Expanding landscape of coronary microvascular disease in co-morbid conditions: Metabolic disease and beyond.

Coronary microvascular disease (CMD) and impaired coronary blood flow control are defects that occur early in the pathogenesis of heart failure in cardiometabolic conditions, prior to the onset of atherosclerosis. In fact, recent studies have shown that CMD is an independent predictor of cardiac morbidity and mortality in patients with obesity and metabolic disease. CMD is comprised of functional, structural, and mechanical impairments that synergize and ultimately reduce coronary blood flow in metabolic disease and in other co-morbid conditions, including transplant, autoimmune disorders, chemotherapy-induced cardiotoxicity, and remote injury-induced CMD. This review summarizes the contemporary state-of-the-field related to CMD in metabolic and these other co-morbid conditions based on mechanistic data derived mostly from preclinical small- and large-animal models in light of available clinical evidence and given the limitations of studying these mechanisms in humans. In addition, we also discuss gaps in current understanding, emerging areas of interest, and opportunities for future investigations in this field.

Prognostic value of myocardial flow reserve vs corrected myocardial flow reserve in patients without obstructive coronary artery disease.

BACKGROUND: Myocardial flow reserve (MFR) by positron emission tomography (PET) is a validated measure of cardiovascular risk. Elevated resting rate pressure product (RPP = heart rate x systolic blood pressure) can cause high resting myocardial blood flow (MBF), resulting in reduced MFR despite normal/near-normal peak stress MBF. When resting MBF is high, it is not known if RPP-corrected MFR (MFRcorrected) helps reclassify CV risk. We aimed to study this question in patients without obstructive coronary artery disease (CAD). METHODS: We retrospectively studied patients referred for rest/stress cardiac PET at our center from 2006 to 2020. Patients with abnormal perfusion (summed stress score >3) or prior coronary artery bypass grafting (CABG) were excluded. MFRcorrected was defined as stress MBF/corrected rest MBF where corrected rest MBF = rest MBF x 10,000/RPP. The primary outcome was major cardiovascular events (MACE): cardiovascular death or myocardial infarction. Associations of MFR and MFRcorrected with MACE were assessed using unadjusted and adjusted Cox regression. RESULTS: 3276 patients were followed for a median of 7 (IQR 3-12) years. 1685 patients (51%) had MFR <2.0, and of those 366 (22%) had an MFR ≥2.0 after RPP correction. MFR <2.0 was associated with an increased absolute risk of MACE (HR 2.24 [1.79-2.81], P < 0.0001). Among patients with MFR <2.0, the risk of MACE was not statistically different between patients with an MFRcorrected ≥2.0 compared with those with MFRcorrected <2.0 (1.9% vs 2.3% MACE/year, HR 0.84 [0.63-1.13], P = 0.26) even after adjustment for confounders (P = 0.66). CONCLUSIONS: In patients without overt obstructive CAD and MFR< 2.0, there was no significant difference in cardiovascular risk between patients with discordant (≥2.0) and concordant (<2) MFR following RPP correction. This suggests that RPP-corrected MFR may not consistently provide accurate risk stratification in patients with normal perfusion and MFR <2.0. Stress MBF and uncorrected MFR should be reported to more reliably convey cardiovascular risk beyond perfusion results.

Impact of Isolated Coronary Microvascular Disease Diagnosed Using Various Measurement Modalities on Prognosis: An Updated Systematic Review and Meta-Analysis.

