Skip to main content
Erschienen in: Clinical Research in Cardiology 12/2019

04.04.2019 | Original Paper

Low serum lathosterol levels associate with fatal cardiovascular disease and excess all-cause mortality: a prospective cohort study

verfasst von: Oliver Weingärtner, Dieter Lütjohann, Sven Meyer, Arne Fuhrmann, Bodo Cremers, Sarah Seiler-Mußler, Hans-F. Schött, Anja Kerksiek, Silvia Friedrichs, Ursula Ulbricht, Adam Zawada, Ulrich Laufs, P. Christian Schulze, Bruno Scheller, Danilo Fliser, Michael Böhm, Eric Sijbrands, Gunnar H. Heine

Erschienen in: Clinical Research in Cardiology | Ausgabe 12/2019

Einloggen, um Zugang zu erhalten

Abstract

Importance

A more precise identification of patients at “high cardiovascular risk” is preeminent in cardiovascular risk stratification.

Objective

To investigate the relationships between markers of cholesterol homeostasis, cardiovascular events and all-cause mortality.

Design, setting and participants

We quantified markers of cholesterol homeostasis by gas chromatography–mass spectrometry in 377 subjects with suspected coronary artery disease, who were not on lipid-lowering drugs at baseline. All patients were followed for occurrence of cardiovascular events and mortality over a period of 4.9 +/− 1.7 years. The standardized mortality ratio (SMR) was calculated as the ratio of the observed and the expected deaths based on the death rates of the Regional Databases Germany, and Poisson regression (rate ratio, RR) was used to compare subgroups. The SMR and RR were standardized for sex, age category and calendar period. In addition, Cox regression (Hazard ratio, HR) was used to determine the effect of co-variables on (cardiovascular) mortality within the cohort.

Main outcomes

Cardiovascular events, cardiovascular mortality and all-cause mortality.

Results

A total of 42 deaths were observed in 1818 person-years corresponding with an SMR of 0.99 (95% CI 0.71–1.33; p = 0.556). A fatal cardiovascular event occurred in 26 patients. Lower levels of lathosterol were associated with increased cardiovascular mortality (HR 1.59; 95% CI: 1.16–2.17; p = 0.004) and excess all-cause mortality (HR 1.41; 95% CI: 1.09–1.85; p = 0.011). Lower lathosterol tertile compared to the adjacent higher tertile was associated with 1.6 times higher all-cause mortality risk (RR 1.60; 95% CI 1.07–2.40; p for trend = 0.022). This corresponded with a 2.3 times higher mortality risk of a lathosterol–LDL ratio equal to or below the median (RR 2.29; 95% CI 1.19–4.43; p = 0.013). None of the other cholesterol homeostasis markers were associated with cardiovascular and all-cause mortality.

