Coronary slow flow and angiography-derived index of microcirculatory resistance as prognostic predictors in patients with angina and normal coronary arteries: a retrospective cohort study.

BACKGROUND: This study aims to investigate prognostic implications of coronary slow flow (CSF) and angiography-derived index of microcirculatory resistance (caIMR) in patients with angina and normal coronary arteries. METHODS: A total of 582 patients were enrolled with angiographically normal coronary arteries. caIMR was calculated using a commercial software. Patients were followed up for a median of 45 months. The primary endpoint was defined as major adverse cardiovascular events (MACEs) comprising death, myocardial infarction and readmission for angina or heart failure. RESULTS: CSF was diagnosed when TIMI grade 2 flow presented in at least one coronary artery. Multivariate analysis indicated TIMI-flow-based determination of CSF was not significantly associated with MACEs [hazard ratio (HR): 2.14; 95% confidence interval (CI): 0.87-5.31; p = 0.099), while caIMR >42 (HR: 2.53; 95% CI: 1.02-6.32; p = 0.047) were independent predictors of MACEs. Incorporation of caIMR improved the area under the curve from 0.587 to 0.642. CONCLUSIONS: caIMR was an independent prognostic factor of long-term cardiovascular events in patients with CSF. Evaluation of caIMR improved the risk stratification of patients with angiographically-normal coronary arteries.

Long-Term Clinical-Pathologic Results of Enzyme Replacement Therapy in Prehypertrophic Fabry Disease Cardiomyopathy.

BACKGROUND: The limited ability of enzyme replacement therapy (ERT) in removing globotriaosylceramide from cardiomyocytes is recognized for advanced Fabry disease cardiomyopathy (FDCM). Prehypertrophic FDCM is believed to be cured or stabilized by ERT. However, no pathologic confirmation is available. We report here on the long-term clinical-pathologic impact of ERT on prehypertrophic FDCM. METHODS AND RESULTS: Fifteen patients with Fabry disease with left ventricular maximal wall thickness ≤10.5 mm at cardiac magnetic resonance required endomyocardial biopsy because of angina and ventricular arrhythmias. Endomyocardial biopsy showed coronary small-vessel disease in the angina cohort, and vacuoles in smooth muscle cells and cardiomyocytes ≈20% of the cell surface containing myelin bodies at electron microscopy. Patients received α-agalsidase in 8 cases, and ß-agalsidase in 7 cases. Both groups experienced symptom improvement except 1 patients treated with α-agalsidase and 1 treated with ß-agalsidase. After ERT administration ranging from 4 to 20 years, all patients had control cardiac magnetic resonance and left ventricular endomyocardial biopsy because of persistence of symptoms or patient inquiry on disease resolution. In 13 asymptomatic patients with FDCM, left ventricular maximal wall thickness and left ventricular mass, cardiomyocyte diameter, vacuole surface/cell surface ratio, and vessels remained unchanged or minimally increased (left ventricular mass increased by <2%) even after 20 years of observation, and storage material was still present at electron microscopy. In 2 symptomatic patients, FDCM progressed, with larger and more engulfed by globotriaosylceramide myocytes being associated with myocardial virus-negative lymphocytic inflammation. CONCLUSIONS: ERT stabilizes storage deposits and myocyte dimensions in 87% of patients with prehypertrophic FDCM. Globotriaosylceramide is never completely removed even after long-term treatment. Immune-mediated myocardial inflammation can overlap, limiting ERT activity.

[Clinical comprehensive evaluation of Shexiang Tongxin Dropping Pills].

