Association of diabetes with coronary artery calcium in South Asian adults and other race/ethnic groups: The multi-ethnic study of atherosclerosis and the mediators of atherosclerosis in South Asians living in America study.

PURPOSE: South Asian (SA) persons have increased risks for diabetes mellitus (DM) and atherosclerotic cardiovascular disease (ASCVD). We examined whether the association of DM with subclinical atherosclerosis assessed by coronary artery calcium (CAC) differs in SA versus other ethnic groups. METHODS: We studied adults from the Multi-Ethnic Study of Atherosclerosis and the Mediators of Atherosclerosis in South Asians Living in America studies without ASCVD. CAC was examined among those normoglycemic, pre-DM and DM. Logistic regression examined pre-DM and DM with the odds of any CAC > 0 and CAC ≥ 100. RESULTS: Among 7562 participants, CAC > 0 and CAC ≥ 100 in those with DM was highest in non-Hispanic White (NHW) (80% and 48%) and SA (72% and 41%) persons. Adjusted Ln (CAC + 1) was highest in NHW (3.68 ± 0.21) and SA (3.60 ± 0.23) (p < .01) DM patients. SA and NHW adults with DM (vs normoglycemic) had highest odds of CAC > 0 (2.13 and 2.27, respectively, p < .01). For CAC ≥ 100, SA and Chinese adults had the highest odds (2.28 and 2.27, respectively, p < .01). Fasting glucose and glycated hemoglobin were most strongly associated with CAC among SA. CONCLUSIONS: Diabetes mellitus most strongly relates to any CAC in SA and NHW adults and CAC ≥ 100 in SA and Chinese adults, helping to explain the relation of DM with ASCVD in these populations.

Case report: a breathtaking complication after ablation-using multi-modal imaging for timely diagnosis of acquired pulmonary vein stenosis and its implication for effective management.

Background: Acquired pulmonary vein stenosis (PVS) is a rare, but serious, complication that can develop after treatment with ablations for atrial fibrillation. Prompt diagnosis is difficult because it can often present similarly to other pulmonary disease processes. Case summary: We describe a 62-year-old female with history of persistent symptomatic atrial fibrillation that resolved status post two radio-frequency ablations who presents with ongoing dyspnoea, productive cough, pleuritic chest pain, and haemoptysis over multiple admissions. She was misdiagnosed with recurrent pneumonias and pulmonary embolism that failed to improve her symptoms. She was referred to our centre for further evaluation finding severe stenosis in the left superior pulmonary vein with complete obliteration of the left inferior pulmonary vein on computed tomography scan. Multi-modal imaging including an echocardiogram and pulmonary angiogram was used to confirm the diagnosis. Percutaneous intervention with transvenous pulmonary vein venoplasty with pulmonary vein stenting of the left upper pulmonary vein was offered which resolved the patient's aforementioned symptoms. Conclusion: Prompt diagnosis of acquired pulmonary vein stenosis is critical to plan for effective management. Our case highlights the need to consider PVS with a high index of clinical suspicion when a patient's medical history is significant for a prior history of ablation. We also review the use of multi-modal imaging to diagnose and plan for effective management with percutaneous intervention.

Novel biomarker panel measuring endothelial injury identifies patients at risk of coronary artery syndrome and discordance with low-density lipoprotein cholesterol.

BACKGROUND: Individuals with no history of coronary artery disease can develop acute coronary syndrome (ACS), often in the absence of major risk factors including low-density lipoprotein cholesterol (LDL-C). We identified risk factors and biomarkers that can help identify those at discordantly high risk of ACS with normal LDL-C using a novel validated coronary artery disease predictive algorithm (CADPA) incorporating biomarkers of endothelial injury. METHODS: Five-year predicted ACS risk was calculated for 6392 persons using CADPA. Persons were classified as low (<3.5%), intermediate (3.5-<7.5%) or high (≥7.5%) CADPA risk and by LDL-C levels <130 mg/dL (low) and ≥130 mg/dL (high) and whether in the discordantly low LDL-C (but high CADPA risk) or high LDL-C (but low/intermediate CADPA risk) group. Multiple logistic regression identified risk factors and biomarkers that predicted discordance. RESULTS: 31% were classified as low (<3.5%), 27% at intermediate (3.5-<7.5%) and 42% were at high risk (≥7.5%). 28% of subjects were identified in the low LDL discordant risk group (LDL-C< 130 mg/dL but 5-year CADPA predicted risk ≥7.5%) and 19% in the high LDL discordant risk group (LDL-C ≥ 130 mg/dL but 5-year CADPA risk of <7.5%). Diabetes (odds ratio [OR], 2.84 [2.21-3.66]), male sex (OR, 2.83 [2.40-3.35]), family history (OR, 2.23 [1.88-2.64]) and active smoking (OR, 1.99 [1.50-2.62]) predicted low LDL risk discordance more than other risk factors (all P < 0.01). Increased serum soluble FAS, hemoglobin A1c and interleukin-16 were the biomarkers most independently associated with increased risk. CONCLUSIONS: Discordance between LDL-C levels and ACS risk is common. Males with diabetes and a family history of myocardial infarction who are actively smoking may be at highest risk of developing ACS despite controlled LDL-C. Future studies should examine whether using the CADPA can help identify individuals that could benefit from earlier targeting of risk factor modification for the prevention of ACS.

Clinical Outcomes Data for Instantaneous Wave-Free Ratio-Guided Percutaneous Coronary Intervention.

Instantaneous wave-free ratio (iFR) is a vasodilator-free index of coronary blood flow used for revascularization decision-making. iFR-based revascularization also had a decreased rate of adverse effects from vasodilators, shorter procedure times, and lower revascularization rates. iFR-pullback predicts post-percutaneous coronary intervention physiologic outcomes in tandem and diffuse coronary lesions. iFR may be particularly useful in patients with potential adenosine resistance, contraindications to adenosine, and multivessel or serial lesions. iFR is a useful tool both with and without fractional-flow reserve for revascularization planning.

Usefulness of a Coronary Artery Disease Predictive Algorithm to Predict Global Risk for Cardiovascular Disease and Acute Coronary Syndrome.

Traditional global risk assessment for cardiovascular disease fails to identify a significant percentage of the population initially classified at low or intermediate risk of cardiovascular disease that are actually at high risk for acute coronary syndrome (ACS). We examined a coronary artery disease predictive algorithm (CADPA) that includes 9 biomarkers involved in the pathogenesis of atherosclerosis initiated by endothelial damage and repair (hepatocyte growth factor, soluble FAS, Fas ligand, eotaxin, cutaneous T cell-attracting chemokine, monocyte chemotactic protein-3, interleukin-16, hemoglobin A1c, high-density lipoprotein-cholesterol), in addition to age, gender, diabetes, and family history of myocardial infarction that more accurately predicts 5-year risk of ACS to identify the patient population at discordantly high risk. We found that 34% of patients at low risk by global risk assessment and 72% of patients at intermediate risk by global risk assessment were actually at discordantly high risk for ACS. This patient population was disproportionately male and older in age. The biomarkers (per standard deviation) that most predicted the odds (95% confidence levels) of discordance were interleukin-16 (2.59 [2.21 to 3.03]), Fas Ligand (0.50 [0.43 to 0.57]), hepatocyte growth factor (1.72 [1.50 to 1.98]), soluble FAS (2.19 [1.86 to 2.58]), cutaneous T cell-attracting chemokine (0.46 [0.40 to 0.53]), and eotaxin (1.78 [1.56 to 2.03]), in addition to age, HbA1c, low-density lipoprotein-cholesterol, and glycated hemoglobin. In conclusion, although future prospective study validation is needed to establish a causal relation between CADPA and cardiovascular events, our study defines a patient population considered low to intermediate risk by conventional clinical evaluation, but who is at discordantly high risk indicated by the endothelial injury serum biomarker algorithm CADPA and may benefit from further evaluation and medical management.

Intermediary metabolism and fatty acid oxidation: novel targets of electron transport chain-driven injury during ischemia and reperfusion.

Cardiac ischemia-reperfusion (I/R) damages the electron transport chain (ETC), causing mitochondrial and cardiomyocyte injury. Reversible blockade of the ETC at complex I during ischemia protects the ETC and decreases cardiac injury. In the present study, we used an unbiased proteomic approach to analyze the extent of ETC-driven mitochondrial injury during I/R. Isolated-perfused mouse (C57BL/6) hearts underwent 25-min global ischemia (37°C) and 30-min reperfusion. In treated hearts, amobarbital (2 mM) was given for 1 min before ischemia to rapidly and reversibly block the ETC at complex I. Mitochondria were isolated at the end of reperfusion and subjected to unbiased proteomic analysis using tryptic digestion followed by liquid chromatography-mass spectrometry with isotope tags for relative and absolute quantification. Amobarbital treatment decreased cardiac injury and protected respiration. I/R decreased the content ( P < 0.05) of multiple mitochondrial matrix enzymes involved in intermediary metabolism compared with the time control. The contents of several enzymes in fatty acid oxidation were decreased compared with the time control. Blockade of ETC during ischemia largely prevented the decreases. Thus, after I/R, not only the ETC but also multiple pathways of intermediary metabolism sustain damage initiated by the ETC. If these damaged mitochondria persist in the myocyte, they remain a potent stimulus for ongoing injury and the transition to cardiomyopathy during prolonged reperfusion. Modulation of ETC function during early reperfusion is a key strategy to preserve mitochondrial metabolism and to decrease persistent mitochondria-driven injury during longer periods of reperfusion that predispose to ventricular dysfunction and heart failure. NEW & NOTEWORTHY Ischemia-reperfusion (I/R) damages mitochondria, which could be protected by reversible blockade of the electron transport chain (ETC). Unbiased proteomics with isotope tags for relative and absolute quantification analyzed mitochondrial damage during I/R and found that multiple enzymes in the tricarboxylic acid cycle, fatty acid oxidation, and ETC decreased, which could be prevented by ETC blockade. Strategic ETC modulation can reduce mitochondrial damage and cardiac injury.

