Sara, Jaskanwal Deep Singh

Aims Cardiovascular health metrics predict the risk not only of cardiovascular diseases but also of several types of cancers. Microvascular endothelial dysfunction can predict future cardiovascular adverse events, but the predictive value of microvascular endothelial dysfunction for future risk of solid-tumor cancer has not been characterized. Methods A total of 488 patients who underwent microvascular endothelial function assessment using reactive hyperemia peripheral arterial tonometry were included in this study. Microvascular endothelial dysfunction was defined as a reactive hyperemia peripheral arterial tonometry index ≤2.0. Results Of 221 patients with a baseline reactive hyperemia peripheral arterial tonometry index ≤2.0, 21 patients (9.5%) were diagnosed with incident solid-tumor cancer during follow-up, whereas of 267 patients with a baseline reactive hyperemia peripheral arterial tonometry index >2.0, 10 patients (3.7%) were diagnosed with incident solid-tumor cancer during follow-up ( p = 0.009). Patients with a reactive hyperemia peripheral arterial tonometry index ≤2.0 had lower solid-tumor cancer-free survival compared to patients with a reactive hyperemia peripheral arterial tonometry index >2.0 (log-rank p = 0.017) (median follow-up 6.0 (3.0–9.1) years). Cox proportional hazard analyses showed that a reactive hyperemia peripheral arterial tonometry index ≤2.0 predicted the incidence of solid-tumor cancer, with a hazard ratio of 2.52 (95% confidence interval 1.17–5.45; p = 0.019) after adjusting for age, sex, and coronary artery disease, 2.83 (95% confidence interval 1.30–6.17; p = 0.009) after adjusting for diabetes mellitus, hypertension, smoking status, and body mass index >30 kg/m2, 2.79 (95% confidence interval 1.21–6.41; p = 0.016) after adjusting for fasting plasma glucose, systolic blood pressure, smoking status (current or former), and body mass index, and 2.43 (95% confidence interval 1.10–5.34; p = 0.028) after adjusting for Framingham risk score. Conclusion Microvascular endothelial dysfunction, as defined by a reactive hyperemia peripheral arterial tonometry index ≤2.0, was associated with a greater than two-fold increased risk of solid-tumor cancer. Microvascular endothelial dysfunction may be a useful marker to predict the future risk of solid-tumor cancer, in addition to its known ability to predict cardiovascular disease. Further research is necessary to develop adequate cancer screening strategies for patients with microvascular endothelial dysfunction.

Background: We aimed to test the hypothesis that peripheral endothelial dysfunction induced by mental stress may predict cardiovascular events after acute coronary syndrome beyond traditional cardiovascular disease risk factors. Methods: This was a prospective study in which 417 patients who had acute coronary syndrome were enrolled in two sites at the US and Qatar. Cardiovascular disease risk factors such as past medical history, blood pressure, heart rate, peripheral endothelial dysfunction, and response to three different mental stress examinations (Stroop Color Word, Arithmetic, and Spiral Omnibus) as assessed by ratio of reactive hyperemia tonometry (EndoPAT) with stress over EndoPAT at rest were obtained at baseline. Major adverse cardiac events were then recorded at 1 year after the index event. Results: There were no differences in baseline peripheral endothelial dysfunction or vascular response to mental stress between the US vs. Qatar patients. Women were more likely to experience major adverse cardiac events in the year following acute coronary syndrome (relative risk 2.42, 95% confidence interval 1.53–3.84, P = 0.044), and had a significantly lower mental stress ratio compared to women who did not (1.0 ± 0.17 vs. 1.20 ± 0.17, P = 0.04). In multivariate analyses stratified by sex, baseline peripheral endothelial dysfunction (EndoPAT < 1.7) (χ2 = 8.0, P = 0.005) and mental stress ratio (χ2 = 7.7, P = 0.006), were independently predictive of major adverse cardiac events in women, but not men. Conclusion: The current study demonstrates that in women both baseline endothelial function and vascular function in response to mental stress ratio are predictive of worse cardiovascular disease outcomes 1 year after acute coronary syndrome. The study may suggest an important mechanism for adverse clinical outcomes in women following acute coronary syndrome.

