LDL cholesterol still a problem in old age? A Mendelian randomization study

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LDL cholesterol still a problem in old age? A Mendelian randomization study. / Postmus, Iris; Deelen, Joris; Sedaghat, Sanaz; Trompet, Stella; de Craen, Anton Jm; Heijmans, Bastiaan T; Franco, Oscar H; Hofman, Albert; Dehghan, Abbas; Slagboom, P Eline; Westendorp, Rudi Gj; Jukema, J Wouter.

In: International Journal of Epidemiology, Vol. 44, No. 2, 2015, p. 604-612.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Postmus, I, Deelen, J, Sedaghat, S, Trompet, S, de Craen, AJ, Heijmans, BT, Franco, OH, Hofman, A, Dehghan, A, Slagboom, PE, Westendorp, RG & Jukema, JW 2015, 'LDL cholesterol still a problem in old age? A Mendelian randomization study', International Journal of Epidemiology, vol. 44, no. 2, pp. 604-612. https://doi.org/10.1093/ije/dyv031

APA

Postmus, I., Deelen, J., Sedaghat, S., Trompet, S., de Craen, A. J., Heijmans, B. T., ... Jukema, J. W. (2015). LDL cholesterol still a problem in old age? A Mendelian randomization study. International Journal of Epidemiology, 44(2), 604-612. https://doi.org/10.1093/ije/dyv031

Vancouver

Postmus I, Deelen J, Sedaghat S, Trompet S, de Craen AJ, Heijmans BT et al. LDL cholesterol still a problem in old age? A Mendelian randomization study. International Journal of Epidemiology. 2015;44(2):604-612. https://doi.org/10.1093/ije/dyv031

Author

Postmus, Iris ; Deelen, Joris ; Sedaghat, Sanaz ; Trompet, Stella ; de Craen, Anton Jm ; Heijmans, Bastiaan T ; Franco, Oscar H ; Hofman, Albert ; Dehghan, Abbas ; Slagboom, P Eline ; Westendorp, Rudi Gj ; Jukema, J Wouter. / LDL cholesterol still a problem in old age? A Mendelian randomization study. In: International Journal of Epidemiology. 2015 ; Vol. 44, No. 2. pp. 604-612.

Bibtex

@article{09890d51071041b4a7cad9cf4a4ca7bd,
title = "LDL cholesterol still a problem in old age?: A Mendelian randomization study",
abstract = "BACKGROUND: Observational studies in older subjects have shown no or inverse associations between cholesterol levels and mortality. However, in old age plasma low-density lipoprotein cholesterol (LDL-C) may not reflect the lifetime level due to reverse causality, and hence the risk may be underestimated. In the current study, we used an LDL genetic risk score (GRS) to overcome this problem.METHODS: A weighted GRS was created using 51 single nucleotide polymorphisms associated with LDL-C levels. The LDL GRS was calculated in three Dutch cohorts: the Leiden Longevity Study (LLS) (n = 3270), the Leiden 85-plus study (n = 316) and the Rotterdam Study (n = 4035). We assessed the association between the LDL GRS and LDL-C levels, chronological age, familial longevity and mortality.RESULTS: Up to 90 years of age, in each age stratum individuals with high LDL GRS had higher LDL-C levels (P = 0.010 to P = 1.1 x 10-16). The frequency of LDL-increasing alleles decreased with increasing age [β = -0.021 (SE = 0.01) per year, P = 0.018]. Moreover, individuals with a genetic predisposition for longevity had significantly lower LDL GRS compared with age-matched individuals of the general population [LLS nonagenarians vs > 90 years: β = 0.73 (SE = 0.33), P = 0.029, LLS offspring vs partners: β = 0.66 (SE = 0.23), P = 0.005]. In longitudinal analysis, high GRS was associated with increased all-cause mortality in individuals > 90 years, with a 13{\%} increased risk in individuals with the highest LDL GRS (P-trend = 0.043).CONCLUSION: Results of the current study indicate that a genetic predisposition to high LDL-C levels contributes to mortality throughout life, including in the oldest old, and a beneficial LDL genetic risk profile is associated with familial longevity.",
author = "Iris Postmus and Joris Deelen and Sanaz Sedaghat and Stella Trompet and {de Craen}, {Anton Jm} and Heijmans, {Bastiaan T} and Franco, {Oscar H} and Albert Hofman and Abbas Dehghan and Slagboom, {P Eline} and Westendorp, {Rudi Gj} and Jukema, {J Wouter}",
note = "{\circledC} The Author 2015; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.",
year = "2015",
doi = "10.1093/ije/dyv031",
language = "English",
volume = "44",
pages = "604--612",
journal = "International Journal of Epidemiology",
issn = "0300-5771",
publisher = "Oxford University Press",
number = "2",

}

RIS

TY - JOUR

T1 - LDL cholesterol still a problem in old age?