Conclusions

In patients not on lipid-lowering agents, low serum lathosterol correlated with increased risk of cardiovascular events and excess all-cause mortality.
Literatur
1.
Zurück zum Zitat Ference BA, Ginsberg HN, Graham I et al (2017) Low-density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European Atherosclerosis Society Consensus Panel. Eur Heart J 38(32):2459–2472CrossRef Ference BA, Ginsberg HN, Graham I et al (2017) Low-density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European Atherosclerosis Society Consensus Panel. Eur Heart J 38(32):2459–2472CrossRef
2.
Zurück zum Zitat Fulcher J, O’Connell R, Voysey M et al (2015) Efficacy and safety of LDL-lowering therapy among men and women: meta-analysis of individual data from 174,000 participants in 27 randomised trials. Lancet 385(9976):1397–1405CrossRef Fulcher J, O’Connell R, Voysey M et al (2015) Efficacy and safety of LDL-lowering therapy among men and women: meta-analysis of individual data from 174,000 participants in 27 randomised trials. Lancet 385(9976):1397–1405CrossRef
3.
Zurück zum Zitat Weingärtner O, Lütjohann D, Böhm M, Laufs U (2010) Relationship between cholesterol synthesis and intestinal absorption is associated with cardiovascular risk. Atherosclerosis. 210:362–365CrossRef Weingärtner O, Lütjohann D, Böhm M, Laufs U (2010) Relationship between cholesterol synthesis and intestinal absorption is associated with cardiovascular risk. Atherosclerosis. 210:362–365CrossRef
4.
Zurück zum Zitat Miettinen TA, Gylling H, Strandberg T, Sarna S (1998) Baseline serum cholestanol as predictor of recurrent coronary events in subgroup of Scandinavian simvastatin survival study. Finnish 4S Investigators. BMJ 316(7138):1127–1130CrossRef Miettinen TA, Gylling H, Strandberg T, Sarna S (1998) Baseline serum cholestanol as predictor of recurrent coronary events in subgroup of Scandinavian simvastatin survival study. Finnish 4S Investigators. BMJ 316(7138):1127–1130CrossRef
5.
Zurück zum Zitat Weingärtner O, Weingärtner N, Scheller B et al (2009) Alterations in cholesterol homeostasis are associated with coronary heart disease in patients with aortic stenosis. Coron Artery Dis 2009:276–282 Weingärtner O, Weingärtner N, Scheller B et al (2009) Alterations in cholesterol homeostasis are associated with coronary heart disease in patients with aortic stenosis. Coron Artery Dis 2009:276–282
6.
Zurück zum Zitat Matthan NR, Pencina M, LaRocque JM et al (2009) Alterations in cholesterol absorption/synthesis markers characterize Framingham offspring study participants with CHD. J Lipid Res 50(9):1927–1935CrossRef Matthan NR, Pencina M, LaRocque JM et al (2009) Alterations in cholesterol absorption/synthesis markers characterize Framingham offspring study participants with CHD. J Lipid Res 50(9):1927–1935CrossRef
7.
Zurück zum Zitat Silbernagel G, Fauler G, Hoffmann MM et al (2010) The associations of cholesterol metabolism and plasma plant sterols with all-cause and cardiovascular mortality. J Lipid Res 51(8):2384–2393CrossRef Silbernagel G, Fauler G, Hoffmann MM et al (2010) The associations of cholesterol metabolism and plasma plant sterols with all-cause and cardiovascular mortality. J Lipid Res 51(8):2384–2393CrossRef
8.
Zurück zum Zitat Rogacev KS, Cremers B, Zawada AM et al (2012) CD14++ CD16+ monocytes independently predict cardiovascular events: a cohort study of 951 patients referred for elective coronary angiography. J Am Coll Cardiol 60(16):1512–1520CrossRef Rogacev KS, Cremers B, Zawada AM et al (2012) CD14++ CD16+ monocytes independently predict cardiovascular events: a cohort study of 951 patients referred for elective coronary angiography. J Am Coll Cardiol 60(16):1512–1520CrossRef
9.
Zurück zum Zitat van Himbergen TM, Matthan NR, Resteghini NA et al (2009) Comparison of the effects of maximal dose atorvastatin and rosuvastatin therapy on cholesterol synthesis and absorption markers. J Lipid Res 50(4):730–739CrossRef van Himbergen TM, Matthan NR, Resteghini NA et al (2009) Comparison of the effects of maximal dose atorvastatin and rosuvastatin therapy on cholesterol synthesis and absorption markers. J Lipid Res 50(4):730–739CrossRef
10.
Zurück zum Zitat Mackay DS, Jones PJ, Myrie SB, Plat J, Lutjohann D (2014) Methodological considerations for the harmonization of non-cholesterol sterol bio-analysis. J Chromatogr B Anal Technol Biomed Life Sci. 957:116–122CrossRef Mackay DS, Jones PJ, Myrie SB, Plat J, Lutjohann D (2014) Methodological considerations for the harmonization of non-cholesterol sterol bio-analysis. J Chromatogr B Anal Technol Biomed Life Sci. 957:116–122CrossRef
11.
Zurück zum Zitat Thelen KM, Rentsch KM, Gutteck U et al (2006) Brain cholesterol synthesis in mice is affected by high dose of simvastatin but not of pravastatin. J Pharmacol Exp Ther 316(3):1146–1152CrossRef Thelen KM, Rentsch KM, Gutteck U et al (2006) Brain cholesterol synthesis in mice is affected by high dose of simvastatin but not of pravastatin. J Pharmacol Exp Ther 316(3):1146–1152CrossRef
12.
Zurück zum Zitat Brown MS, Dana SE, Goldstein JL (1973) Regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in human fibroblasts by lipoproteins. Proc Natl Acad Sci USA 70(7):2162–2166CrossRef Brown MS, Dana SE, Goldstein JL (1973) Regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in human fibroblasts by lipoproteins. Proc Natl Acad Sci USA 70(7):2162–2166CrossRef
13.
Zurück zum Zitat Weingärtner O, Lütjohann D, Elsässer A (2016) Personalize and optimize lipid-lowering therapies. J Am Coll Cardiol. 68(3):325–326CrossRef Weingärtner O, Lütjohann D, Elsässer A (2016) Personalize and optimize lipid-lowering therapies. J Am Coll Cardiol. 68(3):325–326CrossRef
15.
Zurück zum Zitat Yamaguchi J, Kawada-Watanabe E, Koyanagi R et al (2018) Baseline serum sitosterol level as predictor of adverse clinical events in acute coronary syndrome patients with dyslipidaemia: a sub-analysis of HIJ-PROPER. Atherosclerosis. 274:139–145CrossRef Yamaguchi J, Kawada-Watanabe E, Koyanagi R et al (2018) Baseline serum sitosterol level as predictor of adverse clinical events in acute coronary syndrome patients with dyslipidaemia: a sub-analysis of HIJ-PROPER. Atherosclerosis. 274:139–145CrossRef
Metadaten
Titel
Low serum lathosterol levels associate with fatal cardiovascular disease and excess all-cause mortality: a prospective cohort study
verfasst von
Oliver Weingärtner
Dieter Lütjohann
Sven Meyer
Arne Fuhrmann
Bodo Cremers
Sarah Seiler-Mußler
Hans-F. Schött
Anja Kerksiek
Silvia Friedrichs
Ursula Ulbricht
Adam Zawada
Ulrich Laufs
P. Christian Schulze
Bruno Scheller
Danilo Fliser
Michael Böhm
Eric Sijbrands
Gunnar H. Heine
Publikationsdatum
04.04.2019
Verlag
Springer Berlin Heidelberg
Erschienen in
Clinical Research in Cardiology / Ausgabe 12/2019
Print ISSN: 1861-0684
Elektronische ISSN: 1861-0692
DOI
https://doi.org/10.1007/s00392-019-01474-2