INTRODUCTION: The main aim of this study was to investigate the impact of isolated coronary microvascular disease (CMD) as diagnosed via various modalities on prognosis. METHODS: A systematic literature review of PubMed, Embase, and Cochrane Library databases was conducted to identify relevant studies published up to March 2023. Included studies were required to measure coronary microvascular function and report outcomes in patients without obstructive coronary artery disease (CAD) or any other cardiac pathological characteristics. The primary endpoint was all-cause mortality, and the secondary endpoint was a major adverse cardiac event (MACE). Pooled effects were calculated using random effects models. RESULTS: A total of 27 studies comprising 18,204 subjects were included in the meta-analysis. Indices of coronary microvascular function measurement included coronary angiography-derived index of microcirculatory resistance (caIMR), hyperemic microcirculatory resistance (HMR), coronary flow reserve (CFR), and so on. Patients with isolated CMD exhibited a significantly higher risk of mortality (OR: 2.97, 95% CI, 1.91-4.60, p < 0.0001; HR: 3.38, 95% CI, 1.77-6.47, p = 0.0002) and MACE (OR: 5.82, 95% CI, 3.65-9.29, p < 0.00001; HR: 4.01, 95% CI, 2.59-6.20, p < 0.00001) compared to those without CMD. Subgroup analysis by measurement modality demonstrated consistent and robust pooled effect estimates in various subgroups. CONCLUSION: CMD is significantly associated with an elevated risk of mortality and MACE in patients without obstructive CAD or any other identifiable cardiac pathologies. The utilization of various measurement techniques may have potential advantages in the management of isolated CMD.

HbA1c is related to microcirculation blood perfusion in patients with coronary microvascular disease using stress perfusion cardiac magnetic resonance: An observational study.

BACKGROUND: In coronary microvascular disease (CMD) patients, the incidence of major adverse cardiovascular events (MACEs) in patients with myocardial perfusion reserve index (MPRI) ≤ 1.47 is three times higher than that in MPRI > 1.47. We investigated whether the increase of glycated hemoglobin A1c (HbA1c) could increase the risk of MPRI ≤1.47 in diabetic and non-diabetic patients. METHODS: From November 2019, patients with ischemic symptoms but without obstructive coronary disease were screened. Use MPRI measured by stress perfusion cardiac magnetic resonance (CMR) to reflect microcirculation blood perfusion, and MPRI <2.5 were included. The patients were divided into two groups based on MPRI was greater or <1.47. The risk factors for CMD were explored using logistic regression analysis. RESULTS: A total of 80 patients with an MPRI of 1.69 ± 0.79 were included. CMD patients with an MPRI of ≤1.47(n = 33) were higher than MPRI of >1.47(n = 47) in age, presence of diabetes mellitus, fasting blood glucose levels and HbA1c levels (P < 0.05). In non-diabetic patients, increased HbA1c was associated with the risk of MPRI≤1.47 (OR = 0.017, 95%CI: 0.050-1.107, P = 0.045). Compared with non-diabetic patients with HbA1c < 6.0, non-diabetic patients with HbA1c ≥ 6.0 increased the risk of MPRI of ≤1.47 (OR = 0.219, 95%CI: 0.069-0.697, P = 0.010). In diabetic patients, HbA1c was not associated with the risk of MPRI of ≤1.47 (OR = 1.043, 95%CI: 0.269, 4.044, P = 0.952). And compared with non-diabetic patients with HbA1c <6.0, diabetic patients with HbA1c <6.0 (OR = 0.917, 95%CI: 0.233-3.610, P = 0.901) or ≥6.0 (OR = 0.326, 95%CI: 0.073-1.446, P = 0.140), the risk of MPRI ≤ 1.47 was not further increased. CONCLUSIONS: In non-diabetic patients, elevated HbA1c is related to MPRI≤1.47(a value increased incidence of MACEs). Therefore, in patients with undiagnosed diabetes, early management of glycosylated hemoglobin is very important. TRIAL REGISTRATION: This clinical trial has been registered in the Chinese clinical Trial Registry with an identifier: ChiCTR1900025810.

Atherosclerosis in Systemic Lupus Erythematosus.

