Peripheral Microvascular Function Reflects Coronary Vascular Function

Abstract

Objectives- Coronary endothelial dysfunction is a precursor of atherosclerosis and adverse outcomes. Whether endothelial dysfunction is a localized or generalized phenomenon in humans remains uncertain. We simultaneously measured femoral and coronary vascular function with the hypothesis that peripheral vascular endothelial function will be reflective of coronary endothelial function. Approach and Results- Eighty-five subjects underwent coronary angiography for evaluation of chest pain or abnormal stress tests. Endothelium-dependent and -independent vascular function were measured using intracoronary and intrafemoral infusions of acetylcholine and sodium nitroprusside, respectively. Coronary flow reserve was assessed using intracoronary adenosine infusion. Flow velocity was measured in each circulation using a Doppler wire (FloWire, EndoSonics). Coronary vascular resistance and femoral vascular resistance were calculated as mean arterial pressure (mm Hg)/coronary blood flow (mL/min) and mean arterial pressure (mm Hg)/femoral average peak velocity (cm/s), respectively. Mean age was 53±11 years, 37% were female, 44% had hypertension, 12% had diabetes mellitus, and 38% had obstructive coronary artery disease. There was a correlation between the change in femoral vascular resistance with acetylcholine and acetylcholine-mediated changes in both the coronary vascular resistance ( r=0.27; P=0.014) and in the epicardial coronary artery diameter ( r=-0.25; P=0.021), indicating that subjects with normal endothelial function in the femoral circulation had normal endothelial function in the coronary epicardial and microcirculation and vice versa. The coronary vasodilator response to adenosine also correlated with the femoral vasodilatation with acetylcholine ( r=0.4; P=0.0002). There was no correlation between the coronary and femoral responses to sodium nitroprusside. Conclusions- Endothelial functional changes in the peripheral and coronary circulations were modestly correlated. Thus, peripheral microvascular endothelial function reflects endothelium-dependent coronary epicardial and microvascular function and the coronary flow reserve. Visual Overview- An online visual overview is available for this article.

Keywords: acetylcholine; blood flow velocity; endothelium; nitroprusside; vascular resistance.

Figure 1:. Coronary angiograms, intracoronary Doppler tracing and hemodynamic measurements during the study protocol.

The Doppler Wire is positioned in the mid-left anterior descending coronary artery. Coronary artery diameter is measured 5 mm distal to the Doppler wire tip at rest (A) and after acetylcholine infusion (B). Acetylcholine infusion resulted in severe coronary vasoconstriction. (C) Intracoronary Doppler tracing and hemodynamic measurements of the subject during the study protocol. LAD: left anterior descending artery; Ach: acetylcholine; APV: average peak velocity.

Figure 2:. Relationship between coronary and femoral microvascular function in response to acetylcholine.

Relationship between the percent changes in (A) femoral blood flow velocity and coronary blood flow in response to acetylcholine infusions, (B) femoral vascular resistance and coronary vascular resistance in response to acetylcholine infusions.

Figure 3:. Relationship between coronary epicardial and femoral microvascular functions.

Relationship between the percent changes in (A) femoral vascular resistance and change in coronary diameter in response to acetylcholine infusion, (B) femoral vascular resistance and change in coronary diameter in response to sodium nitroprusside infusion. NS: not significant.

Figure 4:. Relationship between coronary flow reserve and femoral microvascular function.

Relationship between the percent changes in (A) femoral blood flow velocity and coronary blood flow in response to acetylcholine and adenosine infusions, respectively, (B) femoral vascular resistance and coronary vascular resistance in response to acetylcholine and adenosine infusions, respectively.