Speech perception in older hearing impaired listeners: benefits of perceptual training.

Hearing aids (HAs) only partially restore the ability of older hearing impaired (OHI) listeners to understand speech in noise, due in large part to persistent deficits in consonant identification. Here, we investigated whether adaptive perceptual training would improve consonant-identification in noise in sixteen aided OHI listeners who underwent 40 hours of computer-based training in their homes. Listeners identified 20 onset and 20 coda consonants in 9,600 consonant-vowel-consonant (CVC) syllables containing different vowels (/ɑ/, /i/, or /u/) and spoken by four different talkers. Consonants were presented at three consonant-specific signal-to-noise ratios (SNRs) spanning a 12 dB range. Noise levels were adjusted over training sessions based on d' measures. Listeners were tested before and after training to measure (1) changes in consonant-identification thresholds using syllables spoken by familiar and unfamiliar talkers, and (2) sentence reception thresholds (SeRTs) using two different sentence tests. Consonant-identification thresholds improved gradually during training. Laboratory tests of d' thresholds showed an average improvement of 9.1 dB, with 94% of listeners showing statistically significant training benefit. Training normalized consonant confusions and improved the thresholds of some consonants into the normal range. Benefits were equivalent for onset and coda consonants, syllables containing different vowels, and syllables presented at different SNRs. Greater training benefits were found for hard-to-identify consonants and for consonants spoken by familiar than unfamiliar talkers. SeRTs, tested with simple sentences, showed less elevation than consonant-identification thresholds prior to training and failed to show significant training benefit, although SeRT improvements did correlate with improvements in consonant thresholds. We argue that the lack of SeRT improvement reflects the dominant role of top-down semantic processing in processing simple sentences and that greater transfer of benefit would be evident in the comprehension of more unpredictable speech material.

Aided and unaided speech perception by older hearing impaired listeners.

The most common complaint of older hearing impaired (OHI) listeners is difficulty understanding speech in the presence of noise. However, tests of consonant-identification and sentence reception threshold (SeRT) provide different perspectives on the magnitude of impairment. Here we quantified speech perception difficulties in 24 OHI listeners in unaided and aided conditions by analyzing (1) consonant-identification thresholds and consonant confusions for 20 onset and 20 coda consonants in consonant-vowel-consonant (CVC) syllables presented at consonant-specific signal-to-noise (SNR) levels, and (2) SeRTs obtained with the Quick Speech in Noise Test (QSIN) and the Hearing in Noise Test (HINT). Compared to older normal hearing (ONH) listeners, nearly all unaided OHI listeners showed abnormal consonant-identification thresholds, abnormal consonant confusions, and reduced psychometric function slopes. Average elevations in consonant-identification thresholds exceeded 35 dB, correlated strongly with impairments in mid-frequency hearing, and were greater for hard-to-identify consonants. Advanced digital hearing aids (HAs) improved average consonant-identification thresholds by more than 17 dB, with significant HA benefit seen in 83% of OHI listeners. HAs partially normalized consonant-identification thresholds, reduced abnormal consonant confusions, and increased the slope of psychometric functions. Unaided OHI listeners showed much smaller elevations in SeRTs (mean 6.9 dB) than in consonant-identification thresholds and SeRTs in unaided listening conditions correlated strongly (r = 0.91) with identification thresholds of easily identified consonants. HAs produced minimal SeRT benefit (2.0 dB), with only 38% of OHI listeners showing significant improvement. HA benefit on SeRTs was accurately predicted (r = 0.86) by HA benefit on easily identified consonants. Consonant-identification tests can accurately predict sentence processing deficits and HA benefit in OHI listeners.