Left ventricular hypertrophy contributes to Myocardial Ischemia in Non-obstructive Coronary Artery Disease (the MicroCAD study)

Background: The underlying mechanisms causing myocardial ischemia in non-obstructive coronary artery disease (CAD) are still unclear. We explored whether left ventricular hypertrophy (LVH) was associated with myocardial ischemia in patients with stable angina and non-obstructive CAD. Methods: 132 patients (mean age 63 ± 8 years, 56% women) with stable angina and non-obstructive CAD diagnosed as 46.7 g/m2.7 in women and >49.2 g/m2.7 in men. Patients were grouped according to presence or absence of myocardial ischemia by myocardial contrast stress echocardiography. The number of LV segments with ischemia at peak stress was taken as a measure of the extent of myocardial ischemia. Results: Myocardial ischemia was found in 52% of patients, with on average 5 ± 3 ischemic LV segments per patient. The group with myocardial ischemia had higher prevalence of LVH (23 vs. 10%, p = 0.035), while age, sex and prevalence of hypertension did not differ between groups (all p > 0.05). In multivariable regression analyses, LVH was associated with presence of myocardial ischemia (odds ratio 3.27, 95% confidence interval [1.11–9.60], p = 0.031), and larger extent of myocardial ischemia (β = 0.22, p = 0.012), independent of confounders including age, hypertension, obesity, hypercholesterolemia, calcium score and segment involvement score by CCTA. Conclusions: LVH was independently associated with both presence and extent of myocardial ischemia in patients with stable angina and non-obstructive CAD by CCTA. These results suggest LVH as an independent contributor to myocardial ischemia in non-obstructive CAD.publishedVersio

Impact of aortic stiffness on myocardial ischaemia in non-obstructive coronary artery disease

Objective: High aortic stiffness may reduce myocardial perfusion pressure and contribute to development of myocardial ischaemia. Whether high aortic stiffness is associated with myocardial ischaemia in patients with stable angina and non-obstructive coronary artery disease (CAD) is less explored. Methods: Aortic stiffness was assessed as carotid-femoral pulse wave velocity (PWV) by applanation tonometry in 125 patients (62±8 years, 58% women) with stable angina and non-obstructive CAD participating in the Myocardial Ischemia in Non-obstructive CAD project. PWV in the highest tertile (>8.7 m/s) was taken as higher aortic stiffness. Stress-induced myocardial ischaemia was detected as delayed myocardial contrast replenishment during stress echocardiography, and the number of left ventricular (LV) segments with delayed contrast replenishment as the extent of ischaemia. Results: Patients with higher aortic stiffness were older with higher LV mass index and lower prevalence of obesity (all p<0.05), while angina symptoms, sex, prevalence of hypertension, diabetes, smoking or LV ejection fraction did not differ between groups. Stress-induced myocardial ischaemia was more common (73% vs 42%, p=0.001) and the extent of ischaemia was larger (4±3 vs 2±3 LV segments, p=0.005) in patients with higher aortic stiffness. In multivariable logistic regression analysis, higher aortic stiffness was associated with stress-induced myocardial ischaemia independent of other known covariables (OR 4.74 (95% CI 1.51 to 14.93), p=0.008). Conclusions: In patients with stable angina and non-obstructive CAD, higher aortic stiffness was associated with stress-induced myocardial ischaemia. Consequently, assessment of aortic stiffness may add to the diagnostic evaluation in patients with non-obstructive CAD.publishedVersio

Relationship between hypertension and nonobstructive coronary artery disease in chronic coronary syndrome (the NORIC registry)

Background The burden of non-obstructive coronary artery disease (CAD) in the society is high, and there is currently limited evidence-based recommendation for risk stratification and treatment. Previous studies have demonstrated an association between increasing extent of non-obstructive CAD and cardiovascular events. Whether hypertension, a modifiable cardiovascular risk factor, is associated with extensive non-obstructive CAD in patients with symptomatic chronic coronary syndrome (CCS) remains unclear. Methods We included 1138 patients (mean age 62±11 years, 48% women) with symptomatic CCS and non-obstructive CAD (1–49% lumen diameter reduction) by coronary computed tomography angiography (CCTA) from the Norwegian Registry for Invasive Cardiology (NORIC). The extent of non-obstructive CAD was assessed as coronary artery segment involvement score (SIS), and extensive non-obstructive CAD was adjudicated when SIS >4. Hypertension was defined as known hypertension or use of antihypertensive medication. Results Hypertension was found in 45% of patients. Hypertensive patients were older, with a higher SIS, calcium score, and prevalence of comorbidities and statin therapy compared to the normotensive (all p<0.05). There was no difference in the prevalence of hypertension between sexes. Univariable analysis revealed a significant association between hypertension and non-obstructive CAD. In multivariable analysis, hypertension remained associated with extensive non-obstructive CAD, independent of sex, age, smoking, diabetes, statin treatment, obesity and calcium score (OR 1.85, 95% CI [1.22–2.80], p = 0.004). Conclusion In symptomatic CCS, hypertension was associated with extensive non-obstructive CAD by CCTA. Whether hypertension may be a new treatment target in symptomatic non-obstructive CAD needs to be explored in future studies.publishedVersio

