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Heartbeat: Challenges in primary prevention of cardiovascular disease

2017-03-13T07:00:47-07:00

In addition to encouraging a healthy lifestyle and treating modifiable risk factors, one of the mainstays for primary prevention of cardiovascular disease (CVD) is the use of statin therapy in people with increased CVD risk. However, it is confusing for clinicians and patients that guidelines from different organisations make different recommendations about who to treat and how to set treatment goals.1 In my editorial in this issue of Heart, the 3 major differences between guidelines are summarised: (1) how CVD risk is calculated, (2) the risk threshold for recommending statin therapy and (3) the use of treatment with a fixed statin dose versus therapy adjusted to achieve a serum low density lipoprotein (LDL) target. The rationale for different risk scores in each guideline is because CVD risk prediction varies in different populations; ideally the risk score was derived from the population being treated. Evidence suggests that statin...




Statins for primary prevention of cardiovascular disease: Patients need better tools to navigate divergent recommendations

2017-03-13T07:00:47-07:00

Statins are beneficial in patients with known cardiovascular disease (CVD) but less well established for primary prevention in asymptomatic patients.1 At least five authoritative guidelines, including the recent publication from the US Preventive Services Task Force, cover this issue.2–7 Their differing recommendations, however, suggest considerable uncertainty in the underlying data, causing confusion for both clinicians and patients.

The guidelines share several common themes. The essential elements for primary prevention include a healthy lifestyle, treatment of modifiable risk factors, and measurement of serum lipid concentrations in patients aged over 40 years. They agree that statins are appropriate in patients with a high risk of cardiovascular disease—for example, people over 40 with diabetes. All guidelines also recommend statins in other patients with increased cardiovascular risk but with considerable divergence in the details.

The US task force guideline...




Gender disparities in cardiovascular disease prevention

2017-03-13T07:00:47-07:00

Cardiovascular disease (CVD) has historically been viewed as a man’s disease, yet more women than men die from CVD every year.1 Even with national campaigns aimed at increasing awareness of CVD in women, the number of women diagnosed with and dying from CVD continues to increase across the world.1 While biological differences between women and men likely contribute to these differences in outcomes, disparities in cardiovascular care may also play a role. Potential areas in cardiovascular prevention where disparities may occur include inadequate screening, untimely diagnosis and/or lack of appropriate treatment of CVD in women compared with men.

In their Heart paper, Hyun and colleagues evaluated potential gender disparities in cardiovascular risk screening and preventive medication use among patients with high cardiovascular risk enrolled in the Treatment of cardiovascular Risk in Primary care using Electronic Decision suppOrt (TORPEDO) study.2 3 This cluster-randomised trial conducted...




Beyond left ventricular mass: the prognostic power of left ventricular shape

2017-03-13T07:00:47-07:00

Introduction

In recent years, our knowledge about the mechanisms leading to acute and chronic changes in cardiac morphology and function has been progressively expanding.

Nowadays, human studies on cardiac remodelling mostly rely on a variety of non-invasive, rapidly evolving imaging techniques. Standard echocardiography is an established, cost-effective, available cardiac imaging technique currently applied to detect and quantify the severity of morphological and functional alterations of the heart. The pivotal role of echocardiography has been further powered by new ultrasonographic instruments, primarily two-dimensional and three-dimensional speckle tracking imaging devices which provide a comprehensive assessment of myocardial mechanics.

Nuclear and MRI techniques are reliable, highly reproducible methods increasingly applied in clinical and research settings. In particular, cardiac MRI has the undisputed potential to generate high-quality images of the heart at much higher resolution than echocardiographic and nuclear techniques.

Since the early 1990s, prospective epidemiological studies have consistently shown that echocardiographic...




Cost-effectiveness of the polypill versus risk assessment for prevention of cardiovascular disease

2017-03-13T07:00:47-07:00

Objective

There is an international trend towards recommending medication to prevent cardiovascular disease (CVD) in individuals at increasingly lower cardiovascular risk. We assessed the cost-effectiveness of a population approach with a polypill including a statin (simvastatin 20 mg) and three antihypertensive agents (amlodipine 2.5 mg, losartan 25 mg and hydrochlorothiazide 12.5 mg) and periodic risk assessment with different risk thresholds.

Methods

We developed a microsimulation model for lifetime predictions of CVD events, diabetes, and death in 259 146 asymptomatic UK Biobank participants aged 40–69 years. We assessed incremental costs and quality-adjusted life-years (QALYs) for polypill scenarios with the same combination of agents and doses but differing for starting age, and periodic risk assessment with 10-year CVD risk thresholds of 10% and 20%.

Results

Restrictive risk assessment, in which statins and antihypertensives were prescribed when risk exceeded 20%, was the optimal strategy gaining 123 QALYs (95% credible interval (CI) –173 to 387) per 10 000 individuals at an extra cost of £1.45 million (95% CI 0.89 to 1.94) as compared with current practice. Although less restrictive risk assessment and polypill scenarios prevented more CVD events and attained larger survival gains, these benefits were offset by the additional costs and disutility of daily medication use. Lowering the risk threshold for prescription of statins to 10% was economically unattractive, costing £40 000 per QALY gained. Starting the polypill from age 60 onwards became the most cost-effective scenario when annual drug prices were reduced below £240. All polypill scenarios would save costs at prices below £50.

Conclusions

Periodic risk assessment using lower risk thresholds is unlikely to be cost-effective. The polypill would become cost-effective if drug prices were reduced.




Gender inequalities in cardiovascular risk factor assessment and management in primary healthcare

2017-03-13T07:00:47-07:00

Objectives

To quantify contemporary differences in cardiovascular disease (CVD) risk factor assessment and management between women and men in Australian primary healthcare services.

Methods

Records of routinely attending patients were sampled from 60 Australian primary healthcare services in 2012 for the Treatment of Cardiovascular Risk using Electronic Decision Support study. Multivariable logistic regression models were used to compare the rate of CVD risk factor assessment and recommended medication prescriptions, by gender.

Results

Of 53 085 patients, 58% were female. Adjusting for demographic and clinical characteristics, women were less likely to have sufficient risk factors measured for CVD risk assessment (OR (95% CI): 0.88 (0.81 to 0.96)). Among 13 294 patients (47% women) in the CVD/high CVD risk subgroup, the adjusted odds of prescription of guideline-recommended medications were greater for women than men: 1.12 (1.01 to 1.23). However, there was heterogeneity by age (p <0.001), women in the CVD/high CVD risk subgroup aged 35–54 years were less likely to be prescribed the medications (0.63 (0.52 to 0.77)), and women in the CVD/high CVD risk subgroup aged ≥65 years were more likely to be prescribed the medications (1.34 (1.17 to 1.54)) than their male counterparts.

Conclusions

Women attending primary healthcare services in Australia were less likely than men to have risk factors measured and recorded such that absolute CVD risk can be assessed. For those with, or at high risk of, CVD, the prescription of appropriate preventive medications was more frequent in older women, but less frequent in younger women, compared with their male counterparts.

Trial registration number

12611000478910, Pre-results.




Left ventricular shape predicts different types of cardiovascular events in the general population

2017-03-13T07:00:47-07:00

Objective

To investigate whether sphericity volume index (SVI), an indicator of left ventricular (LV) remodelling, predicts incident cardiovascular events (coronary heart disease, CHD; all cardiovascular disease, CVD; heart failure, HF; atrial fibrillation, AF) over 10 years of follow-up in a multiethnic population (Multi-Ethnic Study of Atherosclerosis).

Methods

5004 participants free of known CVD had magnetic resonance imaging (MRI) in 2000–2002. Cine images were analysed to compute, equivalent to LV volume/volume of sphere with length of LV as the diameter. The highest (greatest sphericity) and lowest (lowest sphericity) quintiles of SVI were compared against the reference group (2–4 quintiles combined). Risk-factor adjusted hazard's ratio (HR) from Cox regression assessed the predictive performance of SVI at end-diastole (ED) and end-systole (ES) to predict incident outcomes over 10 years in retrospective interpretation of prospective data.

Results

At baseline, participants were aged 61±10 years; 52% men and 39%/13%/26%/22% Cauc/Chinese/Afr-Amer/Hispanic. Low sphericity was associated with higher Framingham CVD risk, greater coronary calcium score and higher N-terminal pro-brain natriuretic peptide (NT-proBNP); while increased sphericity was associated with higher NT-proBNP and lower ejection fraction. Low sphericity predicted incident CHD (HR: 1.48, 1.55–2.59 at ED) and CVD (HR: 1.82, 1.47–2.27 at ED). However, both low (HR: 1.81, 1.20–2.73 at ES) and high (HR: 2.21, 1.41–3.46 at ES) sphericity predicted incident HF. High sphericity also predicted AF.

