Chetan Varma

Current understanding of atherogenesis

Scientific understanding of atherogenesis is constantly developing. From Virchows observations 160 years ago we now recognize the endothelial response to injury as inflammatory, involved in all stages of atherosclerosis. Endothelial activation may cause reversible injury or dysfunction, or lead to irreparable damage. Indeed, early atherosclerosis is reversible. The introduction of genome-wide association testing has furthered the identification of potentially important genetic variants that help explain the heritability of coronary artery disease as well as spontaneous cases of severe coronary artery disease in patients with otherwise minimal risk factors. However, the mechanisms by which many of the newer variants exert their influence remain unknown.

High‐risk myocardial infarction patients appear to derive more mortality benefit from short door‐to‐balloon time than low‐risk patients

Objectives:u2002 To evaluate reduction of door‐to‐balloon (DTB) time and its impact on in‐hospital mortality of high‐risk infarct patients in a collaboration of district general hospitals (DGH) with a physician‐to‐patient model.

Novel concepts of statin therapy for cardiovascular risk reduction in hypertension.

Hypertension is associated with an increase in cardiovascular events. Pathophysiological mechanisms of this include endothelial damage/dysfunction, inflammatory activation, insulin resistance, platelet activation and alterations in the coagulation cascade leading to a prothrombotic state. Dyslipidaemia acts synergistically with hypertension in increasing cardiovascular risk. HMG CoA reductase inhibitors (statins) are lipid-lowering drugs and more recently have been shown to have a significant pleiotropic effect on endothelial function, inflammation, platelet activation and coagulation. Statins affect the whole pathophysiology of atherogenesis from deposition to plaque rupture and thrombogenesis because of its pleiotropic effects. Therefore it is intuitive that statins may be of benefit in hypertensive patients with conventionally normal lipid levels by preventing the pathological effects of hypertension. There is an increasing clinical evidence base for statins use in patients with hypertension. In this article, the novel pleiotropic and conventional mechanisms of statins, and clinical data of statin therapy in patients with hypertension are reviewed.

Traditional Risk Factors for Coronary Atherosclerosis in Indo Asians: The Need for a Reappraisal

Our ability to assess individual patient cardiovascular risk is based on traditional risk factors including patients characteristics (age, sex and body mass index), hypertension, diabetes, smoking, lipid profile and family history of premature coronary disease. These factors are important for the clinician in order to calculate risk and initiate treatment in both primary and secondary settings. As the morbidity and mortality from vascular disease in United Kingdom migrant populations of Indo Asian origin is significantly higher (approximately 50%) than the Western Europeans, an accurate assessment of risk and preventative therapies can reduce cardiovascular risk and improve clinical outcome. Indeed, scoring systems like the Framingham consistently underestimate risk in Indo Asians. This review assesses differences between traditional risk factors in Indo Asians and summarizes the relevance of more novel factors in a more comprehensive evaluation of cardiovascular risk in the Indo Asian population. Greater appreciation of these traditional risk factors for coronary atherosclerosis in Indo Asians--including hypertension and metabolic syndrome (of which hypertension is a key component)--suggests the need for a reappraisal to put these data in context of current management strategies.

Symptom-to-door times in patients presenting with ST elevation myocardial infarction – do ethnic or gender differences exist?

BACKGROUNDnStudies have shown higher in-hospital mortality for female patients and ethnic minorities admitted to hospital with acute ST elevation myocardial infarction (STEMI). Pre-hospital delay is thought to be associated with increased in-hospital mortality.nnnAIMnTo assess the impact of gender and ethnicity on symptom-to-door time (STDT) in patients presenting with STEMI.nnnDESIGNnRetrospective survey of consecutive patients receiving primary percutaneous coronary intervention between January 2008 and January 2013. A multivariate model was used to adjust for confounders.nnnMAIN OUTCOME MEASUREnInfluence of gender and ethnicity on STDT.nnnRESULTSnWe analysed 1020 patients (75% male, 263 South Asians, 38 Afro Caribbeans and 719 White Europeans.) There was a trend towards longer unadjusted median STDT in women compared with men (132u2009min vs. 113u2009min Pu2009=u20090.07) which disappeared after correction for age and ethnicity (Pu2009=u20090.15). There was no gender difference in hospital mortality after correction for age (odds ratio 0.69, 95% confidence interval 0.40-1.18, Pu2009=u20090.17). On linear regression analysis South Asians showed a trend towards longer STDT than other ethnic groups (Pu2009=u20090.08) however after adjustment for diabetes there was no association between South Asian ethnicity and hospital mortality.nnnCONCLUSIONSnNeither female gender nor ethnicity were shown to be associated with significant pre-hospital delay.