Based on literature and questionnaire research, related evidence and related data on Shexiang Tongxin Dropping Pills were collected in terms of safety, effectiveness, economy, innovation, suitability, and accessibility. In addition, multi-criteria decision analysis(MCDA) model was used to comprehensively evaluate the clinical value of Shexiang Tongxin Dropping Pills. Quality control was carried out strictly based on evidence-based medicine evaluation. Shexiang Tongxin Dropping Pills were recommended for stable fatigue angina of coronary heart disease with Qi deficiency and blood stasis by guidelines and experts. The conventional treatment of western medicine adds Shexiang Tongxin Dropping Pills to reduce the frequency of angina attacks, shorten the duration, improve exercise tolerance, and improve the quality of life and Chinese symptoms, and the effectiveness is rated as grade A. Adverse reactions are mostly general adverse reactions, and no serious adverse reactions have been reported, consistent with the known risks listed in the instruction for adverse events, contraindications, and precautions. The safety is rated as grade A, and the daily cost is 7.74 yuan. The cost-effectiveness shows that it is a treatment regimen with pharmacoeconomic advantages, and the economic performance is rated as grade A. According to specialist research, Shexiang Tongxin Dropping Pills have good clinical innovation and service innovation, and innovation is rated as grade A. There are no special storage conditions, medicinal material ingredients, or other restrictions, and the clinical use meets the specifications of the medication guidelines. The suitability is rated as grade A. The price level, availability, and affordability of drugs are generally good, and the accessibility is rated as grade A. The clinical value of Shexiang Tongxin Dropping Pills is great.

Association of relative hand grip strength with myocardial infarction and angina pectoris in the Korean population: a large-scale cross-sectional study.

BACKGROUND: Low hand grip strength (HGS) is associated with the risk of cardiovascular diseases, but the association between HGS and myocardial infarction/angina pectoris (MIAP) is unclear. Furthermore, there have been no studies examining the associations of MIAP with anthropometric indices, absolute HGS indices, and relative HGS indices calculated by dividing absolute HGS values by body mass index (BMI), waist circumference (WC), waist-to-height ratio (WHtR), or weight values. Therefore, the objective of this study was to examine the associations of MIAP with absolute and relative HGS combined with several anthropometric indices. METHODS: In this large-scale cross-sectional study, a total of 12,963 subjects from the National Health and Nutrition Examination Survey were included. Odds ratios and 95% confidence intervals for the associations of MIAP with anthropometric indices, absolute HGS indices, and relative HGS indices were computed from binary logistic regression models. We built 3 models: a crude model, a model that was adjusted for age (Model 1), and a model that was adjusted for other relevant covariates (Model 2). RESULTS: For men, the average age was 61.55 ± 0.16 years in the MIAP group and 66.49 ± 0.61 years in the non-MIAP group. For women, the average age was 61.99 ± 0.14 years in the MIAP group and 70.48 ± 0.61 years in the non-MIAP group. For both sexes, the MIAP group had lower diastolic blood pressure, shorter stature, greater WC, and a greater WHtR than did the non-MIAP group, and women tended to have greater systolic blood pressure, weight, and BMI than in men. HGS was strongly associated with the risk of MIAP in the Korean population. In men, relative HGS indices combined with WC and the WHtR had greater associations with MIAP than did the anthropometric indices and absolute HGS indices. However, in women, anthropometric indices, including weight, BMI, WC, and WHtR, were more strongly associated with MIAP than were absolute and relative HGS indices, unlike in men. When comparing absolute and relative HGS indices in women, relative HGS indices combined with BMI and weight was more strongly related to MIAP than was absolute HGS indices. CONCLUSIONS: MIAP might be better identified by relative HGS than absolute HGS in both sexes. The overall magnitudes of the associations of MIAP with absolute and relative HGS are greater in men than in women.

Variation in Health Status With Invasive vs Conservative Management of Chronic Coronary Disease.

BACKGROUND: The ISCHEMIA trial found that patients with chronic coronary disease randomized to invasive strategy had better health status than those randomized to conservative strategy. It is unclear how best to translate these population-level results to individual patients. OBJECTIVES: The authors sought to identify patient characteristics associated with health status from invasive and conservative strategies, and develop a prediction algorithm for shared decision-making. METHODS: One-year disease-specific health status was assessed in ISCHEMIA with the Seattle Angina Questionnaire (SAQ) Summary Score (SAQ SS) and Angina Frequency, Physical Limitations (PL), and Quality of Life (QL) domains (range 0-100, higher = less angina/better health status). RESULTS: Among 4,617 patients from 320 sites in 37 countries, mean SAQ SS was 74.1 ± 18.9 at baseline and 85.7 ± 15.6 at 1 year. Lower baseline SAQ SS and younger age were associated with better 1-year health status with invasive strategy (P interaction = 0.009 and P interaction = 0.004, respectively). For the individual domains, there were significant treatment interactions for baseline SAQ score (Angina Frequency, PL), age (PL, QL), anterior ischemia (PL), and number of baseline antianginal medications (QL), with more benefit of invasive in patients with worse baseline health status, younger age, anterior ischemia, and on more antianginal medications. Parsimonious prediction models were developed for 1-year SAQ domains with invasive or conservative strategies to support shared decision-making. CONCLUSIONS: In the management of chronic coronary disease, individual patient characteristics are associated with 1-year health status, with younger age and poorer angina-related health status showing greater benefit from invasive management. This prediction algorithm can support the translation of the ISCHEMIA trial results to individual patients. (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches [ISCHEMIA]; NCT01471522).

Giant unruptured sinus of Valsalva aneurysms causing angina pectoris.

BACKGROUND: Sinus of Valsalva aneurysm (SVA) is a rare cardiac anomaly which can be congenital or acquired. Patients with SVA are commonly asymptomatic when the occupying effect of SVA is insignificant, while ruptured SVA usually causes severe symptoms including heart failure and myocardial ischemia. CASE PRESENTATION: We present an unusual case of a 64-year-old female manifesting with exertional dyspnea as well as angina pectoris for three months. Echocardiography and cardiac computed tomographic angiography confirmed unruptured left-coronary and non-coronary SVAs. The left anterior descending artery and left circumflex artery were stretched and compressed by the SVA which causing myocardial ischemia. The patient finally received aortic root replacement (Bentall procedure) and got symptom relieved. CONCLUSIONS: Giant unruptured SVA originating from left coronary sinus is extremely rare. Our case highlights that giant SVA should be considered in cases with angina pectoris. Echocardiography and coronary computed tomographic angiography are useful and important for diagnosis. Surgery is highly recommended in patients with SVA.

The Causal Relationship between Angina Pectoris and Gout Based on Two Sample Mendelian Randomization.

Purpose: Two-sample Mendelian randomization (MR) was conducted to assess the causal relationship between angina pectoris and gout. Material and Methods. Based on genome-wide association studies, single nucleotide polymorphisms (SNPs) that were closely associated with gout were selected from the UK Biobank-Neale Lab (ukb-a-107) as genetic instrumental variables. Considering that gout is characterized by elevated blood uric acid levels, SNPs related to blood uric acid levels were screened from BioBank Japan (bbj-a-57) as auxiliary gene instrumental variables. SNPs closely associated with angina pectoris onset were screened from the FINN dataset (finn-b-I9_ANGINA) as outcome variables. Two-sample MR was conducted, with inverse variance weighting (IVW) of the random effects model as the primary result, along with the weighted median method (WME) and the MR-Egger regression method. To further confirm the causal relationship between angina and gout incidence, a meta-analysis was conducted on the IVW results of the ukb-a-107 and bbj-a-57. Results: The odds ratios and 95% confidence intervals of the IVW, WME, and MR-Egger results of ukb-a-107 were (OR = 33.72; 95% CI: 2.07∼550.38), (OR = 57.94; 95% CI: 2.75∼1219.82), and (OR = 96.38; 95% CI: 0.6∼15556.93), respectively. The P values of IVW and WME were 0.014 and 0.014 (both <0.05), respectively, indicating that the development of angina pectoris was significantly associated with the incidence of gout. The odds ratios and 95% confidence intervals of the IVW, WME, and MR-Egger about bbj-a-57 were (OR = 1.20; 95% CI: 1.07∼1.34), (OR = 1.19; 95% CI: 1.02∼1.38), and (OR = 1.30; 95% CI; 1.06∼1.60), respectively. The P values of IVW, WME and MR-Egger were 0.001, 0.027 and 0.017 (all <0.05), respectively, indicating a significant correlation between angina and blood uric acid levels. Scatter plots of ukb-a-107 and bbj-a-57 showed that the causal association estimates of the IVW, MR-Egger, and weighted median methods were similar and that the MR results were accurate. Funnel plots and the MR-Egger intercept of ukb-a-107 and bbj-a-57 showed the absence of horizontal pleiotropy. The leave-out sensitivity analysis results of ukb-a-107 and bbj-a-57 are stable. The meta-analysis of IVW results for ukb-a-107 and bbj-a-57 showed (OR = 1.20; 95% CI: 1.07-1.34, P=0.02), confirming that gout characterized by high blood uric acid levels significantly increases the risk of angina attacks. Conclusions: This MR study found a clear causal relationship between angina pectoris and gout, which increases the risk of angina pectoris.