T2 - A Mendelian randomization study

AU - Postmus, Iris

AU - Deelen, Joris

AU - Sedaghat, Sanaz

AU - Trompet, Stella

AU - de Craen, Anton Jm

AU - Heijmans, Bastiaan T

AU - Franco, Oscar H

AU - Hofman, Albert

AU - Dehghan, Abbas

AU - Slagboom, P Eline

AU - Westendorp, Rudi Gj

AU - Jukema, J Wouter

N1 - © The Author 2015; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.

PY - 2015

Y1 - 2015

N2 - BACKGROUND: Observational studies in older subjects have shown no or inverse associations between cholesterol levels and mortality. However, in old age plasma low-density lipoprotein cholesterol (LDL-C) may not reflect the lifetime level due to reverse causality, and hence the risk may be underestimated. In the current study, we used an LDL genetic risk score (GRS) to overcome this problem.METHODS: A weighted GRS was created using 51 single nucleotide polymorphisms associated with LDL-C levels. The LDL GRS was calculated in three Dutch cohorts: the Leiden Longevity Study (LLS) (n = 3270), the Leiden 85-plus study (n = 316) and the Rotterdam Study (n = 4035). We assessed the association between the LDL GRS and LDL-C levels, chronological age, familial longevity and mortality.RESULTS: Up to 90 years of age, in each age stratum individuals with high LDL GRS had higher LDL-C levels (P = 0.010 to P = 1.1 x 10-16). The frequency of LDL-increasing alleles decreased with increasing age [β = -0.021 (SE = 0.01) per year, P = 0.018]. Moreover, individuals with a genetic predisposition for longevity had significantly lower LDL GRS compared with age-matched individuals of the general population [LLS nonagenarians vs > 90 years: β = 0.73 (SE = 0.33), P = 0.029, LLS offspring vs partners: β = 0.66 (SE = 0.23), P = 0.005]. In longitudinal analysis, high GRS was associated with increased all-cause mortality in individuals > 90 years, with a 13% increased risk in individuals with the highest LDL GRS (P-trend = 0.043).CONCLUSION: Results of the current study indicate that a genetic predisposition to high LDL-C levels contributes to mortality throughout life, including in the oldest old, and a beneficial LDL genetic risk profile is associated with familial longevity.

AB - BACKGROUND: Observational studies in older subjects have shown no or inverse associations between cholesterol levels and mortality. However, in old age plasma low-density lipoprotein cholesterol (LDL-C) may not reflect the lifetime level due to reverse causality, and hence the risk may be underestimated. In the current study, we used an LDL genetic risk score (GRS) to overcome this problem.METHODS: A weighted GRS was created using 51 single nucleotide polymorphisms associated with LDL-C levels. The LDL GRS was calculated in three Dutch cohorts: the Leiden Longevity Study (LLS) (n = 3270), the Leiden 85-plus study (n = 316) and the Rotterdam Study (n = 4035). We assessed the association between the LDL GRS and LDL-C levels, chronological age, familial longevity and mortality.RESULTS: Up to 90 years of age, in each age stratum individuals with high LDL GRS had higher LDL-C levels (P = 0.010 to P = 1.1 x 10-16). The frequency of LDL-increasing alleles decreased with increasing age [β = -0.021 (SE = 0.01) per year, P = 0.018]. Moreover, individuals with a genetic predisposition for longevity had significantly lower LDL GRS compared with age-matched individuals of the general population [LLS nonagenarians vs > 90 years: β = 0.73 (SE = 0.33), P = 0.029, LLS offspring vs partners: β = 0.66 (SE = 0.23), P = 0.005]. In longitudinal analysis, high GRS was associated with increased all-cause mortality in individuals > 90 years, with a 13% increased risk in individuals with the highest LDL GRS (P-trend = 0.043).CONCLUSION: Results of the current study indicate that a genetic predisposition to high LDL-C levels contributes to mortality throughout life, including in the oldest old, and a beneficial LDL genetic risk profile is associated with familial longevity.

U2 - 10.1093/ije/dyv031

DO - 10.1093/ije/dyv031

M3 - Journal article

VL - 44

SP - 604

EP - 612

JO - International Journal of Epidemiology

JF - International Journal of Epidemiology

SN - 0300-5771

IS - 2

ER -

ID: 140395369