Advertisement

Serum lipoprotein(a) levels and apolipoprotein(a) isoform size and risk for first-ever acute ischaemic nonembolic stroke in elderly individuals

      Abstract

      In a population-based case-control study, we investigated the association of acute ischaemic stroke with lipoprotein(a) (Lp(a)) levels and apolipoprotein (Apo) (a) isoform size in subjects aged older than 70 years. A total of 163 patients with a first-ever-in-a-lifetime acute ischaemic/nonembolic stroke and 166 controls were included.
      Compared to controls, stroke patients exhibited higher Lp(a) concentrations (median value, 12.2 mg/dl versus 6.4 mg/dl, p < 0.001) and a higher frequency of small Apo(a) isoforms (44.2% versus 29.5%, p < 0.01). Multivariate logistic regression analysis showed a significant association of acute ischaemic stroke with Lp(a) levels [adjusted odds ratio (OR), 1.37, 95% CI (1.12–1.67); p = 0.002], and small Apo(a) isoform size [OR, 1.74 (1.10–3.03); p = 0.04]. Compared to subjects with Lp(a) levels in the lowest quintile, those within the highest quintile had a 3.2-times adjusted risk to suffer an acute ischaemic/nonembolic stroke (1.60–6.62, 95% CI; p < 0.001). Furthermore, analysis of interaction between lipid variables revealed that in the presence of elevated Lp(a) levels the inverse relationship between HDL-cholesterol levels and ischaemic stroke was negated [OR, 1.01 (1.00–1.03); p = 0.015].
      Our study suggests that determination of Lp(a) levels and Apo(a) isoform size may be important in identifying elderly individuals at risk of ischaemic stroke independently of other risk factors and concurrent metabolic derangements.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Atherosclerosis
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Bonita R.
        Epidemiology of stroke.
        Lancet. 1992; 339: 342-344
        • Futterman L.G.
        • Lemberg L.
        Stroke risk, cholesterol and statins.
        Am J Crit Care. 1999; 8: 416-419
        • Milionis H.J.
        • Liberopoulos E.
        • Goudevenos J.
        • et al.
        Risk factors for first-ever acute ischemic non-embolic stroke in elderly individuals.
        Int J Cardiol. 2005; 99: 269-275
        • Ariyo A.A.
        • Thach C.
        • Tracy R.
        Lp(a) lipoprotein, vascular disease, and mortality in the elderly.
        N Engl J Med. 2003; 349: 2108-2115
        • Gaw A.
        • Murray H.M.
        • Brown E.A.
        Plasma lipoprotein(a) [Lp(a)] concentrations and cardiovascular events in the elderly: evidence from the prospective study of pravastatin in the elderly at risk (PROSPER).
        Atherosclerosis. 2005; 180: 381-388
        • Scanu A.M.
        Lp(a) lipoprotein—coping with heterogeneity.
        N Engl J Med. 2003; 349: 2089-2090
        • Milionis H.J.
        • Rizos E.
        • Goudevenos J.
        • et al.
        Components of the metabolic syndrome and risk for first-ever acute ischemic nonembolic stroke in elderly subjects.
        Stroke. 2005; 36: 1372-1376
        • Milionis H.J.
        • Efstathiadou Z.
        • Tselepis A.D.
        • et al.
        Lipoprotein(a) levels and apolipoprotein(a) isoform size in patients with subclinical hypothyroidism: effect of treatment with levothyroxine.
        Thyroid. 2003; 13: 365-369
        • Fried L.P.
        • Borhani N.O.
        • Enright P.
        • et al.
        The cardiovascular health study: design and rationale.
        Ann Epidemiol. 1991; 1: 263-276
        • Denti L.
        • Cecchetti A.
        • Annoni V.
        • et al.
        The role of lipid profile in determining the risk of ischemic stroke in the elderly: a case-control study.
        Arch Gerontol Geriatr. 2003; 37: 51-62
        • Bostom A.G.
        • Cupples L.A.
        • Jenner J.L.
        • et al.
        Elevated plasma lipoprotein(a) and coronary heart disease in men aged 55 years and younger. A prospective study.
        Jama. 1996; 276: 544-548
        • Milionis H.J.
        • Winder A.F.
        • Mikhailidis D.P.
        Lipoprotein(a) and stroke.
        J Clin Pathol. 2000; 53: 487-496
        • Boerwinkle E.
        • Leffert C.C.
        • Lin J.
        • et al.
        Apolipoprotein(a) gene accounts for greater than 90% of the variation in plasma lipoprotein(a) concentrations.
