Genetic Association of Arterial Stiffness Index with Blood Pressure and Coronary Artery Disease

Abstract Background Arterial stiffness index (ASI) is independently associated with blood pressure and coronary artery disease (CAD) in epidemiologic studies. However, it is unknown whether these associations represent causal relationships.Objectives Here, we assess whether genetic predisposition to increased ASI is associated with elevated blood pressure and CAD risk.Methods Genome-wide association analysis (GWAS) of finger photoplethysmography-derived ASI was performed in 131,686 participants from the UK Biobank. Across UK Biobank participants not in the ASI GWAS, a 6-variant ASI polygenic risk score was calculated. The ASI polygenic score was associated with systolic and diastolic blood pressures (SBP, DBP, N=208,897), and with incident CAD over 10 years follow-up (N=223,061; 7,534 cases). The lack of CAD association observed was replicated among 184,305 participants (60,810 cases) from the Coronary Artery Disease Genetics Consortium (CARDIOGRAMplusC4D).Results We replicated prior reports of the epidemiologic association of ASI with SBP (Beta 0.55mmHg, [95% CI, 0.45–0.65],P=5.77×10−24), DBP (Beta 1.05mmHg, [95% CI, 0.99–1.11],P=7.27×10−272), and incident CAD (HR 1.08 [95% CI, 1.04–1.11],P=1.5×10−6) in multivariable models. While each SD increase in genetic predisposition to elevated ASI was highly associated with SBP (Beta 4.63 mmHg [95% CI, 2.1–7.2];P=3.37×10−4), and DBP (Beta 2.61 mmHg [95% CI, 1.2–4.0];P=2.85×10−4), no association was observed with incident CAD in UK Biobank (HR 1.12 [95% CI, 0.55–2.3];P=0.75), or with prevalent CAD in CARDIOGRAMplusC4D (OR 0.56 [95% CI, 0.26–1.24];P=0.15).Conclusions A genetic predisposition to higher ASI was associated with elevated blood pressure but not with increased risk of developing CAD.Condensed Abstract Arterial stiffness index (ASI) is proposed by some as a surrogate of blood pressure and coronary artery disease (CAD) risk based on epidemiologic analyses. We tested whether genetic predisposition to increased ASI is associated with elevated blood pressure and CAD risk to assess whether these represent causal relationships. We find that a genetic predisposition to higher ASI is associated with elevated systolic (Beta 4.63 mmHg [95% CI, 2.1–7.2]) and diastolic blood pressures (Beta 2.61 mmHg [95% CI, 1.2–4.0]) in the UK Biobank, but not associated with incident CAD in the UK Biobank (P=0.75) or with prevalent CAD in CARDIOGRAMplusC4D (P=0.15). These data support a causal relationship of ASI with blood pressure but do not support the notion that ASI is a suitable surrogate for CAD risk..

Medienart:	Preprint

Erscheinungsjahr:	2022
Erschienen:	2022

Enthalten in:	bioRxiv.org - (2022) vom: 04. Sept. Zur Gesamtaufnahme - year:2022

Sprache:	Englisch

Beteiligte Personen:	Zekavat, Seyedeh M. [VerfasserIn] Haas, Mary [VerfasserIn] Aragam, Krishna [VerfasserIn] Emdin, Connor [VerfasserIn] Khera, Amit V. [VerfasserIn] Klarin, Derek [VerfasserIn] Zhao, Hongyu [VerfasserIn] Natarajan, Pradeep [VerfasserIn]

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Themen:	570 Biology

doi:	10.1101/453878

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PPN (Katalog-ID):	XBI000379735