Relation of microvascular dysfunction to exercise capacity and symptoms in patients with severe aortic stenosis

Objective: The aim of this study was to assess the impact of left ventricular hypertrophy, myocardial fibrosis, myocardial perfusion reserve (MPR) and diastolic dysfunction on objectively measured aerobic exercise capacity (peak VO$_{2}$) in severe aortic stenosis (AS). Background: The management of asymptomatic patients with severe AS remains controversial and clinical practice varies. Echocardiographic measures of severity do not discriminate between symptomatic status or predict exercise capacity. The purpose of this study was to investigate the mechanisms contributing to symptom generation and exercise intolerance. This needs to be fully understood to optimise the management of asymptomatic AS. Methods: Patients were prospectively enrolled from a single cardiac surgical centre. Inclusion criteria: age 18-85, isolated severe AS referred for valve replacement. Exclusion criteria: syncope; other moderate/severe valve disease, previous valve surgery, obstructive coronary artery disease (>50% luminal stenosis on invasive angiography), chronic obstructive pulmonary disease, atrial fibrillation, estimated glomerular filtration rate <30mL/min. Investigations and primary outcome measures; cardiac magnetic resonance (CMR) - left ventricular mass index (LVMI), MPR (calculated from absolute myocardial blood flow during adenosine hyperaemia and rest determined by model-independent deconvolution of signal intensity curves with an arterial input function), late gadolinium enhancement (LGE); echocardiography - AS severity, tissue Doppler-derived diastolic function; symptom-limited bicycle ergometer cardiopulmonary exercise testing (CPEX) - peak VO$_{2}$. Linear regression investigated possible predictors of continuous outcome measures. Stepwise selection methods were used to determine the most important predictors of outcome. Results: Four patients with variable LVMI, LGE and MPR are shown, Figure 1. Univariate analyses and results from the stepwise model selection for peak VO$_{2}$ are summarised in Table 1. Only MPR was of independent significance in predicting age and sex corrected peak VO$_{2}$. The relationship between peak VO$_{2}$ and MPR is shown, Figure 2. Patients with higher NYHA Class had lower MPR (p=0.001). Examining predictors of MPR the best stepwise model contained LVMI and LGE category as independent predictors, Table 2. Conclusions: MPR is a novel independent predictor of peak VO$_{2}$ and is inversely related to NYHA functional class in severe AS. Microvascular dysfunction is determined by a combination of factors including AS severity, LVMI, diastolic perfusion time, myocardial fibrosis and LV filling pressure. Further work is required to determine the clinical significance of microvascular dysfunction in AS

Quantum-over-classical Advantage in Solving Multiplayer Games

We study the applicability of quantum algorithms in computational game theory and generalize some results related to Subtraction games, which are sometimes referred to as one-heap Nim games. In quantum game theory, a subset of Subtraction games became the first explicitly defined class of zero-sum combinatorial games with provable separation between quantum and classical complexity of solving them. For a narrower subset of Subtraction games, an exact quantum sublinear algorithm is known that surpasses all deterministic algorithms for finding solutions with probability $1$. Typically, both Nim and Subtraction games are defined for only two players. We extend some known results to games for three or more players, while maintaining the same classical and quantum complexities: $\Theta\left(n^2\right)$ and $\tilde{O}\left(n^{1.5}\right)$ respectively

19th Annual Conference on Legal Issues For Financial Institutions

Materials from the 19th Annual Conference on Legal Issues For Financial Institutions held by UK/CLE in May 1999

Diabetes and cardiovascular disease: A statement for healthcare professionals from the American Heart Association

This statement examines the cardiovascular complications of diabetes mellitus and considers opportunities for their prevention. These complications include coronary heart disease (CHD), stroke, peripheral arterial disease, nephropathy, retinopathy, and possibly neuropathy and cardiomyopathy. Because of the aging of the population and an increasing prevalence of obesity and sedentary life habits in the United States, the prevalence of diabetes is increasing. Thus, diabetes must take its place alongside the other major risk factors as important causes of cardiovascular disease (CVD). In fact, from the point of view of cardiovascular medicine, it may be appropriate to say, “diabetes is a cardiovascular disease.

Use of global coronary heart disease risk assessment in practice: a cross-sectional survey of a sample of U.S. physicians

<p>Abstract</p> <p>Background</p> <p>Global coronary heart disease (CHD) risk assessment is recommended to guide primary preventive pharmacotherapy. However, little is known about physicians' understanding and use of global CHD risk assessment. Our objective was to examine US physicians' awareness, use, and attitudes regarding global CHD risk assessment in clinical practice, and how these vary by provider specialty.</p> <p>Methods</p> <p>Using a web-based survey of US family physicians, general internists, and cardiologists, we examined awareness of tools available to calculate CHD risk, method and use of CHD risk assessment, attitudes towards CHD risk assessment, and frequency of using CHD risk assessment to guide recommendations of aspirin, lipid-lowering and blood pressure (BP) lowering therapies for primary prevention. Characteristics of physicians indicating they use CHD risk assessments were compared in unadjusted and adjusted analyses.</p> <p>Results</p> <p>A total of 952 physicians completed the questionnaire, with 92% reporting awareness of tools available to calculate CHD global risk. Among those aware of such tools, over 80% agreed that CHD risk calculation is useful, improves patient care, and leads to better decisions about recommending preventive therapies. However, only 41% use CHD risk assessment in practice. The most commonly reported barrier to CHD risk assessment is that it is too time consuming. Among respondents who calculate global CHD risk, 69% indicated they use it to guide lipid lowering therapy recommendations; 54% use it to guide aspirin therapy recommendations; and 48% use it to guide BP lowering therapy. Only 40% of respondents who use global CHD risk routinely tell patients their risk. Use of a personal digital assistant or smart phone was associated with reported use of CHD risk assessment (adjusted OR 1.58; 95% CI 1.17-2.12).</p> <p>Conclusions</p> <p>Reported awareness of tools to calculate global CHD risk appears high, but the majority of physicians in this sample do not use CHD risk assessments in practice. A minority of physicians in this sample use global CHD risk to guide prescription decisions or to motivate patients. Educational interventions and system improvements to improve physicians' effective use of global CHD risk assessment should be developed and tested.</p

New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.

Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes

Global Burden of Cardiovascular Diseases and Risk Factors, 1990-2019 : Update From the GBD 2019 Study

Cardiovascular diseases (CVDs), principally ischemic heart disease (IHD) and stroke, are the leading cause of global mortality and a major contributor to disability. This paper reviews the magnitude of total CVD burden, including 13 underlying causes of cardiovascular death and 9 related risk factors, using estimates from the Global Burden of Disease (GBD) Study 2019. GBD, an ongoing multinational collaboration to provide comparable and consistent estimates of population health over time, used all available population-level data sources on incidence, prevalence, case fatality, mortality, and health risks to produce estimates for 204 countries and territories from 1990 to 2019. Prevalent cases of total CVD nearly doubled from 271 million (95% uncertainty interval [UI]: 257 to 285 million) in 1990 to 523 million (95% UI: 497 to 550 million) in 2019, and the number of CVD deaths steadily increased from 12.1 million (95% UI:11.4 to 12.6 million) in 1990, reaching 18.6 million (95% UI: 17.1 to 19.7 million) in 2019. The global trends for disability-adjusted life years (DALYs) and years of life lost also increased significantly, and years lived with disability doubled from 17.7 million (95% UI: 12.9 to 22.5 million) to 34.4 million (95% UI:24.9 to 43.6 million) over that period. The total number of DALYs due to IHD has risen steadily since 1990, reaching 182 million (95% UI: 170 to 194 million) DALYs, 9.14 million (95% UI: 8.40 to 9.74 million) deaths in the year 2019, and 197 million (95% UI: 178 to 220 million) prevalent cases of IHD in 2019. The total number of DALYs due to stroke has risen steadily since 1990, reaching 143 million (95% UI: 133 to 153 million) DALYs, 6.55 million (95% UI: 6.00 to 7.02 million) deaths in the year 2019, and 101 million (95% UI: 93.2 to 111 million) prevalent cases of stroke in 2019. Cardiovascular diseases remain the leading cause of disease burden in the world. CVD burden continues its decades-long rise for almost all countries outside high-income countries, and alarmingly, the age-standardized rate of CVD has begun to rise in some locations where it was previously declining in high-income countries. There is an urgent need to focus on implementing existing cost-effective policies and interventions if the world is to meet the targets for Sustainable Development Goal 3 and achieve a 30% reduction in premature mortality due to noncommunicable diseases

Global Burden of Cardiovascular Diseases and Risk Factors, 1990–2019: Update From the GBD 2019 Study

Cardiovascular diseases (CVDs), principally ischemic heart disease (IHD) and stroke, are the leading cause of global mortality and a major contributor to disability. This paper reviews the magnitude of total CVD burden, including 13 underlying causes of cardiovascular death and 9 related risk factors, using estimates from the Global Burden of Disease (GBD) Study 2019. GBD, an ongoing multinational collaboration to provide comparable and consistent estimates of population health over time, used all available population-level data sources on incidence, prevalence, case fatality, mortality, and health risks to produce estimates for 204 countries and territories from 1990 to 2019. Prevalent cases of total CVD nearly doubled from 271 million (95% uncertainty interval [UI]: 257 to 285 million) in 1990 to 523 million (95% UI: 497 to 550 million) in 2019, and the number of CVD deaths steadily increased from 12.1 million (95% UI:11.4 to 12.6 million) in 1990, reaching 18.6 million (95% UI: 17.1 to 19.7 million) in 2019. The global trends for disability-adjusted life years (DALYs) and years of life lost also increased significantly, and years lived with disability doubled from 17.7 million (95% UI: 12.9 to 22.5 million) to 34.4 million (95% UI:24.9 to 43.6 million) over that period. The total number of DALYs due to IHD has risen steadily since 1990, reaching 182 million (95% UI: 170 to 194 million) DALYs, 9.14 million (95% UI: 8.40 to 9.74 million) deaths in the year 2019, and 197 million (95% UI: 178 to 220 million) prevalent cases of IHD in 2019. The total number of DALYs due to stroke has risen steadily since 1990, reaching 143 million (95% UI: 133 to 153 million) DALYs, 6.55 million (95% UI: 6.00 to 7.02 million) deaths in the year 2019, and 101 million (95% UI: 93.2 to 111 million) prevalent cases of stroke in 2019. Cardiovascular diseases remain the leading cause of disease burden in the world. CVD burden continues its decades-long rise for almost all countries outside high-income countries, and alarmingly, the age-standardized rate of CVD has begun to rise in some locations where it was previously declining in high-income countries. There is an urgent need to focus on implementing existing cost-effective policies and interventions if the world is to meet the targets for Sustainable Development Goal 3 and achieve a 30% reduction in premature mortality due to noncommunicable diseases