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

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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

VL - 36

SP - 809

EP - 814

JO - Journal of Hypertension

JF - Journal of Hypertension

SN - 1473-5598

IS - 4

ER -