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

BACKGROUND: Lipoprotein(a) concentrations in plasma are associated with cardiovascular risk in the general population. Whether lipoprotein(a) concentrations or LPA genetic variants predict long-term mortality in patients with established coronary heart disease remains less clear. METHODS: We obtained data from 3313 patients with established coronary heart disease in the Ludwigshafen Risk and Cardiovascular Health (LURIC) study. We tested associations of tertiles of lipoprotein(a) concentration in plasma and two LPA single-nucleotide polymorphisms ([SNPs] rs10455872 and rs3798220) with all-cause mortality and cardiovascular mortality by Cox regression analysis and with severity of disease by generalised linear modelling, with and without adjustment for age, sex, diabetes diagnosis, systolic blood pressure, BMI, smoking status, estimated glomerular filtration rate, LDL-cholesterol concentration, and use of lipid-lowering therapy. Results for plasma lipoprotein(a) concentrations were validated in five independent studies involving 10 195 patients with established coronary heart disease. Results for genetic associations were replicated through large-scale collaborative analysis in the GENIUS-CHD consortium, comprising 106 353 patients with established coronary heart disease and 19 332 deaths in 22 studies or cohorts. FINDINGS: The median follow-up was 9·9 years. Increased severity of coronary heart disease was associated with lipoprotein(a) concentrations in plasma in the highest tertile (adjusted hazard radio [HR] 1·44, 95% CI 1·14-1·83) and the presence of either LPA SNP (1·88, 1·40-2·53). No associations were found in LURIC with all-cause mortality (highest tertile of lipoprotein(a) concentration in plasma 0·95, 0·81-1·11 and either LPA SNP 1·10, 0·92-1·31) or cardiovascular mortality (0·99, 0·81-1·2 and 1·13, 0·90-1·40, respectively) or in the validation studies. INTERPRETATION: In patients with prevalent coronary heart disease, lipoprotein(a) concentrations and genetic variants showed no associations with mortality. We conclude that these variables are not useful risk factors to measure to predict progression to death after coronary heart disease is established. FUNDING: Seventh Framework Programme for Research and Technical Development (AtheroRemo and RiskyCAD), INTERREG IV Oberrhein Programme, Deutsche Nierenstiftung, Else-Kroener Fresenius Foundation, Deutsche Stiftung für Herzforschung, Deutsche Forschungsgemeinschaft, Saarland University, German Federal Ministry of Education and Research, Willy Robert Pitzer Foundation, and Waldburg-Zeil Clinics Isny

Schmierstoffe fuer die 90er Jahre Umwelt, Gesundheit, technischer Fortschritt

SIGLEAvailable from TIB Hannover: RN 6027(1991) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekDEGerman

Tribologie-Fachtagung 2000: Reibung, Schmierung und Verschleiss. Forschung und praktische Anwendungen. Bd. 2: Schmierstoffe und Schmierungstechnik, Maschinenelemente und Antriebstechnik

Vol. 2 comprises 33 papers on lubricants and lubricant technology as well as on machine elements and driving technologies. All papers were read at the Tribology Conference, Goettingen, on September 25 - 27, 2000.SIGLEAvailable from TIB Hannover: RN 6027(2000,2) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekDEGerman

Reibung, Schmierung und Verschleiss

Available from TIB Hannover: RN 6027(1996) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman

Tribologie in der Fahrzeugtechnik Pruefstand, neuartige Werkstoffe, Wartung und Instandhaltung

SIGLETIB Hannover: RN 6027 (1987) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekDEGerman

Tribologie-Fachtagung 2002: Reibung, Schmierung und Verschleiss. Forschung und praktische Anwendungen. Bd. 1: Plenarvortrag, GfT-Foerderpreise, Tribo-talk, Tribologische Systeme, Werkstoffe und Werkstofftechnologien, Duenne Schichten und Oberflaechentechnologien, Zerspanungs- und Umformtechnik

SIGLEAvailable from TIB Hannover: RN 6027(2002,1) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekDEGerman

Tribologie in Theorie und Praxis. Verschleiss von Werkstoffen und Systemen bei Trockenreibung und Grenzschmierung. Schadensfrueherkennung und Verschleissschutz

SIGLECopy held by FIZ Karlsruhe; available from UB/TIB Hannover / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekDEGerman

Reibung, Schmierung und Verschleiss. Bd. 2: Tribologie in der Kraftfahrzeugtechnik Maschinenelemente Fachtagung

Available from TIB Hannover: RN 6027(1998,2) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman