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Elevated renalase levels in patients with acute coronary microvascular dysfunction - A possible biomarker for ischemia.

ABSTRACT: AIMS:We explored the relationship between inflammation, renalase an anti-inflammatory protein, and acute chest pain with coronary microvascular dysfunction (CMD). METHODS AND RESULTS:We used cardiac Rb-82 PET/CT imaging to diagnose coronary artery disease (CAD/CALC) (defect or coronary calcification) and CMD (depressed coronary flow reserve without CAD) in patients with chest pain in an emergency department (ED). Blood samples were collected pre-imaging within 24?h of ED presentation and were analyzed for renalase and inflammatory markers including C-reactive protein, interleukins, interferon gamma, tumor necrosis factor, vascular endothelial growth factor, and metalloproteinases. Exclusions were age ?30?years, myocardial infarction, hemodynamic instability, hypertensive crisis, heart failure or dialysis. Between 6/2014 and 11/2015, 80 patients undergoing PET/CT provided blood and were categorized as normal (18%), CAD/CALC (27%) and CMD (55%). Median renalase values were highest in patients with CMD (5503?ng/ml; IQR 3070) compared to patients with normal flows (4266?ng/ml; IQR 1503; p?=?0.02) or CAD/CALC (4069?ng/ml IQR 1850; p?=?0.004). CMD patients had similar median values for inflammatory markers as normal patients (p?>?0.05). Renalase remained an independent predictor of CMD (OR 1.34; 95% CI?=?1.1-1.7, per 1000?ng/ml) after adjustment for smoking, family history, obesity and Framingham risk score. In a model for CMD diagnosis with Framingham risk score, typical angina history and CRP, renalase improved discrimination from C-statistic?=?0.60 (95% CI 0.47, 0.73) to 0.70 (95% CI, 0.59-0.82). CONCLUSION:We found elevated renalase in response to ischemia from acute CMD. Its role as a biomarker needs validation in larger trials.

SUBMITTER: Safdar B

PROVIDER: S-EPMC6482834 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Elevated renalase levels in patients with acute coronary microvascular dysfunction - A possible biomarker for ischemia.

Safdar Basmah B Guo Xiaojia X Johnson Caitlin C D'Onofrio Gail G Dziura James J Sinusas Albert J AJ Testani Jeffrey J Rao Veena V Desir Gary G

International journal of cardiology 20190102

<h4>Aims</h4>We explored the relationship between inflammation, renalase an anti-inflammatory protein, and acute chest pain with coronary microvascular dysfunction (CMD).<h4>Methods and results</h4>We used cardiac Rb-82 PET/CT imaging to diagnose coronary artery disease (CAD/CALC) (defect or coronary calcification) and CMD (depressed coronary flow reserve without CAD) in patients with chest pain in an emergency department (ED). Blood samples were collected pre-imaging within 24 h of ED presentat ...[more]

PMID: 30630613

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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.

Project description:Background Elevated levels of serum homocysteine, via impaired nitric oxide production, and coronary microvascular dysfunction are associated with increased risk of major adverse cardiovascular events. However, whether serum homocysteine levels and coronary microvascular endothelial dysfunction (CMED) are linked remains unknown. Methods and Results This study included 1418 patients with chest pain or an abnormal functional stress test and with nonobstructive coronary artery disease (<40% angiographic stenosis), who underwent CMED evaluation with functional angiography and had serum homocysteine levels measured. Patients were classified as having normal microvascular function versus CMED. Patients in the CMED group (n=743; 52%) had higher mean age (52.1±12.2 versus 50.0±12.4 years; P<0.0001), higher body mass index (29.1 [25.0-32.8] versus 27.5 [24.2-32.4]; P=0.001), diabetes mellitus (12.5% versus 9.4%; P=0.03), and fewer women (63.5% versus 68.7%; P=0.04) compared with patients in the normal microvascular function group. However, they had lower rates of smoking history, and mildly lower low-density lipoprotein cholesterol levels. Serum homocysteine levels were significantly higher in patients with CMED, and the highest quartile of serum homocysteine level (>9 µmol/L) was an independent predictor of CMED (odds ratio, 1.34 [95% CI, 1.03-1.75]; P=0.03) after adjustment for age; sex; body mass index; chronic kidney disease (CKD); diabetes mellitus; smoking exposure; low-density lipoprotein cholesterol; high-density lipoprotein cholesterol and triglycerides; and aspirin, statin, and B vitamin use. Conclusions Patients with CMED have significantly higher levels of serum homocysteine. Elevated serum homocysteine levels were associated with a significantly increased odds of an invasive diagnosis of CMED. The current study supports a potential role for homocysteine for diagnosis and target treatment in the patients with early coronary atherosclerosis.

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Elevated renalase levels in patients with acute coronary microvascular dysfunction - A possible biomarker for ischemia.

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Elevated renalase levels in patients with acute coronary microvascular dysfunction - A possible biomarker for ischemia.

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