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A genetic risk score for fasting plasma glucose is independently associatedwith arterial stiffness : A Mendelian randomization study

Gottsäter, Mikael LU ; Hindy, George LU ; Orho-Melander, Marju LU ; Nilsson, Peter M. LU and Melander, Olle LU (2018) In Journal of Hypertension 36(4). p.809-814
Abstract

Background: Arterial stiffness is known to be associated with a number of clinical conditions including hypertension, diabetes and dyslipidemia, and may predict cardiovascular events and mortality. However, causal links are hard to establish. Results from genome-wide association studies have identified only a few single nucleotide polymorphisms associated with arterial stiffness, the results have been inconsistent between studies and overlap with other clinical conditions is lacking. Our aim was to investigate a potential shared set of risk single nucleotide polymorphisms between relevant cardiometabolic traits and arterial stiffness. Method: The study population consisted of 2853 individuals (mean age 72 years, 40% men) from the... (More)

Background: Arterial stiffness is known to be associated with a number of clinical conditions including hypertension, diabetes and dyslipidemia, and may predict cardiovascular events and mortality. However, causal links are hard to establish. Results from genome-wide association studies have identified only a few single nucleotide polymorphisms associated with arterial stiffness, the results have been inconsistent between studies and overlap with other clinical conditions is lacking. Our aim was to investigate a potential shared set of risk single nucleotide polymorphisms between relevant cardiometabolic traits and arterial stiffness. Method: The study population consisted of 2853 individuals (mean age 72 years, 40% men) from the population-based Malmö Diet and Cancer study, Sweden. Carotid-femoral pulse wave velocity, a marker of arterial stiffness, was measured with Sphygmocor. Mendelian randomization analyses were performed using the twostage least square regression and multivariate inversevariance weighted methods. Results: There were positive associations between arterial stiffness and genetic risk scores for type 2 diabetes (β=0.03, P=0.04) and fasting plasma glucose (β=0.03, P=0.03), but not for systolic blood pressure, body mass index, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglycerides. Multivariate inversevariance weighted methods confirmed the significant positive association for fasting plasma glucose β coefficients (P=0.006), but not for type 2 diabetes β coefficients (P=0.88). Conclusion: Genetically elevated fasting plasma glucose, but not genetically elevated risk of type 2 diabetes, was associated with arterial stiffness suggesting a causal stiffening effect of glycemia on the arterial wall, independently of type 2 diabetes.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Aging, Arterial stiffness, Diabetes mellitus, Epidemiology, Hyperglycemia, Mendelian randomization
in
Journal of Hypertension
volume
36
issue
4
pages
6 pages
publisher
Lippincott Williams & Wilkins
external identifiers
  • scopus:85050544074
  • pmid:29215398
ISSN
0263-6352
DOI
10.1097/HJH.0000000000001646
language
English
LU publication?
yes
id
f777cf21-99cd-4689-bfa3-d7ef3f9e6b1a
date added to LUP
2019-10-08 10:26:40
date last changed
2019-12-10 08:15:50
@article{f777cf21-99cd-4689-bfa3-d7ef3f9e6b1a,
  abstract     = {<p>Background: Arterial stiffness is known to be associated with a number of clinical conditions including hypertension, diabetes and dyslipidemia, and may predict cardiovascular events and mortality. However, causal links are hard to establish. Results from genome-wide association studies have identified only a few single nucleotide polymorphisms associated with arterial stiffness, the results have been inconsistent between studies and overlap with other clinical conditions is lacking. Our aim was to investigate a potential shared set of risk single nucleotide polymorphisms between relevant cardiometabolic traits and arterial stiffness. Method: The study population consisted of 2853 individuals (mean age 72 years, 40% men) from the population-based Malmö Diet and Cancer study, Sweden. Carotid-femoral pulse wave velocity, a marker of arterial stiffness, was measured with Sphygmocor. Mendelian randomization analyses were performed using the twostage least square regression and multivariate inversevariance weighted methods. Results: There were positive associations between arterial stiffness and genetic risk scores for type 2 diabetes (β=0.03, P=0.04) and fasting plasma glucose (β=0.03, P=0.03), but not for systolic blood pressure, body mass index, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglycerides. Multivariate inversevariance weighted methods confirmed the significant positive association for fasting plasma glucose β coefficients (P=0.006), but not for type 2 diabetes β coefficients (P=0.88). Conclusion: Genetically elevated fasting plasma glucose, but not genetically elevated risk of type 2 diabetes, was associated with arterial stiffness suggesting a causal stiffening effect of glycemia on the arterial wall, independently of type 2 diabetes.</p>},
  author       = {Gottsäter, Mikael and Hindy, George and Orho-Melander, Marju and Nilsson, Peter M. and Melander, Olle},
  issn         = {0263-6352},
  language     = {eng},
  number       = {4},
  pages        = {809--814},
  publisher    = {Lippincott Williams & Wilkins},
  series       = {Journal of Hypertension},
  title        = {A genetic risk score for fasting plasma glucose is independently associatedwith arterial stiffness : A Mendelian randomization study},
  url          = {http://dx.doi.org/10.1097/HJH.0000000000001646},
  doi          = {10.1097/HJH.0000000000001646},
  volume       = {36},
  year         = {2018},
}