Reimagining the Value of Brachial-Ankle Pulse Wave Velocity as a Biomarker of Cardiovascular Disease Risk-A Call to Action on Behalf of VascAgeNet

Abstract

This review critiques the literature supporting clinical assessment and management of cardiovascular disease and cardiovascular disease risk stratification with brachial-ankle pulse wave velocity (baPWV). First, we outline what baPWV actually measures-arterial stiffness of both large central elastic arteries and medium-sized muscular peripheral arteries of the lower limb. Second, we argue that baPWV is not a surrogate for carotid-femoral pulse wave velocity. While both measures are dependent on the properties of the aorta, baPWV is also strongly dependent on the muscular arteries of the lower extremities. Increased lower-extremity arterial stiffness amplifies and hastens wave reflections at the level of the aorta, widens pulse pressure, increases afterload, and reduces coronary perfusion. Third, we used an established evaluation framework to identify the value of baPWV as an independent vascular biomarker. There is sufficient evidence to support (1) proof of concept; (2) prospective validation; (3) incremental value; and (4) clinical utility. However, there is limited or no evidence to support (5) clinical outcomes; (6) cost-effectiveness; (8) methodological consensus; or (9) reference values. Fourth, we address future research requirements. The majority of the evaluation criteria, (1) proof of concept, (2) prospective validation, (3) incremental value, (4) clinical utility and (9) reference values, can be supported using existing cohort datasets, whereas the (5) clinical outcomes and (6) cost-effectiveness criteria require prospective investigation. The (8) methodological consensus criteria will require an expert consensus statement. Finally, we finish this review by providing an example of a future clinical practice model.

Keywords: arterial stiffness; biomarkers; cardiovascular disease risk; pulse wave velocity; vascular aging.

Figure 1.

Comparison of wall composition and changes in pulse wave velocity with age between central and peripheral arterial regions. Brachial-ankle pulse wave velocity (baPWV; composite measure) summates the arterial properties between the descending aorta at the level of the brachial artery and the ankle, comprising of arteries or arterial regions (eg, the aorta) with different structural and mechanical characteristics. cfPWV indicates carotid-femoral pulse wave velocity (central); crPWV, carotid-radial pulse wave velocity; and faPWV, femoral-ankle pulse wave velocity (lower-limb). VSMC indicates vascular smooth muscle cell.

Figure 2.

Schematic for the measurement of brachial-ankle pulse wave velocity (baPWV). baPWV is estimated as the length between the sternal notch and the ankle (L_SA) minus the sternal notch to brachium (L_SB), as determined by body surface measurements or height-based formulas, divided by the time delay between brachial and ankle waveforms (∆T_BA). Note: solid line denotes effective path length.

Figure 3.

Example of a potential future clinical practice model in the form of a decision tree. In this example, traditional risk factors will be measured and used to stratify all-cause cardiovascular disease (CVD) risk. Subsequently, ankle brachial index (ABI) and systolic interarm blood pressure difference (IAD) are measured. Positive ABI and IAD (ie, unhealthy, ABI score <0.9 or >1.4 and IAD≥10 mm Hg) scores indicates peripheral arterial disease (PAD) and increased myocardial infarction (MI) and stroke risk. If the ABI and IAD scores are negative (ie, healthy, ABI: between 0.9 and 1.4; IAD<10 mm Hg), the additional information provided by brachial-ankle pulse wave velocity (baPWV) and pulse wave analysis (PWA) will be considered. A positive baPWV indicates increased risk for all-cause cardiovascular events, acute coronary syndrome (ACS), and target organ damage (TOD) risk. A positive PWA score may indicate increased afterload and increased heart failure (HF) risk. If both the baPWV and PWA scores are negative, the participant is sent home with a wearable device to collect ambulatory PWA and baPWV data, from which a composite CVD risk score is derived.