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Advances and Challenges in Biomarkers Use for Coronary Microvascular Dysfunction: From Bench to Clinical Practice.

ABSTRACT: Coronary microvascular dysfunction (CMD) is related to a broad variety of clinical scenarios in which cardiac microvasculature is morphologically and functionally affected, and it is associated with impaired responses to vasoactive stimuli. Although the prevalence of CMD involves about half of all patients with chronic coronary syndromes and more than 20% of those with acute coronary syndrome, the diagnosis of CMD is often missed, leading to the underestimation of its clinical importance. The established and validated techniques for the measurement of coronary microvascular function are invasive and expensive. An ideal method to assess endothelial dysfunction should be accurate, non-invasive, cost-effective and accessible. There are varieties of biomarkers available, potentially involved in microvascular disease, but none have been extensively validated in this heterogeneous clinical population. The investigation of potential biomarkers linked to microvascular dysfunction might improve the assessment of the diagnosis, risk stratification, disease progression and therapy response. This review article offers an update about traditional and novel potential biomarkers linked to CMD.

SUBMITTER: Rocco E

PROVIDER: S-EPMC8999821 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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Advances and Challenges in Biomarkers Use for Coronary Microvascular Dysfunction: From Bench to Clinical Practice.

Rocco Erica E Grimaldi Maria Chiara MC Maino Alessandro A Cappannoli Luigi L Pedicino Daniela D Liuzzo Giovanna G Biasucci Luigi Marzio LM

Journal of clinical medicine 20220406 7

Coronary microvascular dysfunction (CMD) is related to a broad variety of clinical scenarios in which cardiac microvasculature is morphologically and functionally affected, and it is associated with impaired responses to vasoactive stimuli. Although the prevalence of CMD involves about half of all patients with chronic coronary syndromes and more than 20% of those with acute coronary syndrome, the diagnosis of CMD is often missed, leading to the underestimation of its clinical importance. The es ...[more]

PMID: 35407662

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Project description:ImportanceLong-term use of anabolic androgenic steroids (AASs) is associated with a high risk of left ventricular hypertrophy, heart failure with reduced systolic function, and early sudden death, with the mechanism of progression being understudied. Early and persistent impaired myocardial microcirculation could be of clinical importance and a potential underlying mechanism of frequent and early cardiac disease among individuals with AAS use and a future potential target for intervention.ObjectiveTo investigate coronary microcirculation by measuring myocardial flow reserve (MFR) in men with current and former AAS use compared with controls with no prior AAS use, using cardiac rubidium 82 (82Rb) positron emission tomography/computed tomography (PET/CT).Design, setting, and participantsThis cross-sectional study included men involved in recreational strength training without established cardiovascular disease grouped according to their history of AAS use. The study was conducted November 24, 2021, to August 16, 2023.ExposureCardiac PET/CT with 82Rb was performed at rest and after adenosine-induced stress.Main outcome and measureThe primary outcome of this study was the MFR among the study groups; a secondary outcome was the coronary calcium score. By definition, impaired myocardial microcirculation was determined using a cutoff of MFR less than 2, and subclinically impaired microcirculation was determined using a cutoff of MFR less than 2.5.ResultsA total of 90 men (32 with current AAS use, 31 with former AAS use, and 27 controls) were included. Mean (SD) age was 35.1 (8.7) years. Elapsed duration since AAS cessation was a geometric mean of 1.5 (95% CI, 0.9-2.5) years. Eighteen men (58.1%) with former use discontinued AAS use more than 1 year before enrollment. Impaired MFR was present in those with current (6 [18.8%]) and former (1 [3.2%]) use, whereas no impairment was observed among the controls (P = .02). Subclinically impaired MFR was higher among men with current (9 [28.1%]) and former (8 [25.8%]) AAS use than the controls (1 [3.7%]) (P = .02). In a multivariable logistic regression model among men with former AAS use, every doubling of the accumulated weekly duration of AAS use (log2) was independently associated with a factor 2 increase in the risk of impaired MFR less than 2.5 (odds ratio, 2.1; 95% CI, 1.03-4.35; P = .04).Conclusions and relevanceIn this study, men with former AAS use displayed impaired MFR years after AAS cessation, suggesting impaired coronary microcirculation persists beyond active use.

Project description:Background In the absence of obstructive coronary stenoses, abnormality of noninvasive stress tests (NIT) in patients with chronic coronary syndromes may indicate myocardial ischemia of nonobstructive coronary arteries (INOCA). The differential prognosis of INOCA according to the presence of coronary microvascular dysfunction (CMD) and incremental prognostic value of CMD with intracoronary physiologic assessment on top of NIT information remains unknown. Methods and Results From the international multicenter registry of intracoronary physiologic assessment (ILIAS [Inclusive Invasive Physiological Assessment in Angina Syndromes] registry, N=2322), stable patients with NIT and nonobstructive coronary stenoses with fractional flow reserve >0.80 were selected. INOCA was diagnosed when patients showed positive NIT results. CMD was defined as coronary flow reserve ≤2.5. According to the presence of INOCA and CMD, patients were classified into 4 groups: group 1 (no INOCA nor CMD, n=116); group 2 (only CMD, n=90); group 3 (only INOCA, n=41); and group 4 (both INOCA and CMD, n=40). The primary outcome was major adverse cardiovascular events, a composite of all-cause death, target vessel myocardial infarction, or clinically driven target vessel revascularization at 5 years. Among 287 patients with nonobstructive coronary stenoses (fractional flow reserve=0.91±0.06), 81 patients (38.2%) were diagnosed with INOCA based on positive NIT. By intracoronary physiologic assessment, 130 patients (45.3%) had CMD. Regardless of the presence of INOCA, patients with CMD showed a significantly lower coronary flow reserve and higher hyperemic microvascular resistance compared with patients without CMD (P<0.001 for all). The cumulative incidence of major adverse cardiovascular events at 5 years were 7.4%, 21.3%, 7.7%, and 34.4% in groups 1 to 4. By documenting CMD (groups 2 and 4), intracoronary physiologic assessment identified patients at a significantly higher risk of major adverse cardiovascular events at 5 years compared with group 1 (group 2: adjusted hazard ratio [HRadjusted], 2.88; 95% CI, 1.52-7.19; P=0.024; group 4: HRadjusted, 4.00; 95% CI, 1.41-11.35; P=0.009). Conclusions In stable patients with nonobstructive coronary stenoses, a diagnosis of INOCA based only on abnormal NIT did not identify patients with higher risk of long-term cardiovascular events. Incorporating intracoronary physiologic assessment to NIT information in patients with nonobstructive disease allowed identification of patient subgroups with up to 4-fold difference in long-term cardiovascular events. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04485234.

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Advances and Challenges in Biomarkers Use for Coronary Microvascular Dysfunction: From Bench to Clinical Practice.

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Advances and Challenges in Biomarkers Use for Coronary Microvascular Dysfunction: From Bench to Clinical Practice.

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