Associations between medication use and homocysteine levels in an older population, and potential mediation by vitamin B12 and folate: data from the B-PROOF study

A.C. Ham, A.W. Enneman, S.C. van Dijk, J.P. van Wijngaarden, N.L. van der Zwaluw, E.M. Brouwer, R.A.M. Dhonukshe-Rutten, C.P.G.M. de Groot, R.F. Witkamp

Research output: Contribution to journalArticleAcademicpeer-review

7 Citations (Scopus)

Abstract

Background Elevated homocysteine levels are a risk indicator for cardiovascular disease, fractures and cognitive decline. Previous studies indicated associations between homocysteine levels and medication use, including antihypertensive, lipid-lowering and antidiabetic medication. However, results were often contradictory and inconclusive. Our objective was to study the associations established previously in more detail by sub-classifying medication groups, and investigate the potential mediating role of vitamin B12 and folate status. Materials and Methods Baseline data from the B-PROOF (B-vitamins for the PRevention Of Osteoporotic Fractures) study were used. We included 2,912 participants aged =65 years, with homocysteine levels of 12–50 µmol/L and creatinine levels =150 µmol/L, for whom self-reported medication data were available. We used multivariable linear regression models and analysis of covariance to assess the association between medication use and plasma homocysteine levels, and the potential mediation by serum vitamin B12 and folate. Results The mean age was 74 years (standard deviation, 6.5), 50 % were women, and median homocysteine levels were 14 µmol/L [interquartile range, 13–17 µmol/L]. Higher mean homocysteine levels were observed in users vs. non-users for diuretics (15.2 vs. 14.9, p = 0.043), high-ceiling sulphonamide diuretics (16.0 vs. 14.9, p <0.001), medication acting via the renin-angiotensin system (15.2 vs. 14.9, p = 0.029) and metformin (15.6 vs. 15.1, p = 0.006). Non-selective ß-blocker use was associated with lower mean homocysteine levels (14.4 vs. 15.0, p = 0.019). Only this association was mediated by an underlying association with vitamin B12 and folate levels. Conclusion The associations between homocysteine levels and medication use appear to be fairly modest. Our results suggest that medication use is unlikely to contribute to clinically relevant changes in plasma homocysteine levels.
Original languageEnglish
Pages (from-to)611-621
JournalDrugs & Aging
Volume31
Issue number8
DOIs
Publication statusPublished - 2014

Fingerprint

Vitamin B Complex
Osteoporotic Fractures
Homocysteine
Vitamin B 12
Folic Acid
Population
Linear Models
Sodium Potassium Chloride Symporter Inhibitors
Metformin
Sulfonamides
Renin-Angiotensin System
Diuretics
Hypoglycemic Agents
Antihypertensive Agents
Creatinine
Cardiovascular Diseases
Regression Analysis
Lipids

Keywords

  • type-2 diabetes-mellitus
  • plasma homocysteine
  • folic-acid
  • cardiovascular risk
  • parkinsons-disease
  • essential-hypertension
  • serum concentrations
  • c677t polymorphism
  • pharmacy records
  • controlled-trial

Cite this

@article{8d3ba7dd37ca4f08b9479fd31f538d8d,
title = "Associations between medication use and homocysteine levels in an older population, and potential mediation by vitamin B12 and folate: data from the B-PROOF study",
abstract = "Background Elevated homocysteine levels are a risk indicator for cardiovascular disease, fractures and cognitive decline. Previous studies indicated associations between homocysteine levels and medication use, including antihypertensive, lipid-lowering and antidiabetic medication. However, results were often contradictory and inconclusive. Our objective was to study the associations established previously in more detail by sub-classifying medication groups, and investigate the potential mediating role of vitamin B12 and folate status. Materials and Methods Baseline data from the B-PROOF (B-vitamins for the PRevention Of Osteoporotic Fractures) study were used. We included 2,912 participants aged =65 years, with homocysteine levels of 12–50 µmol/L and creatinine levels =150 µmol/L, for whom self-reported medication data were available. We used multivariable linear regression models and analysis of covariance to assess the association between medication use and plasma homocysteine levels, and the potential mediation by serum vitamin B12 and folate. Results The mean age was 74 years (standard deviation, 6.5), 50 {\%} were women, and median homocysteine levels were 14 µmol/L [interquartile range, 13–17 µmol/L]. Higher mean homocysteine levels were observed in users vs. non-users for diuretics (15.2 vs. 14.9, p = 0.043), high-ceiling sulphonamide diuretics (16.0 vs. 14.9, p <0.001), medication acting via the renin-angiotensin system (15.2 vs. 14.9, p = 0.029) and metformin (15.6 vs. 15.1, p = 0.006). Non-selective {\ss}-blocker use was associated with lower mean homocysteine levels (14.4 vs. 15.0, p = 0.019). Only this association was mediated by an underlying association with vitamin B12 and folate levels. Conclusion The associations between homocysteine levels and medication use appear to be fairly modest. Our results suggest that medication use is unlikely to contribute to clinically relevant changes in plasma homocysteine levels.",
keywords = "type-2 diabetes-mellitus, plasma homocysteine, folic-acid, cardiovascular risk, parkinsons-disease, essential-hypertension, serum concentrations, c677t polymorphism, pharmacy records, controlled-trial",
author = "A.C. Ham and A.W. Enneman and {van Dijk}, S.C. and {van Wijngaarden}, J.P. and {van der Zwaluw}, N.L. and E.M. Brouwer and R.A.M. Dhonukshe-Rutten and {de Groot}, C.P.G.M. and R.F. Witkamp",
year = "2014",
doi = "10.1007/s40266-014-0192-2",
language = "English",
volume = "31",
pages = "611--621",
journal = "Drugs & Aging",
issn = "1170-229X",
publisher = "Springer Verlag",
number = "8",

}

Associations between medication use and homocysteine levels in an older population, and potential mediation by vitamin B12 and folate: data from the B-PROOF study. / Ham, A.C.; Enneman, A.W.; van Dijk, S.C.; van Wijngaarden, J.P.; van der Zwaluw, N.L.; Brouwer, E.M.; Dhonukshe-Rutten, R.A.M.; de Groot, C.P.G.M.; Witkamp, R.F.

In: Drugs & Aging, Vol. 31, No. 8, 2014, p. 611-621.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Associations between medication use and homocysteine levels in an older population, and potential mediation by vitamin B12 and folate: data from the B-PROOF study

AU - Ham, A.C.

AU - Enneman, A.W.

AU - van Dijk, S.C.

AU - van Wijngaarden, J.P.

AU - van der Zwaluw, N.L.

AU - Brouwer, E.M.

AU - Dhonukshe-Rutten, R.A.M.

AU - de Groot, C.P.G.M.

AU - Witkamp, R.F.

PY - 2014

Y1 - 2014

N2 - Background Elevated homocysteine levels are a risk indicator for cardiovascular disease, fractures and cognitive decline. Previous studies indicated associations between homocysteine levels and medication use, including antihypertensive, lipid-lowering and antidiabetic medication. However, results were often contradictory and inconclusive. Our objective was to study the associations established previously in more detail by sub-classifying medication groups, and investigate the potential mediating role of vitamin B12 and folate status. Materials and Methods Baseline data from the B-PROOF (B-vitamins for the PRevention Of Osteoporotic Fractures) study were used. We included 2,912 participants aged =65 years, with homocysteine levels of 12–50 µmol/L and creatinine levels =150 µmol/L, for whom self-reported medication data were available. We used multivariable linear regression models and analysis of covariance to assess the association between medication use and plasma homocysteine levels, and the potential mediation by serum vitamin B12 and folate. Results The mean age was 74 years (standard deviation, 6.5), 50 % were women, and median homocysteine levels were 14 µmol/L [interquartile range, 13–17 µmol/L]. Higher mean homocysteine levels were observed in users vs. non-users for diuretics (15.2 vs. 14.9, p = 0.043), high-ceiling sulphonamide diuretics (16.0 vs. 14.9, p <0.001), medication acting via the renin-angiotensin system (15.2 vs. 14.9, p = 0.029) and metformin (15.6 vs. 15.1, p = 0.006). Non-selective ß-blocker use was associated with lower mean homocysteine levels (14.4 vs. 15.0, p = 0.019). Only this association was mediated by an underlying association with vitamin B12 and folate levels. Conclusion The associations between homocysteine levels and medication use appear to be fairly modest. Our results suggest that medication use is unlikely to contribute to clinically relevant changes in plasma homocysteine levels.

AB - Background Elevated homocysteine levels are a risk indicator for cardiovascular disease, fractures and cognitive decline. Previous studies indicated associations between homocysteine levels and medication use, including antihypertensive, lipid-lowering and antidiabetic medication. However, results were often contradictory and inconclusive. Our objective was to study the associations established previously in more detail by sub-classifying medication groups, and investigate the potential mediating role of vitamin B12 and folate status. Materials and Methods Baseline data from the B-PROOF (B-vitamins for the PRevention Of Osteoporotic Fractures) study were used. We included 2,912 participants aged =65 years, with homocysteine levels of 12–50 µmol/L and creatinine levels =150 µmol/L, for whom self-reported medication data were available. We used multivariable linear regression models and analysis of covariance to assess the association between medication use and plasma homocysteine levels, and the potential mediation by serum vitamin B12 and folate. Results The mean age was 74 years (standard deviation, 6.5), 50 % were women, and median homocysteine levels were 14 µmol/L [interquartile range, 13–17 µmol/L]. Higher mean homocysteine levels were observed in users vs. non-users for diuretics (15.2 vs. 14.9, p = 0.043), high-ceiling sulphonamide diuretics (16.0 vs. 14.9, p <0.001), medication acting via the renin-angiotensin system (15.2 vs. 14.9, p = 0.029) and metformin (15.6 vs. 15.1, p = 0.006). Non-selective ß-blocker use was associated with lower mean homocysteine levels (14.4 vs. 15.0, p = 0.019). Only this association was mediated by an underlying association with vitamin B12 and folate levels. Conclusion The associations between homocysteine levels and medication use appear to be fairly modest. Our results suggest that medication use is unlikely to contribute to clinically relevant changes in plasma homocysteine levels.

KW - type-2 diabetes-mellitus

KW - plasma homocysteine

KW - folic-acid

KW - cardiovascular risk

KW - parkinsons-disease

KW - essential-hypertension

KW - serum concentrations

KW - c677t polymorphism

KW - pharmacy records

KW - controlled-trial

U2 - 10.1007/s40266-014-0192-2

DO - 10.1007/s40266-014-0192-2

M3 - Article

VL - 31

SP - 611

EP - 621

JO - Drugs & Aging

JF - Drugs & Aging

SN - 1170-229X

IS - 8

ER -