiovascular events in patients with stable coronary heart disease. Arterioscler Thromb Vasc Biol. 2013;33:2902–8.

    Article  CAS  Google Scholar 

  6. Tsimikas S. A test in context: lipoprotein(a): diagnosis, prognosis, controversies, and emerging therapies. J Am Coll Cardiol. 2017;69:692–711.

    Article  CAS  Google Scholar 

  7. O’Donoghue ML, Morrow DA, Tsimikas S, Sloan S, Ren AF, Hoffman EB, et al. Lipoprotein(a) for risk assessment in patients with established coronary artery disease. J Am Coll Cardiol. 2014;63:520–7.

    Article  Google Scholar 

  8. Suk Danik J, Rifai N, Buring JE, Ridker PM. Lipoprotein(a), hormone replacement therapy, and risk of future cardiovascular events. J Am Coll Cardiol. 2008;52:124–31.

    Article  CAS  Google Scholar 

  9. Gragnano F, Fimiani F, Di Maio M, Cesaro A, Limongelli G, Cattano D, et al. Impact of lipoprotein(a) levels on recurrent cardiovascular events in patients with premature coronary artery disease. Intern Emerg Med. 2019;14:621–5.

    Article  Google Scholar 

  10. Jin JL, Cao YX, Zhang HW, Sun D, Hua Q, Li YF, et al. Lipoprotein(a) and cardiovascular outcomes in coronary artery disease patients with prediabetes and diabetes. Diabetes Care. 2019;42:1312–18.

  11. Li S, Wu NQ, Zhu CG, Zhang Y, Guo YL, Gao Y, et al. Significance of lipoprotein(a) levels in familial hypercholesterolemia and coronary artery disease. Atherosclerosis. 2017;260:67–74.

    Article  CAS  Google Scholar 

  12. Zhou J, Cui X, Jin X, Zhou J, Fu M, Zhong C, 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;158:464–6.

    Article  Google Scholar 

  13. Catena C, Novello M, Lapenna R, Baroselli S, Colussi G, Nadalini E, et al. New risk factors for atherosclerosis in hypertension: focus on the prothrombotic state and lipoprotein(a). J Hypertens. 2005;23:1617–31.

    Article  CAS  Google Scholar 

  14. Liu HH, Cao YX, Li S, Guo YL, Zhu CG, Wu NQ, et al. Impacts of prediabetes mellitus alone or plus hypertension on the coronary severity and cardiovascular outcomes. Hypertension. 2018;71:1039–46.

    Article  CAS  Google Scholar 

  15. Williams B, Mancia G, Spiering W, Agabiti Rosei E, Azizi M, Burnier M, et al. 2018 ESC/ESH Guidelines for the management of arterial hypertension. European heart journal. 2018;39:3021–3104.

  16. Whelton PK, Carey RM, Aronow WS, Casey DE, Jr., Collins KJ, Dennison Himmelfarb C, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension. 2018;71:1269–1324.

  17. Bennet A, Di Angelantonio E, Erqou S, Eiriksdottir G, Sigurdsson G, Woodward M, et al. Lipoprotein(a) levels and risk of future coronary heart disease: large-scale prospective data. Arch Intern Med. 2008;168:598–608.

    Article  CAS  Google Scholar 

  18. Kamstrup PR, Tybjaerg-Hansen A, Nordestgaard BG. Extreme lipoprotein(a) levels and improved cardiovascular risk prediction. J Am Coll Cardiol. 2013;61:1146–56.

    Article  CAS  Google Scholar 

  19. Clarke R, Peden JF, Hopewell JC, Kyriakou T, Goel A, Heath SC, et al. Genetic variants associated with Lp(a) lipoprotein level and coronary disease. N. Engl J Med. 2009;361:2518–28.

    Article  CAS  Google Scholar 

  20. Consortium CAD, Deloukas P, Kanoni S, Willenborg C, Farrall M, Assimes TL, et al. Large-scale association analysis identifies new risk loci for coronary artery disease. Nat Genet. 2013;45:25–33.

