Jaskanwal D. Sara

Patients With Coronary Endothelial Dysfunction Have Impaired Cholesterol Efflux Capacity and Reduced HDL Particle Concentration

RATIONALE Coronary endothelial dysfunction (ED)-an early marker of atherosclerosis-increases the risk of cardiovascular events. OBJECTIVE We tested the hypothesis that cholesterol efflux capacity and high-density lipoprotein (HDL) particle concentration predict coronary ED better than HDL-cholesterol (HDL-C). METHODS AND RESULTS We studied 80 subjects with nonobstructive (<30% stenosis) coronary artery disease. ED was defined as <50% change in coronary blood flow in response to intracoronary infusions of acetylcholine during diagnostic coronary angiography. Cholesterol efflux capacity and HDL particle concentration (HDL-PIMA) were assessed with validated assays. Cholesterol efflux capacity and HDL-PIMA were both strong, inverse predictors of ED (P<0.001 and 0.005, respectively). In contrast, HDL-C and other traditional lipid risk factors did not differ significantly between control and ED subjects. Large HDL particles were markedly decreased in ED subjects (33%; P=0.005). After correction for HDL-C, both efflux capacity and HDL-PIMA remained significant predictors of ED status. HDL-PIMA explained cholesterol efflux capacity more effectively than HDL-C (r=0.54 and 0.36, respectively). The efflux capacities of isolated HDL and serum HDL correlated strongly (r=0.49). CONCLUSIONS Cholesterol efflux capacity and HDL-PIMA are reduced in subjects with coronary ED, independently of HDL-C. Alterations in HDL-PIMA and HDL itself account for a much larger fraction of the variation in cholesterol efflux capacity than does HDL-C. A selective decrease in large HDL particles may contribute to impaired cholesterol efflux capacity in ED subjects. These observations support a role for HDL size, concentration, and function as markers-and perhaps mediators-of coronary atherosclerosis in humans.

Clinical outcomes of patients with hypothyroidism undergoing percutaneous coronary intervention

AIMS The aim of this study was to investigate the association between hypothyroidism and major adverse cardiovascular and cerebral events (MACCE) in patients undergoing percutaneous coronary intervention (PCI). METHODS AND RESULTS Two thousand four hundred and thirty patients who underwent PCI were included. Subjects were divided into two groups: hypothyroidism (n = 686) defined either as a history of hypothyroidism or thyroid-stimulating hormone (TSH) ≥5.0 mU/mL, and euthyroidism (n = 1744) defined as no history of hypothyroidism and/or 0.3 mU/mL ≤ TSH < 5.0 mU/mL. Patients with hypothyroidism were further categorized as untreated (n = 193), or those taking thyroid replacement therapy (TRT) with adequate replacement (0.3 mU/mL ≤ TSH < 5.0 mU/mL, n = 175) or inadequate replacement (TSH ≥ 5.0 mU/mL, n = 318). Adjusted hazard ratios (HRs) were calculated using Cox proportional hazards models. Median follow-up was 3.0 years (interquartile range, 0.5-7.0). After adjustment for covariates, the risk of MACCE and its constituent parts was higher in patients with hypothyroidism compared with those with euthyroidism (MACCE: HR: 1.28, P = 0.0001; myocardial infarction (MI): HR: 1.25, P = 0.037; heart failure: HR: 1.46, P = 0.004; revascularization: HR: 1.26, P = 0.0008; stroke: HR: 1.62, P = 0.04). Compared with untreated patients or those with inadequate replacement, adequately treated hypothyroid patients had a lower risk of MACCE (HR: 0.69, P = 0.005; HR: 0.78, P = 0.045), cardiac death (HR: 0.43, P = 0.008), MI (HR: 0.50, P = 0.0004; HR: 0.60, P = 0.02), and heart failure (HR: 0.50, P = 0.02; HR: 0.52, P = 0.017). CONCLUSION Hypothyroidism is associated with a higher incidence of MACCE compared with euthyroidism in patients undergoing PCI. Maintaining adequate control on TRT is beneficial in preventing MACCE.

Hypothyroidism Is Associated With Coronary Endothelial Dysfunction in Women.