Weitere Artikel der Ausgabe 12/2019

Clinical Research in Cardiology 12/2019 Zur Ausgabe

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Therapiestart mit Blutdrucksenkern erhöht Frakturrisiko

25.04.2024 Hypertonie Nachrichten

Beginnen ältere Männer im Pflegeheim eine Antihypertensiva-Therapie, dann ist die Frakturrate in den folgenden 30 Tagen mehr als verdoppelt. Besonders häufig stürzen Demenzkranke und Männer, die erstmals Blutdrucksenker nehmen. Dafür spricht eine Analyse unter US-Veteranen.

Adipositas-Medikament auch gegen Schlafapnoe wirksam

24.04.2024 Adipositas Nachrichten

Der als Antidiabetikum sowie zum Gewichtsmanagement zugelassene Wirkstoff Tirzepatid hat in Studien bei adipösen Patienten auch schlafbezogene Atmungsstörungen deutlich reduziert, informiert der Hersteller in einer Vorab-Meldung zum Studienausgang.

Komplette Revaskularisation bei Infarkt: Neue Studie setzt ein Fragezeichen

24.04.2024 ACC 2024 Nachrichten

Eine FFR-gesteuerte komplette Revaskularisation war in einer Studie bei Patienten mit akutem Myokardinfarkt und koronarer Mehrgefäßerkrankung klinisch nicht wirksamer als eine alleinige Revaskularisation der Infarktarterie.

Update Kardiologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.