Snare technique failure in extracting an embolized coronary sinus reducer to the pulmonary artery.

We report the case of a 79-year-old male patient who benefited from the implantation of a coronary sinus reducer (CSR) (Reducer; Neovasc, Inc.) in the management of typical angina with mild exertion with optimal medical treatment.

Reduced Alcohol Consumption and Major Adverse Cardiovascular Events Among Individuals With Previously High Alcohol Consumption.

Importance: Cardiovascular benefits of mild to moderate alcohol consumption need to be validated in the context of behavioral changes. The benefits of reduced alcohol consumption among people who drink heavily across different subtypes of cardiovascular disease (CVD) are unclear. Objective: To investigate the association between reduced alcohol consumption and risk of major adverse cardiovascular events (MACEs) in individuals who drink heavily across different CVD subtypes. Design, Setting, and Participants: This cohort study analyzed data from the Korean National Health Insurance Service-Health Screening database and self-reported questionnaires. The nationally representative cohort comprised Korean citizens aged 40 to 79 years who had national health insurance coverage on December 31, 2002, and were included in the 2002 to 2003 National Health Screening Program. People who drank heavily who underwent serial health examinations over 2 consecutive periods (first period: 2005-2008; second period: 2009-2012) were included and analyzed between February and May 2023. Heavy drinking was defined as more than 4 drinks (56 g) per day or more than 14 drinks (196 g) per week for males and more than 3 drinks (42 g) per day or more than 7 drinks (98 g) per week for females. Exposures: Habitual change in heavy alcohol consumption during the second health examination period. People who drank heavily at baseline were categorized into 2 groups according to changes in alcohol consumption during the second health examination period as sustained heavy drinking or reduced drinking. Main Outcomes and Measures: The primary outcome was the occurrence of MACEs, a composite of nonfatal myocardial infarction or angina undergoing revascularization, any stroke accompanied by hospitalization, and all-cause death. Results: Of the 21 011 participants with heavy alcohol consumption at baseline (18 963 males [90.3%]; mean [SD] age, 56.08 [6.16] years) included in the study, 14 220 (67.7%) sustained heavy drinking, whereas 6791 (32.2%) shifted to mild to moderate drinking. During the follow-up of 162 378 person-years, the sustained heavy drinking group experienced a significantly higher incidence of MACEs than the reduced drinking group (817 vs 675 per 100 000 person-years; log-rank P = .003). Reduced alcohol consumption was associated with a 23% lower risk of MACEs compared with sustained heavy drinking (propensity score matching hazard ratio [PSM HR], 0.77; 95% CI, 0.67-0.88). These benefits were mostly accounted for by a significant reduction in the incidence of angina (PSM HR, 0.70; 95% CI, 0.51-0.97) and ischemic stroke (PSM HR, 0.66; 95% CI, 0.51-0.86). The preventive attributes of reduced alcohol intake were consistently observed across various subgroups of participants. Conclusions and Relevance: Results of this cohort study suggest that reducing alcohol consumption is associated with a decreased risk of future CVD, with the most pronounced benefits expected for angina and ischemic stroke.

