Lipoprotien(a) and Stroke 

• Carotid artery disease is an important preventable risk factor for stroke, which is a leading cause of mortality and long-term disability. Numerous studies have demonstrated elevated Lipoprotein(a) (Lp(a)) level to be a strong risk factor for the presence and severity of cerebrovascular disease and premature stroke in diverse populations.^1-5

• High Lp(a) level is highly correlated with carotid and coronary artery plaque burden and it is the cause and not the consequence of the disease.^6-10

• In Japanese and Chinese populations, stroke is the predominant form of vascular disease and Lp(a) has a stronger relationship to premature stroke than CAD (coronary artery disease) in these populations.^{3, 11-13}

• Lp(a) is an important risk factor for premature stroke among Asian Indians and south Asians especially in those younger than 40 years of age.^{2, 3, 12, 14}

• Lp(a) is a strong risk factor for stroke in neonates and children; the risk is further increased with concomitant thrombophilic factors such as Factor V Lieden or protein C deficiency.^15-18

• Screening for Lp(a) may help explain many cases of unexplained stroke, heart attack, as well as venous thromboembolism in children and young adults.⁷

• The Heart Protection Study did not show any association of Lp(a) with stroke but confirmed the association with both incident and prevalent CAD and peripheral vascular disease.¹⁹

Sources

1. Schreiner PJ, Morrisett JD, Sharrett AR, et al. Lipoprotein[a] as a risk factor for preclinical atherosclerosis. Arterioscler Thromb. Jun 1993;13(6):826-833.

2. Christopher R, Kailasanatha KM, Nagaraja D, Tripathi M. Case-control study of serum lipoprotein(a) and apolipoproteins A-I and B in stroke in the young. Acta Neurol Scand. Aug 1996;94(2):127-130.

3. Nagayama M, Shinohara Y, Nagayama T. Lipoprotein(a) and ischemic cerebrovascular disease in young adults. Stroke. Jan 1994;25(1):74-78.

4. Jurgens G, Taddie-Peters W, Koltringer P, et al. Lipoprotein(a) serum concentration and apolipoprotein(a) phenotype correlate with the severity and presence of ischemic cerebrovascular disease. Stroke. 1995;6:1841 – 1848.

5. Woo J, Lau E, Lam CW, et al. Hypertension, lipoprotein(a), and apolipoprotein A-I as risk factors for stroke in the Chinese. Stroke. Feb 1991;22(2):203-208.

6. Kamstrup PR, Tybjaerg-Hansen A, Steffensen R, Nordestgaard BG. Genetically elevated lipoprotein(a) and increased risk of myocardial infarction. JAMA. Jun 10 2009;301(22):2331-2339.

7. Ronald J, Rajagopalan R, Cerrato F, et al. Genetic Variation in LPAL2, LPA, and PLG Predicts Plasma Lipoprotein(a) Level and Carotid Artery Disease Risk. Stroke. Jan 2011;42(1):2-9.

8. Klein JH, Hegele RA, Hackam DG, Koschinsky ML, Huff MW, Spence JD. Lipoprotein(a) is associated differentially with carotid stenosis, occlusion, and total plaque area. Arteriosclerosis, thrombosis, and vascular biology. Oct 2008;28(10):1851-1856.

9. Ohira T, Schreiner PJ, Morrisett JD, Chambless LE, Rosamond WD, Folsom AR. Lipoprotein(a) and incident ischemic stroke: the Atherosclerosis Risk in Communities (ARIC) study. Stroke. Jun 2006;37(6):1407-1412.

10. Kim BS, Jung HS, Bang OY, Chung CS, Lee KH, Kim GM. Elevated serum lipoprotein(a) as a potential predictor for combined intracranial and extracranial artery stenosis in patients with ischemic stroke. Atherosclerosis. Oct 2010;212(2):682-688.

11. Murai A, Miyahara T, Fujimoto N, Matsuda M, Kameyama M. Lp(a) lipoprotein as a risk factor for coronary heart disease and cerebral infarction. Atherosclerosis. 1986;59(2):199-204.

12. Shintani S, Kikuchi S, Hamaguchi H, Shiigai T. High serum lipoprotein(a) levels are an independent risk factor for cerebral infarction. Stroke. 1993;24(7):965-969.

13. Sone H, Tanaka S, Iimuro S, et al. Long-term lifestyle intervention lowers the incidence of stroke in Japanese patients with type 2 diabetes: a nationwide multicentre randomised controlled trial (the Japan Diabetes Complications Study). Diabetologia. Mar 2010;53(3):419-428.

14. Sharobeem KM, Patel JV, Ritch AE, Lip GY, Gill PS, Hughes EA. Elevated lipoprotein (a) and apolipoprotein B to AI ratio in South Asian patients with ischaemic stroke. International journal of clinical practice. Nov 2007;61(11):1824-1828.

15. Nowak-Gottl U, Junker R, Hartmeier M, et al. Increased lipoprotein(a) is an important risk factor for venous thromboembolism in childhood. Circulation. 1999;100(7):743-748.

16. Strater R, Becker S, von Eckardstein A, et al. Prospective assessment of risk factors for recurrent stroke during childhood–a 5-year follow-up study. Lancet. Nov 16 2002;360(9345):1540-1545.

17. Renaud C, Bonneau C, Presles E, et al. Lipoprotein (a), birth weight and neonatal stroke. Neonatology. 2010;98(3):225-228.

18. Teber S, Deda G, Akar N, Soylu K. Lipoprotein (a) levels in childhood arterial ischemic stroke. Clin Appl Thromb Hemost. Apr 2010;16(2):214-217.

19. Hopewell JC, Clarke R, Parish S, et al. Lipoprotein(a) genetic variants associated with coronary and peripheral vascular disease but not with stroke risk in the Heart Protection Study. Circ Cardiovasc Genet. Feb 1 2011;4(1):68-73.