Background Hypothyroidism is associated with an increased risk of coronary artery disease, beyond that which can be explained by its association with conventional cardiovascular risk factors. Coronary endothelial dysfunction precedes atherosclerosis, has been linked to adverse cardiovascular events, and may account for some of the increased risk in patients with hypothyroidism. The aim of this study was to determine whether there is an association between epicardial and microvascular coronary endothelial dysfunction and hypothyroidism. Methods and Results In 1388 patients (mean age 50.5 [12.3] years, 34% male) presenting with stable chest pain to Mayo Clinic, Rochester, MN for diagnostic coronary angiography, and who were found to have nonobstructive coronary artery disease (<40% stenosis), we invasively assessed coronary artery endothelial-dependent microvascular and epicardial function by evaluating changes in coronary blood flow (% Δ CBF Ach) and diameter (% Δ CAD Ach), respectively, in response to intracoronary infusions of acetylcholine. Patients were divided into 2 groups: hypothyroidism, defined as a documented history of hypothyroidism or a thyroid-stimulating hormone (TSH) >10.0 mU/mL, n=188, and euthyroidism, defined as an absence of a history of hypothyroidism in the clinical record and/or 0.3<TSH≤10.0 mU/mL, n=1200. Subjects with a history of hypothyroidism had a significantly lower % Δ CBF Ach (48.26 [80.66] versus 64.58 [128.30]) compared to patients with euthyroidism, while the % Δ CAD Ach did not vary significantly between groups. After adjusting for covariates, females with hypothyroidism still had a significantly lower % Δ CBF Ach (estimated difference in % Δ CBF Ach [SE]: −16.79 [8.18]). Conclusions Hypothyroidism in women is associated with microvascular endothelial dysfunction, even after adjusting for confounders, and may explain some of the increased risk of cardiovascular disease in these patients.

What is the association of hypothyroidism with risks of cardiovascular events and mortality? A meta-analysis of 55 cohort studies involving 1,898,314 participants

BackgroundWhether hypothyroidism is an independent risk factor for cardiovascular events is still disputed. We aimed to assess the association between hypothyroidism and risks of cardiovascular events and mortality.MethodsWe searched PubMed and Embase from inception to 29 February 2016. Cohort studies were included with no restriction of hypothyroid states. Priori main outcomes were ischemic heart disease (IHD), cardiac mortality, cardiovascular mortality, and all-cause mortality.ResultsFifty-five cohort studies involving 1,898,314 participants were identified. Patients with hypothyroidism, compared with euthyroidism, experienced higher risks of IHD (relative risk (RR): 1.13; 95% confidence interval (CI): 1.01–1.26), myocardial infarction (MI) (RR: 1.15; 95% CI: 1.05–1.25), cardiac mortality (RR: 1.96; 95% CI: 1.38–2.80), and all-cause mortality (RR: 1.25; 95% CI: 1.13–1.39); subclinical hypothyroidism (SCH; especially with thyrotropin level ≥10 mIU/L) was also associated with higher risks of IHD and cardiac mortality. Moreover, cardiac patients with hypothyroidism, compared with those with euthyroidism, experienced higher risks of cardiac mortality (RR: 2.22; 95% CI: 1.28–3.83) and all-cause mortality (RR: 1.51; 95% CI: 1.26–1.81).ConclusionsHypothyroidism is a risk factor for IHD and cardiac mortality. Hypothyroidism is associated with higher risks of cardiac mortality and all-cause mortality compared with euthyroidism in the general public or in patients with cardiac disease.

Coronary endothelial function testing provides superior discrimination compared with standard clinical risk scoring in prediction of cardiovascular events.

BackgroundEndothelial dysfunction is regarded as the early stage of atherosclerosis and is associated with cardiovascular (CV) events. This study was designed to determine whether assessment of coronary endothelial function (CEF) is safe and can reclassify risk in patients with early coronary artery disease beyond the Framingham risk score (FRS). Methods and resultsCEF was evaluated using intracoronary acetylcholine in 470 patients who presented with chest pain and nonobstructive coronary artery disease. CV events were assessed after a median follow-up of 9.7 years. The association between CEF and CV events was examined, and the net reclassification improvement index (NRI) was used to compare the incremental contribution of CEF when added to FRS.The mean age was 53 years, and 68% of the patients were women with a median FRS of 8. Complications (coronary dissection) occurred in three (0.6%) and CV events in 61 (13%) patients. In univariate analysis, microvascular CEF [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.72–0.97, P=0.032] and epicardial CEF (HR 0.73, 95% CI 0.59–0.90, P=0.01) were found to be significant predictors of CV events, whereas FRS was not (HR 1.05, 95% CI 0.85–1.26, P=0.61). When added to FRS, microvascular CEF correctly reclassified 11.3% of patients [NRI 0.11 (95% CI 0.019–0.21)], epicardial CEF correctly reclassified 12.1% of patients [NRI 0.12 (95% CI −0.02 to 0.26)], and the combined microvascular and epicardial CEF correctly reclassified 22.8% of patients [NRI 0.23 (95% CI 0.08–0.37)]. ConclusionCEF testing is safe and adds value to the FRS, with superior discrimination and risk stratification compared with FRS alone in patients presenting with chest pain or suspected ischemia.

Sudden Cardiac Death From the Perspective of Coronary Artery Disease

Sudden cardiac death accounts for approximately 50% of all deaths attributed to cardiovascular disease in the United States. It is most commonly associated with coronary artery disease and can be its initial manifestation or may occur in the period after an acute myocardial infarction. Decreasing the rate of sudden cardiac death requires the identification and treatment of at-risk patients through evidence-based pharmacotherapy and interventional strategies aimed at primary and secondary prevention. For this review, we searched PubMed for potentially relevant articles published from January 1, 1970, through March 1, 2014, using the following key search terms: sudden cardiac death, ischemic heart disease, coronary artery disease, myocardial infarction, and cardiac arrest. Searches were enhanced by scanning bibliographies of identified articles, and those deemed relevant were selected for full-text review. This review outlines various mechanisms for sudden cardiac death in the setting of coronary artery disease, describes risk factors for sudden cardiac death, explores the management of cardiac arrest, and outlines optimal practice for the monitoring and treatment of patients after an acute ST-segment elevation myocardial infarction to decrease the risk of sudden death.