The role of exercise-based cardiac rehabilitation after percutaneous coronary intervention in patients with coronary artery disease: a meta-analysis of randomised controlled trials.

BACKGROUND: this study was designed to analyse patient outcomes using a combination of PCI and exercise-based cardiac rehabilitation compared with PCI alone. METHODS: PCI can improve the survival rate of patients with coronary artery disease, but it can also cause vascular endothelial cell injury, thrombosis, and even restenosis. Early cardiac rehabilitation exercise is crucial for patients with coronary heart disease after PCI. Five databases were examined for randomised controlled trials involving early cardiac rehabilitation exercise and standard treatment in patients with coronary heart disease after PCI. The search period lasted from the creation of the database (2006) until December 2022. The outcomes including angina, arrhythmia, coronary restenosis, left ventricular ejection fraction, left ventricular end diastolic diameter, 6-min walk distance, total cholesterol, heart rate, systolic blood pressure and diastolic blood pressure. RevMan 5.3 was used to analyse the data, and the Cochrane Collaboration was used to assess the quality of evidence. RESULTS: A total of 1231 patients were enrolled in this study. Angina pectoris (RR = 0.24, 95% CI [0.10, 0.57], p = 0.001), Arrhythmia (RR = 0.17, 95% CI [0.05, 0.55], p = 0.003), Coronary artery restenosis (RR = 0.10, 95% CI [0.01, 0.76], p = 0.03). CONCLUSION: Exercise after PCI improves LVEF, enhances 6MWD, lowers HR and minimises the risk of angina, arrhythmia and coronary artery restenosis in CHD patients. Exercise had no discernible effect on LVEDD, TC, SBP, or DBP.

Optimal Medical Therapy for Stable Ischemic Heart Disease: Focus on Anti-anginal Therapy.

Chronic coronary disease (CCD) is a major cause of morbidity and mortality worldwide. The most common symptom of CCD is exertional angina pectoris, a discomfort in the chest that commonly occurs during activities of daily life. Patients are dismayed by recurring episodes of angina and seek medical help in preventing or minimizing episodes. Angina occurs when the coronary arteries are unable to supply sufficient blood flow to the cardiac muscle to meet the metabolic needs of the left ventricular myocardium. While lifestyle changes and aggressive risk factor modification play a critical role in the management of CCD, management of angina usually requires pharmacologic therapy. Medications such as beta-blockers, calcium channel blockers, nitrates, ranolazine, and others ultimately work to improve the mismatch between myocardial blood flow and metabolic demand. This manuscript briefly describes the pathophysiologic basis for symptoms of angina, and how currently available anti-anginal therapies contribute to preventing or minimize the occurrence of angina.

Early menopause is associated with abnormal diastolic function and poor clinical outcomes in women with suspected angina.

Early identification of women at high risk for cardiovascular diseases (CVD), with subsequent monitoring, will allow for improved clinical outcomes and generally better quality of life. This study aimed to identify the associations between early menopause, abnormal diastolic function, and clinical outcomes. This retrospective study included 795 menopausal women from is a nationwide, multicenter, registry of patients with suspected angina visiting outpatient clinic. The patients into two groups: early and normal menopause (menopausal age ≤ 45 and > 45 years, respectively). If participants met > 50% of the diastolic function criteria, they were classified as having normal diastolic function. Multivariable-adjusted Cox models were used to test associations between menopausal age and clinical outcomes including the incidence of major adverse cardiovascular events (MACE), over a median follow-up period of 771 days. Early menopause was associated with increased waist circumference (p = 0.001), diabetes prevalence (p = 0.003), obstructive coronary artery disease (p = 0.005), abnormal diastolic function (p = 0.003) and greater incidences of MACE, acute coronary syndrome, and hospitalization for heart failure. In patients with abnormal diastolic function, early menopause increased MACE risk significantly, with no significant difference in normal diastolic function. These findings highlight early menopause and abnormal diastolic function as being potential risk markers in women for midlife CVD events.