Myocardial ischemia in non-obstructive coronary artery disease : Associations with coronary artery disease morphology and left ventricular hypertrophy

Background: The underlying mechanisms causing myocardial ischemia in non-obstructive coronary artery disease (CAD) are incompletely understood. We tested whether the total coronary artery plaque burden, coronary tortuosity and left ventricular hypertrophy were independently associated with myocardial ischemia. Material and methods: Study 1 included 108 patients with non-ST-elevation myocardial infarction (NSTEMI), and coronary artery plaque burden and tortuosity were assessed by quantitative invasive coronary angiography. Study 2 included 132 symptomatic patients with non-obstructive CAD by coronary computed tomography angiography (CCTA), and left ventricular hypertrophy was determined by echocardiography. In study 3, coronary artery plaque burden was assessed by quantitative CCTA in 125 symptomatic patients with non-obstructive CAD. Myocardial ischemia was determined using myocardial contrast echocardiography at rest in study 1 and during pharmacological stress in study 2 and 3. Results: In study 1, coronary artery plaque burden was associated with severe myocardial ischemia independent of angiographic stenosis severity and cardiovascular risk factors. No association was found between coronary artery tortuosity and ischemia. In study 2, left ventricular hypertrophy was associated with myocardial ischemia, independent of cardiovascular risk factors and coronary calcium score. In study 3, coronary artery plaque burden estimated by CCTA was associated with myocardial ischemia, independent of left ventricular mass index, coronary calcium score and cardiovascular risk factors. Conclusion: Coronary artery plaque burden was independently associated with myocardial ischemia both in NSTEMI and in symptomatic patients with non-obstructive CAD. Left ventricular hypertrophy was independently associated with myocardial ischemia in patients with non-obstructive CAD. These results suggest that the coronary plaque burden and left ventricular hypertrophy may contribute to myocardial ischemia independent of CAD severity

Myocardial ischemia in non-obstructive coronary artery disease : Associations with coronary artery disease morphology and left ventricular hypertrophy

Background: The underlying mechanisms causing myocardial ischemia in non-obstructive coronary artery disease (CAD) are incompletely understood. We tested whether the total coronary artery plaque burden, coronary tortuosity and left ventricular hypertrophy were independently associated with myocardial ischemia. Material and methods: Study 1 included 108 patients with non-ST-elevation myocardial infarction (NSTEMI), and coronary artery plaque burden and tortuosity were assessed by quantitative invasive coronary angiography. Study 2 included 132 symptomatic patients with non-obstructive CAD by coronary computed tomography angiography (CCTA), and left ventricular hypertrophy was determined by echocardiography. In study 3, coronary artery plaque burden was assessed by quantitative CCTA in 125 symptomatic patients with non-obstructive CAD. Myocardial ischemia was determined using myocardial contrast echocardiography at rest in study 1 and during pharmacological stress in study 2 and 3. Results: In study 1, coronary artery plaque burden was associated with severe myocardial ischemia independent of angiographic stenosis severity and cardiovascular risk factors. No association was found between coronary artery tortuosity and ischemia. In study 2, left ventricular hypertrophy was associated with myocardial ischemia, independent of cardiovascular risk factors and coronary calcium score. In study 3, coronary artery plaque burden estimated by CCTA was associated with myocardial ischemia, independent of left ventricular mass index, coronary calcium score and cardiovascular risk factors. Conclusion: Coronary artery plaque burden was independently associated with myocardial ischemia both in NSTEMI and in symptomatic patients with non-obstructive CAD. Left ventricular hypertrophy was independently associated with myocardial ischemia in patients with non-obstructive CAD. These results suggest that the coronary plaque burden and left ventricular hypertrophy may contribute to myocardial ischemia independent of CAD severity

Global coronary artery plaque area is associated with myocardial hypoperfusion in women with non-ST elevation myocardial infarction