Epidemiology and pathogenesis of diffuse obstructive coronary artery disease: the role of arterial stiffness, shear stress, monocyte subsets and circulating microparticles

Abstract Despite falling age-adjusted mortality rates coronary artery disease (CAD) remains the leading cause of death worldwide. Advanced diffuse CAD is becoming an important entity of modern cardiology as more patients with historical revascularisation no longer have suitable anatomy for additional procedures. Advances in the treatment of diffuse obstructive CAD are hampered by a poor understanding of its development. Although the likelihood of developing clinically significant (obstructive) CAD is linked to traditional risk factors, the morphology of obstructive CAD among individuals is highly variable – some patients have diffuse stenotic disease, while others have a focal stenosis. This is challenging to explain in mechanistic terms as vascular endothelium is equally exposed to injury stimulants. Patients with diffuse disease are at high risk of adverse outcomes, particularly if unsuitable for revascularisation. We searched multiple electronic databases (MEDLINE, EMBASE and the Cochrane Database) and reviewed the epidemiology, pathogenesis and prognosis relating to advanced diffuse CAD with particular focus on the role of endothelial shear stress, large artery stiffness, monocyte subsets and circulating microparticles. Key messages Although traditional CAD risk factors correlate strongly with disease severity, significant individual variation in disease morphology exists. Advanced, diffuse CAD is difficult to treat effectively and can significantly impair quality of life and increases mortality. The pathophysiology associated with the progression of CAD is the result of complex maladaptive interaction between the endothelium, cells of the immune system and patterns of blood flow.

Safety and efficacy of abciximab in older adults undergoing percutaneous coronary intervention

As a result of increased cost and bleeding concerns, older patients receive abciximab during percutaneous coronary intervention (PCI) less often than younger patients.

Simultaneous computerised activation of the primary percutaneous coronary intervention pathway reduces out-of-hours door-to-balloon time but not mortality

BACKGROUNDnIn 2009 activation of out of hours (OOH) primary percutaneous coronary intervention (PPCI) in our institution changed from separate telephone calls to a simultaneous computerised alert. We assessed the impact of this protocol change on door-to-balloon (DTB) time, in hospital and 1 year mortality.nnnMETHODSnRetrospective survey of our Myocardial Ischaemia National Audit Project (MINAP) database. OOH patients were categorized--pre- (Group 1) and post- (Group 2) introduction of the computerised alert protocol.nnnRESULTSnOOH PPCI was performed for 793 patients (mean age 61, 73.4% male)--295 in Group 1 and 498 in Group 2. Median DTB times were 92 min (interquartile range [IQR] 75-111) for Group 1 and 76 min (IQR 64-97) for Group 2 (p < 0.0001). Forty-eight percent achieved DTB in ≤ 90 min in Group 1 compared to 70% in Group 2 (p < 0.0001). Computerised alert was associated with a shorter DTB time on multivariate analysis (beta coefficient -0.09, p = 0.03 for linear regression and OR 2.8, 95% CI 1.6-5.0, p < 0.0001 for logistic regression). In hospital mortality was 4.1% in Group 1 and 5% in Group 2 (p = 0.60). All-cause mortality at 1 year was 6.1% in Group 1 and 9.9% in Group 2 (p = 0.09).nnnCONCLUSIONSnSimultaneous computerised activation for OOH PPCI reduced DTB times, increased the number of patients achieving target DTB times but did not affect mortality.