Neuromodulation of Cardiac Ischemic Pain: Role of the Autonomic Nervous System and Vasopressin.

Cardiac pain is an index of cardiac ischemia that helps the detection of cardiac hypoxia and adjustment of activity in the sufferer. Drivers and thresholds of cardiac pain markedly differ in different subjects and can oscillate in the same individual, showing a distinct circadian rhythmicity and clinical picture. In patients with syndrome X or silent ischemia, cardiac pain intensity may cause neurogenic stress that potentiates the cardiac work and intensifies the cardiac hypoxia and discomfort of the patient. The reasons for individual differences in cardiac pain sensation are not fully understood. Thus far, most attention has been focused on inappropriate regulation of the heart by the autonomic nervous system, autacoids, and cardiovascular hormones. Herein, we summarize evidence showing that the autonomic nervous system regulates cardiac pain sensation in cooperation with vasopressin (AVP). AVP is an essential analgesic compound and it exerts its antinociceptive function through actions in the brain (the periaqueductal gray, caudate nucleus, nucleus raphe magnus), spinal cord, and heart and coronary vessels. Vasopressin acts directly by means of V1 and V2 receptors as well as through multiple interactions with the autonomic nervous system and cardiovascular hormones, in particular, angiotensin II and endothelin. The pain regulatory effects of the autonomic nervous system and vasopressin are significantly impaired in cardiovascular diseases.

Safety of helicopter transport in patients with acute coronary syndrome.

BACKGROUND: ST-elevation myocardial infarction (STEMI) systems of care have reduced inter-hospital transfer times and facilitated timely reperfusion goals. Helicopters may be an option when land transportation is not feasible; however, the safety of air transport in patients with acute coronary syndrome (ACS) is a factor to consider. OBJETIVES: The aim of this study was to evaluate the safety of helicopter transport for patients with ACS. METHODS: Prospective, observational, and descriptive study including patients diagnosed with ACS within the STEMI network of a metropolitan city transferred by helicopter to a large cardiovascular center to undergo percutaneous coronary intervention. The primary outcome of the study was the incidence of air-travel-related complications defined as IV dislodgement, hypoxia, arrhythmia, angina, anxiety, bleeding, and hypothermia. Secondary outcomes included the individual components of the primary outcome. RESULTS: A total of 106 patients were included in the study; the mean age was 54 years and 84.9% were male. The most frequent diagnosis was STEMI after successful fibrinolysis (51.8%), followed by STEMI with failed fibrinolysis (23.7%) and non-reperfused STEMI (9.4%). Five patients (4.7%) developed at least one complication: IV dislodgement (1.8%) and hypoxemia (1.8%) in two patients and an episode of angina during flight (0.9%). A flight altitude of > 10,000 ft was not associated with complications. CONCLUSIONS: The results of this study suggest that helicopter transportation is safe in patients undergoing acute coronary syndrome, despite the altitude of a metropolitan area.