PURPOSE OF THE REVIEW: Systemic lupus erythematosus (SLE) patients are at increased risk of cardiovascular disease (CVD) compared to the general population, despite most patients being young females, who are not classically considered to be at high risk for cardiovascular disease using traditional risk assessment tools. The purpose of this review is to discuss the pathophysiology of atherosclerosis in SLE and raise awareness of the relationship between SLE and CVD. RECENT FINDINGS: The increased risk of CVD in SLE patients is multifactorial, due to proatherogenic lipid profiles, immune dysregulation and inflammation, side effects of lupus treatment, and microvascular dysfunction. Conventional CV risk models often underperform in the identification of SLE patients at high risk of atherosclerosis. The use of non-invasive imaging serves as a strategy to identify patients with evidence of subclinical CVD and in the evaluation of symptomatic patients. Identification of subclinical atherosclerosis allows for aggressive management of CV risk factors. SLE patients experience an increased risk of atherosclerotic CVD, which is not solely explained by traditional CV risk factors. It is imperative that clinicians are aware of this association to implement prompt detection and treatment of atherosclerotic CVD in SLE patients.

Coronary microvascular disease in hypertrophic and infiltrative cardiomyopathies.

Pathologic hypertrophy of the cardiac muscle is a commonly encountered phenotype in clinical practice, associated with a variety of structural and non-structural diseases. Coronary microvascular disease is considered to play an important role in the natural history of this pathological phenotype. Non-invasive imaging modalities, most prominently positron emission tomography and cardiac magnetic resonance, have provided insights into the pathophysiological mechanisms of the interplay between hypertrophy and the coronary microvasculature. This article summarizes the current knowledge on coronary microvascular dysfunction in the most frequently encountered forms of pathologic hypertrophy.

The relationship between triglyceride/high-density lipoprotein cholesterol ratio and coronary microvascular disease.

BACKGROUND: As a novel marker of insulin resistance, the ratio of triglyceride/high-density lipoprotein cholesterol (TG/HDL-C) has been recently reported to be related to the occurrence of coronary artery diseases. However, no research has been conducted to probe whether the TG/HDL-C ratio is associated with the occurrence of coronary microvascular disease (CMVD). AIM: This study investigates the association between the TG/HDL-C ratio and the occurrence of CMVD. METHODS: This study included 175 patients diagnosed with CMVD in the Department of Cardiology of our hospital from October 2017 to October 2021 as the study group and 175 patients with no chest pain, no history of cardiovascular disease and drug use, and negative results of exercise treadmill testing as the non-CMVD group. The clinical data of the two groups were compared. In addition, the risk factors of CMVD were analyzed with logistic regression, and the efficacy of independent risk factors in predicting CMVD was analyzed with a receiver operating characteristic (ROC) curve. RESULTS: Compared with those in the non-CMVD group, the proportion of females, the incidence of hypertension and type 2 diabetes, the level of platelet count, TG, and C-reactive protein, and the ratio of TG/HDL-C were increased in the CMVD group, accompanied by decreased levels of albumin and HDL-C (P < 0.05). Logistic regression results revealed C-reactive protein (the area under the ROC curve [AUC] value: 0.754; 95% confidence interval [CI]: 0.681-0.827), sex (the AUC value: 0.651; 95%CI: 0.571-0.730), albumin (the AUC value: 0.722; 95%CI: 0.649-0.794), and TG/HDL-C ratio (the AUC value: 0.789; 95%CI: 0.718-0.859) as the independent risk factors of CMVD. CONCLUSION: The TG/HDL-C ratio is an independent risk factor for the occurrence of CMVD.

Chinese patent medicines for coronary microvascular disease: clinical evidence and potential mechanisms.