Conclusions

In a multiethnic population free of CVD at baseline, lowest sphericity was a predictor of incident CHD, CVD and HF over a 10-year follow-up period. Extreme sphericity was a strong predictor of incident HF and AF. SVI improved risk prediction models beyond established risk factors only for HF, but not for all CVD or CHD.




A case of recent myocardial infarction with cardiac failure

2017-03-13T07:00:47-07:00

Clinical introduction

A 50-year-old hypertensive smoker presented with a typical angina of 2 days duration. An urgent ECG revealed extensive anterior wall myocardial infarction. In view of the delayed presentation, the patient was conservatively managed with heparin. In-hospital echocardiogram showed akinesia of entire left anterior descending artery (LAD) territory with severe left ventricular (LV) dysfunction. He was discharged with a plan for early coronary intervention. However, he presented a fortnight later with acute pulmonary oedema. General appraisal revealed a restless individual who was dyspnoeic and diaphoretic at rest. On clinical examination, the patient was in hypotension with features of biventricular failure. A 12-lead ECG showed QS pattern with persistent ST segment elevation in precordial leads. The chest radiograph demonstrated features of pulmonary oedema, cardiomegaly and bilateral pleural effusion. Creatine Phosphokinase-MB (CPK-MB) was negative. A preliminary transthoracic echocardiography was done (figure 1 and see online ).

Question

What is the most likely diagnosis based on the echocardiogram?

  • LV pseudo-aneurysm with contained rupture

  • Dissecting intramural haematoma of LV apex

  • Ventricular apical aneurysm with thrombus

  • LV non-compaction with prominent ventricular trabaculations




  • Intracoronary nitrite suppresses the inflammatory response following primary percutaneous coronary intervention

    2017-03-13T07:00:47-07:00

    Objective

    Recent work suggests that intracoronary nitrite reduces myocardial infarct size following primary percutaneous coronary intervention (PPCI) for acute myocardial infarction (AMI), although the exact mechanisms are unclear. We explored the effects of nitrite on reperfusion-induced inflammation, by assessing the levels of specific pro-inflammatory mediators, chemokines and adhesion molecules in plasma and circulating cell subtypes as exploratory end points in the NITRITE-AMI cohort.

    Methods

    Peripheral blood leucocyte subsets, cell adhesion molecules, high-sensitivity C reactive protein (hs-CRP), the monocyte and neutrophil chemoattractants CCL2 and CXCL1, CXCL5, respectively were measured in the blood of patients who received either intracoronary sodium nitrite (N=40) or placebo (N=40) during PPCI for AMI. Major adverse cardiac events were recorded at 3 years post-PPCI.

    Results

    In the placebo-treated patients, total circulating neutrophil numbers and levels of hs-CRP were raised postreperfusion and then decreased over time; in nitrite-treated patients these changes were suppressed compared with placebo up to 6 months post-PPCI (p<0.01). This effect was associated with reduced expression of neutrophil CD11b, plasma CXCL1, CXCL5 and CCL2 levels (p<0.05). There were no differences in the number of other any other leucocyte population measured (monocytes and lymphocytes) or activation markers expressed by these cells between the treatment groups. These effects were associated with a reduction in both microvascular obstruction and infarct size.

    Conclusions

    Important reductions in neutrophil numbers and activation post-PPCI in patients with ST elevated myocardial infarction were associated with nitrite treatment, an effect we propose likely underlies, at least in part, the beneficial effects of nitrite upon infarct size.

    Trial registration number

    NCT01584453.




    The clinical efficacy and long-term prognostic value of stress echocardiography in octogenarians

    2017-03-13T07:00:47-07:00

    Introduction

    Although stress echocardiography (SE) is invaluable in younger populations, its prognostic value may be attenuated in the elderly due to shorter life expectancy and the frequent presence of severe comorbidities. This study sought to evaluate the clinical effectiveness of SE in octogenarians, particularly its prognostic value over clinical variables, in predicting hard events.

    Methods

    A total of 374 consecutive octogenarians who underwent SE for evaluation of coronary artery disease (CAD) were assessed for feasibility, diagnostic accuracy and safety of the test, and followed up for hard outcomes (all-cause mortality, cardiovascular (CV) deaths and non-fatal myocardial infarction (NFMI)). Cox regression analysis was performed to identify predictors of outcome.