ANTECEDENTES: Los sistemas de atención de IAMCEST han reducido los tiempos de transferencia interhospitalaria y han facilitado las metas de reperfusión oportuna. Los helicópteros pueden ser una opción cuando el transporte terrestre no es factible; sin embargo, la seguridad del transporte aéreo en pacientes con síndrome coronario agudo (SICA) es un factor a considerar. OBJETIVOS: Evaluar la seguridad del transporte en helicóptero para pacientes con SICA. MÉTODOS: Estudio prospectivo, observacional, descriptivo. Se incluyeron pacientes con diagnóstico de SICA dentro de la red IAMCEST en metrópolis extensa, trasladados en helicóptero a un centro cardiovascular. El resultado primario del estudio fue la incidencia de complicaciones relacionadas con los viajes aéreos definidas cómo desalojo de catéter intravenoso, hipoxia, arritmia, angina, ansiedad, sangrado e hipotermia. RESULTADOS: Total de 106 pacientes; la edad media fue de 54 años y 84,9% eran hombres. La altitud media de vuelo fue de 10,100 pies y la distancia media de vuelo fue de 50,0 km. El diagnóstico más frecuente fue IAMCEST tras fibrinolisis exitosa (51,8%), seguido de IAMCEST con fibrinolisis fallida (23,7%). Cinco pacientes (4,7%) desarrollaron una complicación: desalojo IV (1,8%) e hipoxemia (1,8%) en dos pacientes y un episodio de angina durante el vuelo (0,9%). Una altitud de vuelo mayor de 10,000 pies no se asoció a complicaciones. CONCLUSIONES: Los resultados de este estudio sugieren que el transporte en helicóptero es seguro en pacientes con SICA, incluso en altitudes > 10,000 pies.

Genetically Predicted Apolipoprotein E Levels with the Risk of Panvascular Diseases: A Mendelian Randomization Study.

The aim of this study was to comprehensively assess the causal relationship between the overall genetic effect of circulating ApoE levels and panvascular lesions using newer genome-wide association data and two-sample bidirectional Mendelian randomization (MR) analysis. Two-way MR using single-nucleotide polymorphisms of circulating ApoE as instrumental variables was performed using the highest-priority Genome-wide association study (GWAS) data, with factor-adjusted and data-corrected statistics, to estimate causal associations between circulating ApoE levels and 10 pan-vascular diseases in > 500,000 UK Biobank participants, > 400,000 participants of Finnish ancestry, and numerous participants in a consortium of predominantly European ancestry. Meta-analysis was conducted to assess positive results. After correcting for statistical results, elevated circulating ApoE levels were shown to have a significant protective effect against Cerebral ischemia (CI) [IVW odds ratio (OR) 0.888, 95% Confidence Interval (CI): 0.823-0.958, p = 2.3 × 10-3], Coronary heart disease [IVW OR 0.950,95% CI: 0.924-0.976, p = 2.0 × 10-4] had a significant protective effect and potentially suggestive protective causality against Angina pectoris [IVW odds ratio (OR) 0.961, 95%CI: 0.931-0.991, p = 1.1 × 10-2]. There was a potential causal effect for increased risk of Heart failure (HF) [IVW ratio (OR) 1.040, 95%CI: 1.006-1.060, p = 1.8 × 10-2]. (Bonferroni threshold p < 0.0026, PFDR < 0.05) Reverse MR analysis did not reveal significant evidence of a causal effect of PVD on changes in circulating ApoE levels. Meta-analysis increases reliability of results. Elevated circulating ApoE levels were particularly associated with an increased risk of heart failure. Elevated ApoE levels reduce the risk of cerebral ischemia, coronary heart disease, and angina pectoris, reflecting a protective effect. The possible pathophysiological role of circulating ApoE levels in the development of panvascular disease is emphasized.

Coronary Vasomotor Dysfunction Is Associated With Cardiovascular Events in Patients With Nonobstructive Coronary Artery Disease.