Coronary microvascular disease (CMVD) is a high risk factor for many cardiovascular events. Due to the limited understanding of its pathophysiological mechanism, modern medicine still lacks therapeutic drugs for CMVD. Existing clinical studies have shown that traditional Chinese medicine (TCM) can effectively improve the clinical symptoms and quality of life of CMVD patients. As an indispensable part of TCM, Chinese patent medicines (CPMs) are widely used in clinical practice. In the face of numerous oral CPMs for treatment of CMVD, how to choose a reasonable medication regimen is one of the important issues in clinic. Based on this, this paper reviewed the clinical efficacy and recommended level of 12 CPMs in the treatment of CMVD, which are recommended by expert consensus on diagnosis and treatment of coronary microvascular disease with integrated Chinese and Western medicine (WM). In addition, this study also systematically summarized the possible mechanisms of CPMs in the treatment of CMVD by protecting coronary microvascular endothelial cells, improving vascular endothelial function, inhibiting inflammation, reducing oxidative stress, promoting angiogenesis, and improving hemorheology, aiming to provide meaningful information for its clinical application.

The Role of Imaging in Preventive Cardiology in Women.

PURPOSE OF REVIEW: The prevalence of CVD in women is increasing and is due to the increased prevalence of CV risk factors. Traditional CV risk assessment tools for prevention have failed to accurately determine CVD risk in women. CAC has shown to more precisely determine CV risk and is a better predictor of CV outcomes. Coronary CTA provides an opportunity to determine the presence of CAD and initiate prevention in women presenting with angina. Identifying women with INOCA due to CMD with use of cPET or cMRI with MBFR is vital in managing these patients. This review article outlines the role of imaging in preventive cardiology for women and will include the latest evidence supporting the use of these imaging tests for this purpose. RECENT FINDINGS: CV mortality is higher in women who have more extensive CAC burden. Women have a greater prevalence of INOCA which is associated with higher MACE. INOCA is due to CMD in most cases which is associated with traditional CVD risk factors. Over half of these women are untreated or undertreated. Recent study showed that stratified medical therapy, tailored to the specific INOCA endotype, is feasible and improves angina in women. Coronary CTA is useful in the setting of women presenting with acute chest pain to identify CAD and initiate preventive therapy. CAC confers greater relative risk for CV mortality in women versus (vs.) men. cMRI or cPET is useful to assess MBFR to diagnose CMD and is another useful imaging tool in women for CV prevention.

Accelerated fatty acid composition MRI of epicardial adipose tissue: Development and application to eplerenone treatment in a mouse model of obesity-induced coronary microvascular disease.

PURPOSE: To develop an accelerated MRI method to quantify the epicardial adipose tissue (EAT) fatty acid composition (FAC) and test the hypothesis that eplerenone (EPL) shifts the EAT FAC toward unsaturation in obese mice. METHODS: Undersampled multi-echo gradient echo imaging employing a dictionary-based compressed-sensing reconstruction and iterative decomposition with echo asymmetry and least-squares-based mapping (IDEAL) was developed, validated, and used to study EAT in obese mice scanned at 7T. Fully sampled and rate 2, 2.5, 3, and 3.5 undersampled image data were acquired, reconstructed, and assessed using RMSE and structural similarity (SSIM). Two groups of mice were studied: untreated (control, n = 10) and EPL-treated (n = 10) mice fed a high-fat high-sucrose diet. MRI included imaging of EAT FAC, EAT volume, and myocardial perfusion reserve. RESULTS: Rate 3 acceleration provided RMSE <5% and structural similarity >0.85 for FAC MRI. After 6 weeks of diet, EPL-treated compared to untreated mice had a reduced EAT saturated fatty acid fraction (0.27 ± 0.09 vs. 0.39 ± 0.07, P < 0.05) and increased EAT unsaturation degree (4.37 ± 0.32 vs. 3.69 ± 0.58, P < 0.05). Also, EAT volume in EPL-treated compared to untreated mice was reduced (8.1 ± 0.6 mg vs. 11.4 ± 0.7 mg, P < 0.01), and myocardial perfusion reserve was improved (1.83 ± 0.15 vs. 1.61 ± 0.17, P < 0.05). CONCLUSION: Rate 3 accelerated FAC MRI enabled accurate quantification of EAT FAC in mice. EPL treatment shifted the EAT FAC toward increased unsaturation and was associated with improvement of coronary microvascular function.