Background: Women with non-ST elevation myocardial infarction (NSTEMI) have similar extent of myocardial ischemia but less obstructive coronary artery disease (CAD) than their male counterparts. We tested the impact of global coronary artery plaque area and artery tortuosity on myocardial perfusion in NSTEMI patients. Methods: Coronary artery plaque area was determined by quantitative angiography in 108 patients (32% women) with NSTEMI. Myocardial perfusion was assessed by contrast echocardiography in the 17 individual left ventricular segments. Artery tortuosity was defined as ‡ 3 curves > 45 in a main coronary artery. Results: Age, prevalence of hypertension, and diabetes did not differ between sexes (all nonsignificant). Women had lower prevalence of ‡ 50% coronary artery stenosis (74% vs. 91%, p 0.07). In multivariate analysis, larger coronary artery plaque area was associated with a 35% higher risk for having severe myocardial hypoperfusion (odds ratio 1.35 [95% confidence interval 1.01–1.80], p < 0.05) in the total study population, while no association between artery tortuosity and myocardial ischemia was found. Similar results were obtained in separate analysis among women and men. Conclusion: In women and men with NSTEMI, the global coronary artery plaque area was an important determinant of the severity of myocardial hypoperfusion at rest independent of presence of significant coronary stenoses. These findings may expand current understanding of NSTEMI in patients with nonobstructive CAD

Left ventricular hypertrophy contributes to Myocardial Ischemia in Non-obstructive Coronary Artery Disease (the MicroCAD study)

Background: The underlying mechanisms causing myocardial ischemia in non-obstructive coronary artery disease (CAD) are still unclear. We explored whether left ventricular hypertrophy (LVH) was associated with myocardial ischemia in patients with stable angina and non-obstructive CAD. Methods: 132 patients (mean age 63 ± 8 years, 56% women) with stable angina and non-obstructive CAD diagnosed as 46.7 g/m2.7 in women and >49.2 g/m2.7 in men. Patients were grouped according to presence or absence of myocardial ischemia by myocardial contrast stress echocardiography. The number of LV segments with ischemia at peak stress was taken as a measure of the extent of myocardial ischemia. Results: Myocardial ischemia was found in 52% of patients, with on average 5 ± 3 ischemic LV segments per patient. The group with myocardial ischemia had higher prevalence of LVH (23 vs. 10%, p = 0.035), while age, sex and prevalence of hypertension did not differ between groups (all p > 0.05). In multivariable regression analyses, LVH was associated with presence of myocardial ischemia (odds ratio 3.27, 95% confidence interval [1.11–9.60], p = 0.031), and larger extent of myocardial ischemia (β = 0.22, p = 0.012), independent of confounders including age, hypertension, obesity, hypercholesterolemia, calcium score and segment involvement score by CCTA. Conclusions: LVH was independently associated with both presence and extent of myocardial ischemia in patients with stable angina and non-obstructive CAD by CCTA. These results suggest LVH as an independent contributor to myocardial ischemia in non-obstructive CAD

Total coronary atherosclerotic plaque burden is associated with myocardial ischemia in non-obstructive coronary artery disease

Aim Whether the total coronary atherosclerotic plaque burden is independently associated with myocardial ischemia in non-obstructive coronary artery disease (CAD) is not well established. We aimed to test the association of total plaque burden quantified by coronary computed tomography angiography (CCTA) with myocardial ischemia in patients with chronic coronary syndrome and non-obstructive CAD. Methods We included 125 patients (age 62 ± 9 years, 58% women) with chronic coronary syndrome and non-obstructive CAD (stenosis 1.10. Results Patients with myocardial ischemia (n = 66) had higher total plaque burden (847 ± 245 mm3 vs. 758 ± 251 mm3, p = 0.049) and higher left ventricular (LV) mass index (42.1 ± 9.9 g/m2.7 vs. 37.3 ± 8.0 g/m2.7, p = 0.004), while age, sex, prevalence of hypertension, diabetes, calcium score and positive remodelling did not differ between the groups (all p > 0.05). In multivariable regression analysis, total plaque burden remained associated with presence of myocardial ischemia (OR 1.02, 95% CI 1.00–1.04, p = 0.045) independent of age, sex, hypertension, diabetes, LV mass index, coronary calcium score and positive remodelling. Conclusion Total coronary artery plaque burden by CCTA was independently associated with myocardial ischemia in patients with non-obstructive CAD. Whether plaque quantification is useful for clinical management of patients with non-obstructive CAD should be tested in prospective studies