BACKGROUND: Coronary vasomotor dysfunction (CVDys) can be comprehensively classified on the basis of anatomy and functional mechanisms. OBJECTIVES: The aim of this study was to evaluate the association between different CVDys phenotypes and outcomes in patients with angina and nonobstructive coronary artery disease (ANOCA). METHODS: Patients with ANOCA who underwent coronary reactivity testing using an intracoronary Doppler guidewire to assess microvascular and epicardial coronary endothelium-dependent and endothelium-independent function were enrolled. Endothelium-dependent microvascular and epicardial coronary dysfunction were defined as a <50% change in coronary blood flow in response to intracoronary acetylcholine (Ach) infusion and a <-20% change in coronary artery diameter in response to Ach. Endothelium-independent microvascular and epicardial coronary dysfunction were defined as coronary flow reserve < 2.5 during adenosine-induced hyperemia and change in cross-sectional area in response to intracoronary nitroglycerin administration < 20%. Major adverse cardiac and cerebrovascular events (cardiovascular death, nonfatal MI, heart failure, stroke, and late revascularization) served as clinical outcomes. RESULTS: Among the 1,196 patients with ANOCA, the prevalence of CVDys was 24.5% and 51.8% among those with endothelium-independent and endothelium-dependent microvascular dysfunction, respectively, and 47.4% and 25.4% among those with endothelium-independent and endothelium-dependent epicardial coronary dysfunction, respectively. During 6.3 years (Q1-Q3: 2.5-12.9 years) of follow-up, patients with endothelium-dependent microvascular dysfunction, endothelium-dependent epicardial coronary dysfunction, or endothelium-independent microvascular dysfunction showed significantly higher event rates compared with those without (19.5% vs 12.0% [P < 0.001], 19.7% vs 14.6% [P = 0.038] and 22.2% vs 13.8% [P = 0.001], respectively). Coronary flow reserve (HR: 0.757; 95% CI: 0.604-0.957) and percentage change in coronary blood flow in response to Ach infusion (HR: 0.998; 95% CI: 0.996-0.999) remained significant predictors of major adverse cardiac and cerebrovascular event after adjustment for conventional risk factors. CONCLUSIONS: CVDys phenotype is differentially associated with worse outcomes, and endothelium-dependent and endothelium-independent microvascular function provide independent prognostic information in patients with ANOCA.

Long-term prognostic factors for cardiovascular events in patients with chest pain without diabetes mellitus nor significant coronary stenosis.

Chest pain is the most common symptom of coronary artery disease (CAD) and diabetes mellitus (DM) is a well-known single strongest risk factor for cardiovascular diseases. Thus, the impact of CAD nor DM on long-term clinical effects is reported widely, but the prognostic factors of non-DM patients presenting with chest pain without significant CAD are limited. A total of 1,046 patients with chest pain without DM and significant CAD who underwent coronary angiography (CAG) and acetylcholine (ACH) provocation tests were finally enrolled. Propensity score matching and multivariate Cox-proportional hazard ratio analysis were performed to adjust for baseline potential confounders. Major adverse cardiac and cerebrovascular events (MACCE) were defined as the composite of total death, myocardial infarction (MI), revascularization, stroke, and recurrent angina. This study aimed to evaluate the long-term prognostic factors for MACCE in patients with chest pain without DM and CAD up to 5 years. Coronary artery spasm (CAS) was the most common cause of chest pain. However, long-term MACCE of CAS was not worse than those of patients with chest pain without CAS when patients with CAS had subsequent optimal antianginal medication therapy. However, a recurrent chest pain remains a problem even with continuous antianginal medication therapy. Up to 5 years, the incidence of MACCE was in 7.3%, including recurrent angina 6.9%. Dyslipidemia (HR: 2.010, 95% CI 1.166-3.466, P = 0.012), mild-moderate (30-70%) coronary stenosis (HR: 2.369, 95% CI 1.118-5.018, P = 0.024), the use of aspirin (HR: 2.885, 95% CI 1.588-5.238, P < 0.001), and the use of nitrates (HR: 1.938, 95% CI 1.094-3.433, P = 0.023) were independent risk factors for MACCE. Among the patients with chest pain without DM and significant CAD, the incidence of MACE were rare, but recurrent angina was still a challenging problem who had treated with antianginal medications.