Coronary vasomotor dysfunction portends worse outcomes in patients with breast cancer.

BACKGROUND: Impaired MFR in the absence of flow-limiting CAD is associated with adverse events. Cardiovascular disease is an important cause of morbidity and mortality in patients with breast cancer. We sought to test the utility of MFR to predict outcomes in a cohort of patients with breast cancer. METHODS: We retrospectively studied consecutive patients with breast cancer or breast cancer survivors who underwent cardiac stress PET imaging from 2006 to 2017 at Brigham and Women's Hospital. Patients with a history of clinically overt CAD, LVEF < 45%, or abnormal myocardial perfusion were excluded. Subjects were followed from time of PET to the occurrence of a first major adverse cardiovascular event (MACE) and all-cause death. RESULTS: The final cohort included 87 patients (median age 69.0 years, 98.9% female, mean MFR 2.05). Over a median follow-up of 7.6 years after PET, the lowest MFR tertile was associated with higher cumulative incidence of MACE (adjusted subdistribution hazard ratio 4.91; 95% CI 1.68-14.38; p = 0.004) when compared with the highest MFR tertile. CONCLUSIONS: In patients with breast cancer, coronary vasomotor dysfunction was associated with incident cardiovascular events. MFR may have potential as a risk stratification biomarker among patients with/survivors of breast cancer.

Nuclear Cardiology in Women and Underrepresented Minority Populations.

PURPOSE OF REVIEW: To outline sex-specific features of coronary artery disease (CAD) that should be considered in the assessment of women, including those from ethnic minority populations with suspected stable ischemic heart disease (IHD). Second, to determine the latest nuclear imaging tools available to assess microvascular CAD. RECENT FINDINGS: Latest studies indicate that women are more likely to have ischemia with no obstructive coronary arteries (INOCA) and paradoxically have worse outcomes. Therefore, the evaluation of women with suspected IHD should include assessing microvascular and epicardial coronary circulation. The prevalence of CAD is increasing in younger women due to the increased cardiovascular disease (CVD) risk burden. CAD is often underrecognized in these patients. There is increasing recognition that INOCA is not benign and should be accurately diagnosed and managed. Nuclear imaging assesses the full spectrum of CAD from microvascular CAD to multivessel obstructive epicardial CAD. Further research on myocardial blood flow (MBF) assessment with PET MPI is needed.

Untangling the pathophysiologic link between coronary microvascular dysfunction and heart failure with preserved ejection fraction.

Coronary microvascular disease (CMD), characterized by impaired coronary flow reserve (CFR), is a common finding in patients with stable angina. Impaired CFR, in the absence of obstructive coronary artery disease, is also present in up to 75% of patients with heart failure with preserved ejection fraction (HFpEF). Heart failure with preserved ejection fraction is a heterogeneous syndrome comprising distinct endotypes and it has been hypothesized that CMD lies at the centre of the pathogenesis of one such entity: the CMD-HFpEF endotype. This article provides a contemporary review of the pathophysiology underlying CMD, with a focus on the mechanistic link between CMD and HFpEF. We discuss the central role played by subendocardial ischaemia and impaired lusitropy in the development of CMD-HFpEF, as well as the clinical and research implications of the CMD-HFpEF mechanistic link. Future prospective follow-up studies detailing outcomes in patients with CMD and HFpEF are much needed to enhance our understanding of the pathological processes driving these conditions, which may lead to the development of physiology-stratified therapy to improve the quality of life and prognosis in these patients.

H2O2 Mediates VEGF- and Flow-Induced Dilations of Coronary Arterioles in Early Type 1 Diabetes: Role of Vascular Arginase and PI3K-Linked eNOS Uncoupling.