    Article  Google Scholar 

  21. Emerging Risk Factors C, Erqou S, Kaptoge S, Perry PL, Di Angelantonio E, Thompson A, et al. Lipoprotein(a) concentration and the risk of coronary heart disease, stroke, and nonvascular mortality. JAMA. 2009;302:412–23.

    Article  Google Scholar 

  22. Pare G, Caku A, McQueen M, Anand SS, Enas E, Clarke R, et al. Lipoprotein(a) levels and the risk of myocardial infarction among 7 ethnic groups. Circulation. 2019;139:1472–82.

    Article  CAS  Google Scholar 

  23. Tangvarasittichai S, Pingmuanglaew P, Tangvarasittichai O. Association of elevated serum lipoprotein(a), inflammation, oxidative stress and chronic kidney disease with hypertension in non-diabetes hypertensive patients. Indian J Clin Biochem IJCB. 2016;31:446–51.

    Article  CAS  Google Scholar 

  24. Steinmetz A, Kirklies A, Schlosser G, Cassel W, Peter JH, Ehlenz K, et al. Lipoprotein (a), low-density, intermediate-density lipoprotein, and blood pressure in a young male population. Clin Invest. 1993;71:145–9.

    Article  CAS  Google Scholar 

  25. Sechi LA, Kronenberg F, De Carli S, Falleti E, Zingaro L, Catena C, et al. Association of serum lipoprotein(a) levels and apolipoprotein(a) size polymorphism with target-organ damage in arterial hypertension. JAMA. 1997;277:1689–95.

    Article  CAS  Google Scholar 

  26. Huang Z, Chen C, Li S, Kong F, Shan P, Huang W. Serum markers of endothelial dysfunction and inflammation increase in hypertension with prediabetes mellitus. Genet Test Mol Biomark. 2016;20:322–7.

    Article  CAS  Google Scholar 

  27. Wong WT, Tian XY, Huang Y. Endothelial dysfunction in diabetes and hypertension: cross talk in RAS, BMP4, and ROS-dependent COX-2-derived prostanoids. J Cardiovasc Pharmacol. 2013;61:204–14.

    Article  CAS  Google Scholar 

  28. Jovin IS, Muller-Berghaus G. Interrelationships between the fibrinolytic system and lipoproteins in the pathogenesis of coronary atherosclerosis. Atherosclerosis. 2004;174:225–33.

    Article  CAS  Google Scholar 

  29. Schachinger V, Halle M, Minners J, Berg A, Zeiher AM. Lipoprotein(a) selectively impairs receptor-mediated endothelial vasodilator function of the human coronary circulation. J Am Coll Cardiol. 1997;30:927–34.

    Article  CAS  Google Scholar 

  30. Bergmark C, Dewan A, Orsoni A, Merki E, Miller ER, Shin MJ, et al. A novel function of lipoprotein [a] as a preferential carrier of oxidized phospholipids in human plasma. J Lipid Res. 2008;49:2230–9.

    Article  CAS  Google Scholar 

  31. Marcovina SM, Albers JJ. Lipoprotein (a) measurements for clinical application. J Lipid Res. 2016;57:526–37.

    Article  CAS  Google Scholar 

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Acknowledgements

The authors thank the staff of the Cardiac Catheterization Laboratory at FuWai Hospital for their assistance in performing the studies. The authors also thank all the study investigators, staff, and patients.

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Authors and Affiliations

  1. State Key Laboratory of Cardiovascular Disease, FuWai Hospital, National Center for Cardiovascular Diseases, National Clinical Research Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

    Hui-Hui Liu, Ye-Xuan Cao, Jing-Lu Jin, Yuan-Lin Guo, Cheng-Gang Zhu, Na-Qiong Wu, Qian Dong & Jian-Jun Li

  2. Department of Cardiology, XuanWu Hospital, Capital Medical University, Beijing, China

    Qi Hua

  3. Department of Cardiology, Beijing AnZhen Hospital, Capital Medical University, Beijing, China

    Yan-Fang Li

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  1. Hui-Hui Liu
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Liu, HH., Cao, YX., Jin, JL. et al. Lipoprotein (a), hypertension, and cardiovascular outcomes: a prospective study of patients with stable coronary artery disease. Hypertens Res 44, 1158–1167 (2021). https://doi.org/10.1038/s41440-021-00668-4

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