    Results

    Of the 374 tests, 360 (96.3%) were diagnostic. Of the 50 patients with inducible ischaemia, 33 patients (66%) proceeded to angiography of which 27 (82%) patients had significant CAD. During long-term follow-up of 4.0±2.0 years, there were 127 deaths and 36 NFMIs. The annualised mortality, NFMI and combined mortality /NFMI rates were 8.1%, 1.8% and 9.4% for patients with a normal SE and 12.1%, 5.5% and 14.1% for those with an abnormal SE, respectively. Predictors of NFMI on multivariate analysis were prior CAD (HR 2.89, CI 1.03 to 8.15, p=0.045), peripheral vascular disease (HR 3.33, CI 1.18 to 9.45, p=0.02), and inducible ischaemia (HR 3.97, CI 1.49 to 10.55, p=0.006). In patients without prior history of CAD, inducible ischaemia was the only independent predictor of NFMI (HR 8.72, CI 1.46 to 52.2, p=0.018). The larger the extent of ischaemia, the greater the incidence of NFMI. The independent predictors of CV events (NFMI or CV mortality) were PAD (HR 2.81, CI 1.21 to 6.52, p=0.016) and peak wall motion score index (HR 5.71, CI 1.67 to 19.6, p=0.006). Although inducible ischaemia predicted all-cause mortality on unadjusted analysis, it did not on multivariate analysis.

    Conclusions

    In octogenarians, SE demonstrated excellent feasibility, safety and diagnostic accuracy. SE parameters were independent predictors of NFMI and CV events, and the presence of inducible ischaemia was associated with a 50% increase in all-cause mortality.




    Associations between cardiorespiratory fitness and the metabolic syndrome in British men

    2017-03-13T07:00:47-07:00

    Background

    Age and body mass index (BMI) are positively associated with the development of the metabolic syndrome (MetS). Cardiorespiratory fitness (CRF) can attenuate BMI-related increases in prevalence of MetS, but the nature of this association across different age strata has not been fully investigated.

    Aim

    To identify the association between CRF and MetS prevalence across age strata (20–69 years) and determine whether associations are independent of BMI.

    Methods

    CRF was estimated from incremental treadmill exercise in British men attending preventative health screening. Participants were placed in four age strata (20–39, 40–49, 50–59 and 60–69 years) and classified as fit or unfit using age-related cut-offs. The presence of MetS was defined using the National Cholesterol Education Program Adult Treatment Panel III criteria.

    Results

    9666 asymptomatic men (48.7±8.4 years) were enrolled. The prevalence of MetS was 25.5% in all men and ranged from 17.1% in those aged 20–39 years to 30.6% in those aged 60–69 years. Fit men's likelihood of meeting the criteria for MetS was half (OR=0.51, 95% CI 0.46 to 0.57) that of unfit men. The likelihood of MetS was 32–53% lower across age strata in fit, compared with unfit men. Adjustment for BMI attenuated the association, though it remained significant in men aged 20–49 years.

    Conclusions

    The cardiometabolic benefits of CRF are independent of BMI particularly in men <50 years. Public health messages should emphasise the important role of CRF alongside weight management for enhancing cardiometabolic health.




    Kidney function and appropriateness of device therapies in adults with implantable cardioverter defibrillators

    2017-03-13T07:00:47-07:00

    Objective

    Patients with chronic kidney disease (CKD) have higher risk of sudden cardiac death; however, they may not receive implantable cardioverter defibrillators (ICDs), in part due to higher risk of complications. We evaluated whether CKD is associated with greater risk of device-delivered shocks/antitachycardia pacing (ATP) therapies among patients receiving a primary prevention ICD.

    Methods

    We studied participants in the observational Cardiovascular Research Network Longitudinal Study of Implantable Cardioverter Defibrillators. CKD was defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. Outcomes included all delivered shocks/ATPs therapies and type of shock/ATP therapies (inappropriate or appropriate, determined by physician adjudication) within the 3 years. We evaluated the associations between CKD and time to first device therapy, burden of device therapy, and inappropriate versus appropriate device therapy, adjusting for demographics, comorbidity, laboratory values and medication use.

