Role of cardiovascular risk factors on the hemodynamic changes of coronary microvascular function

Background

Globally, 112 million people are affected by angina pectoris, with half showing non-obstructive coronary artery disease linked to coronary microvascular dysfunction (CMD). CMD increases the risk of cardiovascular events, poorer outcomes and hospitalization. This research aims to understand the impact of cardiovascular risk factors on coronary microcirculation to develop preventative strategies and effective risk management.

Methods

Patients experiencing recurrent angina (CCS II-IV) without relevant epicardial stenosis were enrolled in a monocenter, prospective registry (MICRO).  Epicardial and microvascular responses (pressure, resistance and flow) were assessed using gold standard diagnostic methods at rest, during adenosine and acetylcholine testing using a pressure wire and the bolus thermodilution technique.

Results

We analyzed the influence of risk factors on coronary microcirculation in patients with angina. Older patients (>65 years) exhibited a higher Index of Microvascular Resistance (IMR) (21±15 vs. 17±12; p=0.012), lower Coronary Flow Reserve (CFR) (3.8±1.9 vs. 4.4±2.2; p=0.033) and Microvascular Resistance Reserve (MRR) (4.4±2.2 vs. 5.2±2.7; p=0.018). Linear regression showed an inverse relationship between age and both CFR (β=-0.7; p=0.026) and MRR (β=-0.7; p=0.009). Sex differences indicated that women had higher resting (2.1±1.4 vs. 1.5±0.9; p<0.001) and hyperemic flow (7.3±4.9 vs. 6.0±3.6; p=0.017), lower resting MR (676±38 vs. 78±38; p=0.024). CMD was more prevalent in women than men (65% vs. 51%; p=0.025).

In a subgroup analyses patients with normal BMI (<25 kg/m²) had a lower Ach-MRR (2.4±1.5 vs. 3.0±2.2; p=0.020) compared to overweight patients (BMI 25-30 kg/m²).  Diabetic patients displayed higher resting flow (2.2±1.3 vs. 1.7±1.2; p=0.017), lower resting MR (55±29 vs. 76±39; p=0.001) and Ach-IMR (27±19 vs. 38±28; p=0.023). A stratified analysis of chronic kidney disease according to eGFR (ml/min/1.73 m²) showed, that a reduced kidney function was associated with a reduced CFR (3.5±1.7 (eGFR <30) vs. 4.3±2.2 (eGFR 30-60); p=0.042). Heart failure patients exhibited a lower Adenosine-CFR (3.0±1.5 vs. 4.3±2.2; p<0.001), Adenosine-MRR (3.4±1.9 vs. 5.1±2.6; p<0.001), Ach-CFR (2.0±0.9 vs. 2.5±1.6; p=0.008), Ach-MRR (2.1±1.2 vs. 2.9±2.0; p=0.002) and higher Adenosine MR (26±20 vs. 18±11; p=0.015). In the overall population, 23% of the patients had an IMR>25, this proportion was significantly higher in the subgroup of heart failure (14 [39%] vs. 55 [23%]; p=0.017).

Smokers displayed higher Ach-MRR (3.6±2.6 vs. 2.6±1.7; p=0.044) than non-smokers, with variations in Ach-MR and CFR between smoking intensities. Comparing ex-smokers (<10 years) to smokers (10-20 cigarettes/day) revealed that smokers had significantly lower Ach-MR, Ach-CFR and Ach-MRR. Smokers (>20 cigarettes/day) had lower resting and Adenosine-MR, lower Ach-MRR and Ach-CFR compared to both ex-smokers and smokers (10-20 cigarettes/day) (Table 1).

Conclusion (s)

Risk factors significantly influence coronary microcirculation, by altering flow and resistance. Aging, heart failure, chronic kidney dysfunction lower CFR and increase resistance, while smoking, diabetes and sex increase basal flow and lower resistance. These findings underscore the importance of preventative treatment and risk factor management, to alleviate CMD and ischemic myocardial changes. Acetylcholine testing proved to be a safe procedure with low rates of complications.