        J Clin Invest. 1992; 90: 52-60
        • Gaw A.
        • Brown E.A.
        • Ford I.
        Impact of apo(a) length polymorphism and the control of plasma Lp(a) concentrations: evidence for a threshold effect.
        Arterioscler Thromb Vasc Biol. 1998; 18: 1870-1876
        • Shintani S.
        • Kikuchi S.
        • Hamaguchi H.
        • et al.
        High serum lipoprotein(a) levels are an independent risk factor for cerebral infarction.
        Stroke. 1993; 24: 965-969
        • Kario K.
        • Matsuo T.
        • Imiya M.
        • et al.
        Close relation between lipoprotein(a) levels and atherothrombotic disease in Japanese subjects >75 years of age.
        Am J Cardiol. 1994; 73: 1187-1190
        • Kario K.
        • Matsuo T.
        • Kobayashi H.
        • et al.
        Silent cerebral infarction is associated with hypercoagulability, endothelial cell damage, and high Lp(a) levels in elderly Japanese.
        Arterioscler Thromb Vasc Biol. 1996; 16: 734-741
        • Nguyen T.T.
        • Ellefson R.D.
        • Hodge D.O.
        • et al.
        Predictive value of electrophoretically detected lipoprotein(a) for coronary heart disease and cerebrovascular disease in a community-based cohort of 9936 men and women.
        Circulation. 1997; 96: 1390-1397
        • Ridker P.M.
        • Stampfer M.J.
        • Hennekens C.H.
        Plasma concentration of lipoprotein(a) and the risk of future stroke.
        JAMA. 1995; 273: 1269-1273
        • Schreiner P.J.
        • Chambless L.E.
        • Brown S.A.
        • et al.
        Lipoprotein(a) as a correlate of stroke and transient ischemic attack prevalence in a biracial cohort: the ARIC study. Atherosclerosis risk in communities.
        Ann Epidemiol. 1994; 4: 351-359
        • Misirli H.
        • Somay G.
        • Ozbal N.
        • et al.
        Relation of lipid and lipoprotein(a) to ischaemic stroke.
        J Clin Neurosci. 2002; 9: 127-132
        • Alfthan G.
        • Pekkanen J.
        • Jauhiainen M.
        • et al.
        Relation of serum homocysteine and lipoprotein(a) concentrations to atherosclerotic disease in a prospective Finnish population-based study.
        Atherosclerosis. 1994; 106: 9-19
        • Glader C.A.
        • Stegmayr B.
        • Boman J.
        • et al.
        Chlamydia pneumoniae antibodies and high lipoprotein(a) levels do not predict ischemic cerebral infarctions. Results from a nested case-control study in Northern Sweden.
        Stroke. 1999; 30: 2013-2018
        • Paultre F.
        • Tuck C.H.
        • Boden-Albala B.
        • et al.
        Relation of Apo(a) size to carotid atherosclerosis in an elderly multiethnic population.
        Arterioscler Thromb Vasc Biol. 2002; 22: 141-146
        • Cremer P.
        • Nagel D.
        • Labrot B.
        • et al.
        Lipoprotein Lp(a) as predictor of myocardial infarction in comparison to fibrinogen, LDL cholesterol and other risk factors: results from the prospective Gottingen Risk Incidence and Prevalence Study (GRIPS).
        Eur J Clin Invest. 1994; 24: 444-453
        • von Eckardstein A.
        • Schulte H.
        • Cullen P.
        • et al.
        Lipoprotein(a) further increases the risk of coronary events in men with high global cardiovascular risk.
        J Am Coll Cardiol. 2001; 37: 434-439
        • Luc G.
        • Bard J.M.
        • Arveiler D.
        • et al.
        Lipoprotein(a) as a predictor of coronary heart disease: the PRIME study.
        Atherosclerosis. 2002; 163: 377-384
        • Margaglione M.
        • DiMinno G.
        • Grandone E.
        • et al.
        Plasma lipoprotein(a) levels in subjects attending a metabolic ward. Discrimination between individuals with and without a history of ischemic stroke.
        Arterioscler Thromb Vasc Biol. 1996; 16: 120-128
      1. MRC/BHF heart protection study of cholesterol lowering with simvastatin in 20, 536 high-risk individuals: a randomised placebo-controlled trial. Lancet 2002; 360:7–22.

        • Shepherd J.
        • Blauw G.J.
        • Murphy M.B.
        • et al.
        Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial.
        Lancet. 2002; 360: 1623-1630