    Results

    Among 2161 participants, 1066 (49.3%) had CKD (eGFR 44±11 mL/min/1.73 m2) at ICD implantation. During mean of 2.26±0.89 years, 9.8% and 18.5% of participants had at least one inappropriate and appropriate shock/ATP therapies, respectively. CKD was not associated with time to first shock/ATP therapies (adjusted HR 0.87, 95% CI 0.73 to 1.05), overall burden of shock/ATP therapies (adjusted relative rate 0.93, 95% CI 0.74 to 1.17) or inappropriate versus appropriate shock/ATP therapies (adjusted relative risk 0.88, 95% CI 0.68 to 1.14) compared with not having CKD.

    Conclusions

    In adults receiving a primary prevention ICD, mild-to-moderate CKD was not associated with the timing, burden or appropriateness of subsequent device therapy. Potential concern for inappropriate ICD-delivered therapies should not preclude ICDs among eligible patients with CKD.




    Graphics and statistics for cardiology: clinical prediction rules

    2017-03-13T07:00:47-07:00

    Graphs and tables are indispensable aids to quantitative research. When developing a clinical prediction rule that is based on a cardiovascular risk score, there are many visual displays that can assist in developing the underlying statistical model, testing the assumptions made in this model, evaluating and presenting the resultant score. All too often, researchers in this field follow formulaic recipes without exploring the issues of model selection and data presentation in a meaningful and thoughtful way. Some ideas on how to use visual displays to make wise decisions and present results that will both inform and attract the reader are given. Ideas are developed, and results tested, using subsets of the data that were used to develop the ASSIGN cardiovascular risk score, as used in Scotland.




    Bleeding associated with the management of acute coronary syndromes

    2017-03-13T07:00:47-07:00

    Learning objectives

  • Enhance understanding with regard to modes of risk stratification alongside consideration of ischaemic versus bleeding sequalae.

  • To demonstrate the prognostic importance of bleeding complications

  • Synthesis of strategies to minimise bleeding complications.

  • Introduction

    Rupture or erosion of a coronary artery atheroma exposes flowing blood to the prothrombotic contents of the plaque, resulting in platelet activation and subsequent thrombus formation. If this process results in reduced coronary blood flow, the patient may present with an acute coronary syndrome (ACS). Total thrombotic occlusion generally results in ST-segment elevation myocardial infarction (STEMI), whereas incomplete occlusion (or extensive collateralisation) is more likely to present as non-STEMI or unstable angina without evidence of myonecrosis (collectively non-ST-segment elevation ACS (NSTE-ACS)). Revascularisation, most commonly with percutaneous coronary intervention (PCI) is standard of care in ACS, as it restores myocardial perfusion by addressing both the thrombotic obstruction and the underlying...




    Cardiovascular highlights from non-cardiology journals

    2017-03-13T07:00:47-07:00

    Continuous positive airway pressure fails to improve cardiovascular outcomes in obstructive sleep apnea

    Obstructive sleep apnea (OSA) is associated with increased cardiovascular events in observational studies. Randomized trials have demonstrated continuous positive airway pressure (CPAP) therapy reduces blood pressure, markers of oxidative stress and insulin insensitivity. Yet, it remains unclear whether treatment with CPAP reduces cardiovascular events. In the largest study of its kind, 2717 patients aged 45 to 75 years with moderate-to-severe OSA and coronary or cerebrovascular disease were randomized in open-label fashion to receive CPAP treatment or usual care alone. The primary composite end point included cardiovascular death, myocardial infarction, stroke and heart failure with secondary end-points including day-time sleepiness, mood and quality of life indices. At a mean follow-up of 3.7 years, the trial was neutral with no difference in the primary end-point between the CPAP (17.0%) and the usual-care groups (15.4%) (p=0.34), and no...




    Inverse prognostic value of post-percutaneous coronary intervention fractional flow reserve in patients with non-ST segment elevation myocardial infarction

    2017-03-13T07:00:47-07:00

    I read with great interest the article by Kasula et al1, and I firmly believe that this is a novel finding and of great clinical significance.

    Utility of fractional flow reserve (FFR) is firmly established in stable coronary artery disease but has been widely debated in patients with acute myocardial infarction (MI) particularly in the culprit vessel.2 3 FFR measurements require maximal coronary hyperaemia, which may be less readily achieved in patients with acute coronary disease because of coronary microvascular dysfunction. This, in turn, may result in a falsely higher FFR value. This will be of particular concern while assessing FFR value post-percutaneous coronary intervention (PCI) since coronary stenting of a ‘hot’ culprit lesion in acute coronary syndrome would inevitably carry risk of some distal embolisation, which may further exacerbate this issue. Since microvascular obstruction carries a poor prognosis, a direct (in contrast...