TY - JOUR
T1 - A genetic risk score for fasting plasma glucose is independently associatedwith arterial stiffness
T2 - A Mendelian randomization study
AU - Gottsäter, Mikael
AU - Hindy, George
AU - Orho-Melander, Marju
AU - Nilsson, Peter M.
AU - Melander, Olle
PY - 2018
Y1 - 2018
N2 - 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.
AB - 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.
KW - Aging
KW - Arterial stiffness
KW - Diabetes mellitus
KW - Epidemiology
KW - Hyperglycemia
KW - Mendelian randomization
UR - http://www.scopus.com/inward/record.url?scp=85050544074&partnerID=8YFLogxK
U2 - 10.1097/HJH.0000000000001646
DO - 10.1097/HJH.0000000000001646
M3 - Article
C2 - 29215398
AN - SCOPUS:85050544074
SN - 0263-6352
VL - 36
SP - 809
EP - 814
JO - Journal of Hypertension
JF - Journal of Hypertension
IS - 4
ER -