BACKGROUND-Microvascular dysfunction (MVD) is a potential cause of chest pain in younger individuals. We hypothesized that non-elderly patients referred for computed tomography coronary angiography (CTA) but without significant stenosis would have a high prevalence of MVD by myocardial contrast echocardiography (MCE). Secondary aims were to test whether the presence of non-obstructive CAD or reduced brachial flow-mediated dilation (FMD) predicted MVD. METHODS-Subjects ≤60 years-of-age undergoing CTA were recruited if they had either no evidence of coronary plaque, or evidence of mild CAD (<50% stenosis) and at least one high-risk plaque feature. Subjects underwent quantitative MCE perfusion imaging at rest and during regadenoson vasodilator stress. Microvascular dysfunction was defined by global or segmental delay of microvascular refill (≥2 seconds) during regadenoson. FMD of the brachial artery was also performed.
Cardiovascular biomarkers started as tools to aid with specific medical diagnoses, but are now being used broadly for screening, prognosis and monitoring of multiple diseases. Novel markers that reflect important pathophysiologic pathways are emerging regularly, although each new set of markers introduced raises many questions on how best to utilize them to improve patient outcomes. One promising approach for getting the most out of cardiovascular biomarkers is to combine multiple markers together into a multimarker panel. When each marker represents a distinct pathophysiologic pathway, the combined panel has advantages over individual biomarkers and may be useful when used in specific clinical scenarios for assessing risk, improving diagnosis or directing individualized therapy. This perspective article highlights several of the most promising biomarkers and strategies for achieving improved cardiovascular risk assessment for primary prevention of cardiovascular disease via multimarker panels.
Coronary microvascular dysfunction (MVD) is a syndrome of abnormal regulation of vascular tone, particularly during increased metabolic demand. While there are several risk factors for MVD, some of which are similar to those for coronary artery disease (CAD), the cause of MVD is not understood. We hypothesized that MVD in symptomatic non-elderly subjects would be characterized by specific lipidomic profiles. Subjects (n = 20) aged 35–60 years and referred for computed tomography coronary angiography (CTA) for chest pain but who lacked obstructive CAD (>50% stenosis), underwent quantitative regadenoson stress-rest myocardial contrast echocardiography (MCE) perfusion imaging for MVD assessment. The presence of MVD defined by kinetic analysis of MCE data was correlated with lipidomic profiles in plasma measured by liquid chromatography and high-resolution mass spectrometry. Nine of twenty subjects had evidence of MVD, defined by reduced hyperemic perfusion versus other subjects (beta-value 1.62 ± 0.44 vs. 2.63 ± 0.99 s−1, p = 0.009). Neither the presence of high-risk but non-obstructive CAD on CTA, nor CAD risk factors were different for those with versus without MVD. Lipidomic analysis revealed that patients with MVD had lower concentrations of long-carbon chain triacylglycerols and diacylglycerols, and higher concentrations of short-chain triacylglycerols. The diacylglycerol containing stearic and linoleic acid classified all participants correctly. We conclude that specific lipidomic plasma profiles occur in MVD involving saturated long-chain fatty acid-containing acylglycerols that are distinctly different from those in non-obstructive CAD. These patterns could be used to better characterize the pathobiology and potential treatments for this condition.
ObjectivesIschemia with no obstructive coronary artery disease (INOCA) is a risk factor for major adverse cardiovascular events and is characterized by abnormal coronary microvascular tone. In patients with INOCA, adverse cardiovascular events most commonly occur in the morning compared to other times of the day and night.Materials and methodsWe tested whether coronary microvascular function varies diurnally with attenuation in the morning in patients with symptomatic coronary artery disease without significant (>50%) epicardial stenosis. We evaluated data from 17 patients studied in the AM (700–1159 h) and 11 patients in the PM (1200–1800 h). Coronary microvascular function was measured using perfusion contrast imaging at rest and after infusion of intravenous regadenoson. We calculated microvascular flow reserve as the ratio of hyperemic to resting flow. Along with independent sample t-tests, we performed bootstrapping procedures to test mean differences between AM and PM groups, using the bias-corrected and accelerated method with 5,000 bootstrapped samples.Results and conclusionThe AM and PM groups were matched for demographic and existing risk factors. Coronary microvascular flow reserve was ∼33% higher in the AM compared to the PM (P = 0.025, BCa 95% CI [0.25, 1.64]; Hedge’s g = 0.89, 95% CI [0.11, 1.66]) as a result of significantly lower resting flow (∼50%) in the AM compared to the PM (P = 0.03, MDiff = −56.65, BCa 95% CI [−118.59, −2.12]; Hedge’s g = −0.86, 95% CI [−1.60, −0.06]). Our observations are of clinical value and can influence diagnosis and treatment in the clinic based on the time of day of measurements.
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