In diabetes, the enzyme arginase is upregulated, which may compete with endothelial nitric oxide (NO) synthase (eNOS) for their common substrate L-arginine and compromise NO-mediated vasodilation. However, this eNOS uncoupling can lead to superoxide production and possibly vasodilator hydrogen peroxide (H2O2) formation to compensate for NO deficiency. This hypothesis was tested in coronary arterioles isolated from pigs with 2-week diabetes after streptozocin injection. The NO-mediated vasodilation induced by flow and VEGF was abolished by NOS inhibitor L-NAME and phosphoinositide 3-kinase (PI3K) inhibitor wortmannin but was not affected by arginase inhibitor Nω-hydroxy-nor-L-arginine (nor-NOHA) or H2O2 scavenger catalase in control pigs. With diabetes, this vasodilation was partially blunted, and the remaining vasodilation was abolished by catalase and wortmannin. Administration of L-arginine or nor-NOHA restored flow-induced vasodilation in an L-NAME sensitive manner. Diabetes did not alter vascular superoxide dismutase 1, catalase, and glutathione peroxidase mRNA levels. This study demonstrates that endothelium-dependent NO-mediated coronary arteriolar dilation is partially compromised in early type 1 diabetes by reducing eNOS substrate L-arginine via arginase activation. It appears that upregulated arginase contributes to endothelial NO deficiency in early diabetes, but production of H2O2 during PI3K-linked eNOS uncoupling likely compensates for and masks this disturbance.

Role of coronary microvascular dysfunction in heart failure with preserved ejection fraction.

Heart failure with preserved ejection fraction (HFpEF) is one of the greatest unmet needs in modern medicine. The lack of an appropriate therapy may reflect the lack of an accurate comprehension of its pathophysiology. Coronary microvascular rarefaction in HFpEF was first hypothesized in an autopsy study that showed how HFpEF patients had lower microvascular density and more myocardial fibrosis than control subjects. This was later confirmed in vivo when it was noted that HFpEF is associated with reduced myocardial flow reserve (MFR) at single photon emission computed tomography (SPECT) and that coronary microvascular dysfunction may play a role in HFpEF disease processes. HFpEF patients were found to have lower coronary flow reserve (CFR) and a higher index of microvascular resistance (IMR). What is the cause of microvascular dysfunction? In 2013, a new paradigm for the pathogenesis of HFpEF has been proposed. It has been postulated that the presence of a proinflammatory state leads to coronary microvascular endothelial inflammation and reduced nitric oxide bioavailability, which ultimately results in heart failure. Recently, it has also been noted that inflammation is the main driver of HFpEF, but via an increase in inducible nitric oxide synthase (iNOS) resulting in a decrease in unfolded protein response. This review summarizes the current evidence on the etiology of coronary microvascular dysfunction in HFpEF, focusing on the role of inflammation and its possible prevention and therapy.

Left ventricular diastolic dysfunction in women with nonobstructive ischemic heart disease: insights from magnetic resonance imaging and spectroscopy.

Ischemic heart disease, in the absence of obstructive coronary artery disease, is prevalent in women and constitutes a major risk factor for developing major adverse cardiovascular events, including myocardial infarction, stroke, and heart failure. For decades, diagnosis was considered benign and often minimized; however, it is now known that this etiology carries much risk and is a significant burden to the health care system. This review summarizes the current state of knowledge on nonobstructive ischemic heart disease (NOIHD), the association between NOIHD and left ventricular diastolic dysfunction, potential links between NOIHD and the development of heart failure with preserved ejection fraction (HFpEF), and therapeutic options and knowledge gaps for patients living with NOIHD.

Alterations in genes associated with cytosolic RNA sensing in whole blood are associated with coronary microvascular disease in SLE.

