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. 2022 Sep 2;131(6):545-554.
doi: 10.1161/CIRCRESAHA.122.320796. Epub 2022 Aug 10.

Arterial Stiffness and Diabetes Risk in Framingham Heart Study and UK Biobank

Jordana B Cohen  1   2 , Gary F Mitchell  3 , Dipender Gill  4 , Stephen Burgess  5   6 , Mahboob Rahman  7 , Thomas C Hanff  8 , Vasan S Ramachandran  9   10   11 , Karen M Mutalik  11 , Raymond R Townsend  1 , Julio A Chirinos  12
Affiliations

Arterial Stiffness and Diabetes Risk in Framingham Heart Study and UK Biobank

Jordana B Cohen et al. Circ Res. .

Abstract

Background: Microvascular damage from large artery stiffness (LAS) in pancreatic, hepatic, and skeletal muscles may affect glucose homeostasis. Our goal was to evaluate the association between LAS and the risk of type 2 diabetes using prospectively collected, carefully phenotyped measurements of LAS as well as Mendelian randomization analyses.

Methods: Carotid-femoral pulse wave velocity (CF-PWV) and brachial and central pulse pressure were measured in 5676 participants of the FHS (Framingham Heart Study) without diabetes. We used Cox proportional hazards regression to evaluate the association of CF-PWV and pulse pressure with incident diabetes. We subsequently performed 2-sample Mendelian randomization analyses evaluating the associations of genetically predicted brachial pulse pressure with type 2 diabetes in the UKBB (United Kingdom Biobank).

Results: In FHS, individuals with higher CF-PWV were older, more often male, and had higher body mass index and mean arterial pressure compared to those with lower CF-PWV. After a median follow-up of 7 years, CF-PWV and central pulse pressure were associated with an increased risk of new-onset diabetes (per SD increase, multivariable-adjusted CF-PWV hazard ratio, 1.36 [95% CI, 1.03-1.76]; P=0.030; central pulse pressure multivariable-adjusted CF-PWV hazard ratio, 1.26 [95% CI, 1.08-1.48]; P=0.004). In United Kingdom Biobank, genetically predicted brachial pulse pressure was associated with type 2 diabetes, independent of mean arterial pressure (adjusted odds ratio, 1.16 [95% CI, 1.00-1.35]; P=0.049).

Conclusions: Using prospective cohort data coupled with Mendelian randomization analyses, we found evidence supporting that greater LAS is associated with increased risk of developing diabetes. LAS may play an important role in glucose homeostasis and may serve as a useful marker of future diabetes risk.

Keywords: blood pressure; carotid-femoral pulse wave velocity; hemodynamics; human genetics; vascular stiffness.

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Conflict of interest statement

DISCLOSURES

JAC has recently consulted for Bayer, Sanifit, Fukuda-Denshi, Bristol-Myers Squibb, JNJ, Edwards Life Sciences, Merck, NGM Biopharmaceuticals and the Galway-Mayo Institute of Technology. He received University of Pennsylvania research grants from National Institutes of Health, Fukuda-Denshi, Bristol-Myers Squibb, Microsoft and Abbott. He is named as inventor in a University of Pennsylvania patent for the use of inorganic nitrates/nitrites for the treatment of Heart Failure and Preserved Ejection Fraction and for the use of biomarkers in heart failure with preserved ejection fraction. He has received payments for editorial roles from the American Heart Association, the American College of Cardiology and Wiley. He has received research device loans from Atcor Medical, Fukuda-Denshi, Unex, Uscom, NDD Medical Technologies, Microsoft and MicroVision Medical. GFM is the owner of Cardiovascular Engineering, Inc., a small business that designs and develops devices that are used to measure arterial stiffness and has received consulting fees or grants from Novartis, Merck, Bayer and Servier. DG is employed part-time by Novo Nordisk. The remaining authors have nothing to disclose.

Figures

Figure 1.
Figure 1.. Distribution of CF-PWV in the FHS
Violin plots depict the frequency distribution (outer histogram), median (white circle), interquartile range (box), and 1.5 multiple of the interquartile range (solid lines) of CF-PWV.
Figure 2.
Figure 2.. Association of CF-PWV and new-onset DM in the FHS
Estimates represent the hazard ratio (solid lines) and 95% confidence intervals of the hazard ratios (dashes) at each value of CF-PWV using Cox regression.
Figure 3.
Figure 3.. Associations of genetically-predicted blood pressure measures and type 2 DM risk in univariable and multivariable Mendelian randomization analyses
Estimates (95% confidence intervals [CI]) represent the odds ratio for disease per 5 mmHg increase in genetically-predicted levels of the blood pressure trait.
See this image and copyright information in PMC

Comment in

References

    1. Chirinos JA, Segers P, Hughes T, Townsend R. Large-Artery Stiffness in Health and Disease: JACC State-of-the-Art Review. Journal of the American College of Cardiology. 2019;74:1237–1263. doi: 10.1016/j.jacc.2019.07.012 - DOI - PMC - PubMed
    1. Townsend RR, Wilkinson IB, Schiffrin EL, Avolio AP, Chirinos JA, Cockcroft JR, Heffernan KS, Lakatta EG, McEniery CM, Mitchell GF, et al. Recommendations for Improving and Standardizing Vascular Research on Arterial Stiffness: A Scientific Statement From the American Heart Association. Hypertension. 2015;66:698–722. doi: 10.1161/HYP.0000000000000033 - DOI - PMC - PubMed
    1. Townsend RR, Anderson AH, Chirinos JA, Feldman HI, Grunwald JE, Nessel L, Roy J, Weir MR, Wright JT, Bansal N Jr., et al. Association of Pulse Wave Velocity With Chronic Kidney Disease Progression and Mortality: Findings From the CRIC Study (Chronic Renal Insufficiency Cohort). Hypertension. 2018;71:1101–1107. doi: 10.1161/HYPERTENSIONAHA.117.10648 - DOI - PMC - PubMed
    1. O’Rourke MF, Safar ME. Relationship between aortic stiffening and microvascular disease in brain and kidney: cause and logic of therapy. Hypertension. 2005;46:200–204. doi: 10.1161/01.HYP.0000168052.00426.65 - DOI - PubMed
    1. Nichols WW ORM, Vlachopoulos C. McDonald’s Blood Flow in Arteries: Theoretical, Experimental and Clinical Principles, 6th Edition. Hodder Arnold. 2011.

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