Left Internal Mammary Artery Versus Coronary Stents: Impact on Downstream Coronary Stenoses and Conduit Patency

Background The study compared downstream coronary and conduit disease progression in the left anterior descending coronary artery treated with coronary artery bypass grafting using the left internal mammary artery (LIMA) versus percutaneous coronary intervention with bare metal stent (BMS) or drug eluting stent (DES). Methods and Results A total of 12 301 consecutive patients underwent isolated primary coronary revascularization, of which 2386 met our inclusion criteria (Percutaneous coronary intervention, n=1450; coronary artery bypass grafting, n=936). Propensity score analysis matched 628 patients, of which 468 were treated to the left anterior descending with coronary artery bypass grafting with LIMA (n=314), percutaneous coronary intervention with BMS (n=94), and DES (n=60). Coronary angiograms were analyzed by quantitative coronary angiography (QCA; n=433). Cumulative downstream coronary and conduit disease progression were estimated by Kaplan–Meier method and effect of treatment type by Cox proportional hazard models. Patients treated with LIMA had significantly lower risk of downstream coronary disease progression at follow‐up angiogram compared with BMS and DES (hazard ratio [HR] [95% CI], 0.34; [0.20–0.59]; P=0.0002; and HR [95% CI], 0.39; [0.20–0.79]; P=0.01, respectively). LIMA was associated with a lower risk of conduit disease progression compared to BMS and DES (HR [95% CI], 0.18; [0.12–0.28]; P<0.001; and HR [95% CI], 0.27; [0.16–0.46]; P<0.001, respectively). BMS was associated with higher HR for downstream coronary and conduit disease progression compared with DES, but the difference did not reach statistical significance (HR [95% CI], 1.13; [0.57–2.36]; P=0.73; and HR [95% CI], 1.46; [0.88–2.50]; P=0.14, respectively). Conclusions LIMA grafting to left anterior descending is associated with significantly lower risk of downstream coronary and conduit disease progression compared to percutaneous coronary intervention with BMS and DES.

Voice Signal Characteristics Are Independently Associated With Coronary Artery Disease

Objective: Voice signal analysis is an emerging noninvasive diagnostic tool. The current study tested the hypothesis that patient voice signal characteristics are associated with the presence of coronary artery disease (CAD). Methods: The study population included 138 patients who were enrolled between January 1, 2015, and February 28, 2017: 37 control subjects and 101 subjects who underwent planned coronary angiogram. All subjects had their voice signal recorded to their smartphone 3 times: reading a text, describing a positive emotional experience, and describing a negative emotional experience. The Mel Frequency Cepstral Coefficients were used to extract prespecified voice features from all 3 recordings. Voice was recorded before the angiogram and analysis was blinded with respect to patient data. Results: Final study cohort included 101 patients, of whom 71 (71%) had CAD. Compared with subjects without CAD, patients with CAD were older (median, 63 years; interquartile range [IQR], 55‐68 years vs median, 53 years; IQR, 42‐66 years; P=.003) and had a higher 10‐year atherosclerotic cardiovascular disease (ASCVD) risk score (9.4%; IQR, 5.0‐18.7 vs 2.7%; IQR, 1.6‐11.8; P=.005). Univariate binary logistic regression analysis identified 5 voice features that were associated with CAD (P<.05 for all). Multivariate binary logistic regression with adjustment for ASCVD risk score identified 2 voice features that were independently associated with CAD (odds ratio [OR], 0.37; 95% CI, 0.18‐0.79; and 4.01; 95% CI, 1.25‐12.84; P=.009 and P=.02, respectively). Both features were more strongly associated with CAD when patients were asked to describe an emotionally significant experience. Conclusion: This study suggests a potential relationship between voice characteristics and CAD, with clinical implications for telemedicine—when clinical health care is provided at a distance.

Association Between Work‐Related Stress and Coronary Heart Disease: A Review of Prospective Studies Through the Job Strain, Effort‐Reward Balance, and Organizational Justice Models

Work‐related stress is an example of a psychosocial risk factor that has become of interest in todays ever‐demanding, fast‐paced, and globalized society, although its link to adverse health and in particular coronary heart disease (CHD) is incompletely understood. In this review, we will

Reply: Microvascular Function in Ischemic Heart Disease: There May Be Room for Improvement

We recently showed that coronary microvascular dysfunction (CMD) is present in up to two-thirds of patients presenting with signs and symptoms of stable myocardial ischemia and nonobstructive coronary artery disease at coronary angiography [(1)][1]. Although it is known that CMD is associated with