Abstract Background Patients with type 2 diabetes are at an increased risk of cardiovascular events compared to individuals without diabetes. The role glycemic control plays in reducing cardiovascular risk remains uncertain. Coronary microvascular dysfunction (CMD) is more frequent in women compared to men, is prevalent in patients with type 2 diabetes and is linked to adverse cardiovascular events. We compared the association between CMD and glycemic control across sexes in patients with chest pain and non-obstructive coronary artery disease (CAD). Methods Patients with chest pain who were found to have non-obstructive CAD (stenosis <40%) at angiography underwent an invasive assessment of endothelial-independent and endothelial–dependent coronary microvascular function. Using a Doppler guidewire, endothelial-independent microvascular function was assessed by measuring the coronary flow velocity in response to intracoronary adenosine and comparing this to baseline to calculate the coronary flow reserve ratio (CFRAdn). A CFRAdn ≤2.5 was considered abnormal. Endothelial-dependent microvascular function was assessed by measuring the percent change in coronary blood flow in response to intracoronary infusions of acetylcholine (%ΔCBFAch), with a %ΔCBFAch ≤50% considered abnormal. Patients were classified as having normal versus abnormal CFRAdn and %ΔCBFAch. Measurements of HbA1c and fasting serum glucose were obtained at the time of catheterization and compared between groups after stratification by sex. Results Between 1993 and 2012, 1,469 patients (mean age 50.4 years, 35% male) underwent coronary angiography and invasive testing for CMD, of which 129 (8.8%) had type 2 diabetes. Fifty one (39.5%) had an abnormal %ΔCBFAch and 49 (38.0%) had an abnormal CFRAdn. Conventional cardiovascular risk factors did not vary significantly between groups. Females with an abnormal CFRAdn or abnormal %ΔCBFAch had a significantly higher HbA1c compared to those with a normal CFRAdn or %ΔCBFAch respectively: HbA1c % (standard deviation) 7.4 (2.1) vs. 6.5 (1.1), p=0.035 and 7.3 (1.9) vs. 6.4 (1.2), p=0.022, respectively. Females with an abnormal CFRAdn had significantly higher fasting serum glucose concentrations compared to those with a normal CFRAdn: fasting serum glucose mg/dL (standard deviation) 144.4 (55.6) vs. 121.9 (28.1), p=0.035. These effects were not observed in men. Amongst female diabetics, a higher HbA1c was significantly associated with any CMD after adjusting for covariates: odds ratio (95% confidence interval) 1.69 (1.01 – 2.86) p=0.049; and a fasting serum glucose >140 mg/dL was significantly associated with an abnormal CFRAdn, 4.28 (1.43–12.81). Conclusion Poor glycemic control is associated with CMD in females with diabete who present with chest pain and non-obstructive CAD. These findings highlight the importance of sex-specific risk stratification models and treatment strategies when managing cardiovascular risk in diabetics. Acknowledgement/Funding Mayo Foundation

Background Women with non‐obstructive coronary artery disease have increased cardiovascular morbidity. The role of risk factors in this population has yet to be established. We aimed to study the predictive effect of triglycerides and the triglyceride/high‐density lipoprotein ratio on major adverse cardiovascular events (MACE) in patients with non‐obstructive coronary artery disease, and to explore the role of lipid lowering therapy in modifying this risk. Methods and Results This is a prospective cohort study enrolling patients with anginal symptoms referred to the cardiac catheterization laboratory for suspected ischemia, who were subsequently diagnosed with non‐obstructive coronary artery disease, defined as no stenosis >20% on angiography. All patients had baseline laboratory testing and were followed for 7.8±4.3 years for the development of major adverse cardiovascular events. We performed Cox proportional hazard testing to determine the effect of triglycerides on risk of major adverse cardiovascular events among men and women by baseline statin use. A total of 462 patients were included. Median age was 53 (Q1, Q3: 45, 62) years. In a Cox proportional hazard model stratified by statin use adjusting for confounders, among those not on baseline statins, triglycerides were independently predictive of major adverse cardiovascular events in women (per 50 mg/dL risk ratio: hazard ratio 1.25 [95% CI : 1.06, 1.47]; P =0.01). This was not true among men. The interaction between triglycerides and sex, and triglycerides and statin was statistically significant. Conclusions Triglyceride levels may play a key role in predicting cardiovascular‐specific risk in women, and statin use may be protective. Further investigation is necessary to better delineate the role of statin use in preventing cardiovascular risk.

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.

Diagnosing patients simply with heart failure or nephrotic syndrome is insufficient, and clinicians should always search for the underlying causes of these syndromes. Amyloidosis represents a rare group of diseases in which abnormal protein, namely amyloid fibrils, build up in various organs. Presentation depends on which organ systems are involved, and symptoms could include breathlessness associated with fluid overload suggestive of cardiac and/or renal involvement and diarrhoea and weight loss, suggestive of gastrointestinal involvement. The authors present a case of congestive cardiac failure and nephrotic range proteinuria in a patient with persistent fluid overload secondary toamyloid light-chain (AL) amyloidosis.

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 .

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-P IMA ) were assessed with validated assays. Cholesterol efflux capacity and HDL-P IMA 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-P IMA remained significant predictors of ED status. HDL-P IMA 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-P IMA are reduced in subjects with coronary ED, independently of HDL-C. Alterations in HDL-P IMA 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.