Systemic lupus erythematosus (SLE) patients are 90% women and over three times more likely to die of cardiovascular disease than women in the general population. Chest pain with no obstructive cardiac disease is associated with coronary microvascular disease (CMD), where narrowing of the small blood vessels can lead to ischemia, and frequently reported by SLE patients. Using whole blood RNA samples, we asked whether gene signatures discriminate SLE patients with coronary microvascular dysfunction (CMD) on cardiac MRI (n=4) from those without (n=7) and whether any signaling pathway is linked to the underlying pathobiology of SLE CMD. RNA-seq analysis revealed 143 differentially expressed (DE) genes between the SLE and healthy control (HC) groups, with virus defense and interferon (IFN) signaling being the key pathways identified as enriched in SLE as expected. We next conducted a comparative analysis of genes differentially expressed in SLE-CMD and SLE-non-CMD relative to HC samples. Our analysis highlighted differences in IFN signaling, RNA sensing and ADP-ribosylation pathways between SLE-CMD and SLE-non-CMD. This is the first study to investigate possible gene signatures associating with CMD in SLE, and our data strongly suggests that distinct molecular mechanisms underly vascular changes in CMD and non-CMD involvement in SLE.

Patients With Coronary Microvascular Dysfunction Have Less Circulating α-Klotho.

BACKGROUND: Coronary microvascular dysfunction (CMD) represents an early functional characteristic of coronary vascular aging. Klotho (α-klotho) is a circulating protein inversely linked to physiological aging. We examined low klotho as a potential marker for vascular aging in patients with CMD and no coronary artery disease. METHODS AND RESULTS: Patients undergoing nonurgent angiogram for chest pain who had no coronary artery disease underwent invasive coronary microvascular and endothelial function testing. CMD was defined by ≤50% increase in coronary blood flow (percentage change in coronary blood flow) in response to intracoronary acetylcholine or coronary flow reserve ≤2. Fresh arterial whole blood was used to analyze circulating endothelial progenitor cells with flow cytometry. Stored arterial plasma was used for klotho analysis by ELISA. Participants with CMD (n=62) were compared with those without CMD (n=36). Those with CMD were age 55±10 years (versus 51±11 years; P=0.07) and 73% women (versus 81%; P=0.38). Traditional risk factors for coronary artery disease were similar between groups. Patients with CMD had less klotho (0.88±1.50 versus 1.75±2.38 ng/mL; P=0.03), and the odds of low klotho in CMD were significant in a logistic regression model after adjusting for traditional cardiovascular risk factors (odds ratio [OR], 0.80 [95% CI, 0.636-0.996]; P=0.05). Higher klotho was associated with higher numbers of endothelial progenitor cells with vascular regenerative potential (CD34+ and CD34+CD133+KDR+). Among a subgroup of patients with atherosclerotic cardiovascular disease risk <5% (n=58), CMD remained associated with lower klotho (OR, 0.80 [95% CI, 0.636-0.996]; P=0.047). CONCLUSIONS: Klotho may be a biomarker for CMD and may be a therapeutic target for groups of patients without significant traditional cardiovascular risk.

Inflammation and coronary microvascular disease: relationship, mechanism and treatment.

Coronary microvascular disease (CMVD) is common in patients with cardiovascular risk factors and is linked to an elevated risk of adverse cardiovascular events. Although modern medicine has made significant strides in researching CMVD, we still lack a comprehensive understanding of its pathophysiological mechanisms due to its complex and somewhat cryptic etiology. This greatly impedes the clinical diagnosis and treatment of CMVD. The primary pathological mechanisms of CMVD are structural abnormalities and/or dysfunction of coronary microvascular endothelial cells. The development of CMVD may also involve a variety of inflammatory factors through the endothelial cell injury pathway. This paper first reviews the correlation between the inflammatory response and CMVD, then summarizes the possible mechanisms of inflammatory response in CMVD, and finally categorizes the drugs used to treat CMVD based on their effect on the inflammatory response. We hope that this paper draws attention to CMVD and provides novel ideas for potential therapeutic strategies based on the inflammatory response.