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

Altered mitochondrial metabolism in the insulin-resistant heart.

Obesity-induced insulin resistance and type 2 diabetes mellitus can ultimately result in various complications, including diabetic cardiomyopathy. In this case, cardiac dysfunction is characterized by metabolic disturbances such as impaired glucose oxidation and an increased reliance on fatty acid (FA) oxidation. Mitochondrial dysfunction has often been associated with the altered metabolic function in the diabetic heart, and may result from FA-induced lipotoxicity and uncoupling of oxidative phosphorylation. In this review, we address the metabolic changes in the diabetic heart, focusing on the loss of metabolic flexibility and cardiac mitochondrial function. We consider the alterations observed in mitochondrial substrate utilization, bioenergetics and dynamics, and highlight new areas of research which may improve our understanding of the cause and effect of cardiac mitochondrial dysfunction in diabetes. Finally, we explore how lifestyle (nutrition and exercise) and pharmacological interventions can prevent and treat metabolic and mitochondrial dysfunction in diabetes.COST Action MitoEAGL

The Norwegian Stroke in the Young Study (NOR-SYS): Rationale and design

Peer reviewe

2019 ESC/EAS guidelines for the management of dyslipidaemias : Lipid modification to reduce cardiovascular risk

Correction: Volume: 292 Pages: 160-162 DOI: 10.1016/j.atherosclerosis.2019.11.020 Published: JAN 2020Peer reviewe

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery