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

  • Oliver WeingärtnerEmail author
  • 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
Original Paper
  • 175 Downloads

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.

Keywords

Cholesterol Synthesis Absorption Mortality Cardiovascular events 

Notes

Acknowledgements

This study was supported by an unrestricted research grant from Unilever, Vlaardingen, the Netherlands.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Oliver Weingärtner
    • 1
    • 2
    Email author
  • Dieter Lütjohann
    • 1
    • 3
  • Sven Meyer
    • 2
  • Arne Fuhrmann
    • 3
  • Bodo Cremers
    • 5
  • Sarah Seiler-Mußler
    • 7
  • Hans-F. Schött
    • 3
    • 4
  • Anja Kerksiek
    • 3
  • Silvia Friedrichs
    • 3
  • Ursula Ulbricht
    • 7
  • Adam Zawada
    • 7
  • Ulrich Laufs
    • 5
  • P. Christian Schulze
    • 1
  • Bruno Scheller
    • 5
  • Danilo Fliser
    • 7
  • Michael Böhm
    • 5
  • Eric Sijbrands
    • 6
  • Gunnar H. Heine
    • 7
  1. 1.Klinik für Innere Medizin I, Universitätsklinikum JenaFriedrich-Schiller-Universität JenaJenaGermany
  2. 2.Abteilung für Kardiologie, Klinikum OldenburgEuropean Medical School Oldenburg-GroningenOldenburgGermany
  3. 3.Institut für Klinische Pharmakologie und Klinische ChemieUniversitätsklinikum BonnBonnGermany
  4. 4.Leibniz-Institut für Analytische Wissenschaften-ISAS-e.V.DortmundGermany
  5. 5.Klinik für Innere Medizin III, Abteilung für Kardiologie, Angiologie und Internistische IntensivmedizinUniversitätsklinikum des SaarlandesHomburgGermany
  6. 6.Department of Vascular Genetics, Department of Internal MedicineErasmus MC-University Medical Center RotterdamRotterdamThe Netherlands
  7. 7.Klinik für Innere Medizin IV, Abteilung für Nieren-und HochdruckkrankheitenUniversitätsklinikum des SaarlandesHomburgGermany

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