Sonovue improves endocardial border detection and variability in assessing wall motion score and ejection fraction during stress echocardiography

Background Stress echocardiography is useful for assessing patients with coronary artery disease unable to undergo formal exercise testing. Considerable skill is required to avoid large intra- and inter-observer variability due to poor endocardial definition. Intravenous ultrasound contrast agents are now available which may improve this variability. Aim To study intravenous Sonovue in assessing wall motion score and ejection fraction (EF) during stress echocardiography. Methods Thirty-eight patients undergoing arbutamine stress echocardiography for known or suspected coronary artery disease were studied. Echocardiographic analysis of wall motion score index, endocardial border detection (EBD) and EF was performed at rest and at peak stress before and after intravenous injection of Sonovue, by experienced and inexperienced observers. Results All three observers noted an improvement in endocardial border definition following Sonovue (p=<0.001). At baseline, there was a significant difference in wall motion score index between experienced and inexperienced observers at rest (p=0.01) and at peak stress (p=0.001). Following Sonovue administration this was no longer significant (p=0.07, p=0.114). Intra-observer variability of end diastolic, end systolic volumes (ESV) and EF improved following contrast (p<0.05) at rest and during stress. Conclusion Sonovue significantly improved EBD and reduced intra-observer variability of EF at rest and during peak arbutamine infusion.     

Waist-hip ratio and low HDL predict the risk of coronary artery disease in Pakistanis

OBJECTIVE: To establish risk factor causal associations for coronary artery disease (CAD) in the native Pakistani population. METHODS: We conducted a hospital-based, case-control study of 200 cases with angiographically documented CAD and 200 age- and sex-matched controls without angiographic evidence of CAD. Patients on lipid lowering therapy were excluded. Lifestyle, anthropometric and biochemical risk factors were assessed in both groups. RESULTS: The presence of CAD was associated with current, past or passive smoking, a history of diabetes and high blood pressure, a positive family risk factors in this study; levels were below history of CAD, body fat percentage, waist-hip ratio (WHR), low apolipoprotein A1 or low HDL, lipoprotein (a), glucose, insulin, insulin resistance, C-reactive protein (CRP), total cholesterol to HDL ratio (TC/HDL) and creatinine on univariate conditional logistic regression analysis. In multiple regression analysis, significant independent associations were found with low HDL (OR 0.11; 95% CI 0.04-0.34; p < 0.001) positive family history (OR 1.79; 95% CI 1.09-2.93; p = 0.02), CRP (OR 1.45; 95% CI 1.19-1.75; p < 0.001) and WHR (OR 1.04; 95% CI 1.01-1.08; p = 0.01). Angiograms were also quantified for the extent and severity of CAD by the Gensini scoring system. Quantitative angiographic data showed associations with age (p = 0.01), the duration of diabetes (p = 0.04), WHR (p = 0.06), low HDL (p < 0.001), lipoprotein (a) (p = 0.001), creatinine (p < 0.001) and CRP (p = 0.007). Results indicate that total and LDL cholesterol were not significant currently accepted thresholds for treatment. CONCLUSIONS: The cardiovascular risk profile in this population is consistent with metabolic syndrome where low HDL and WHR can be used to predict the risk of CAD. Results suggest the need to redefine the currently practised approach to CAD management in this population to fit local needs.     

New lipid-lowering agents

Lipid-lowering is established as a proven intervention to reduce atherosclerosis and its complications. This article summarises imminent developments in lipid-lowering therapy, including new statins and cholesterol absorption inhibitors currently undergoing investigation for licensing. It also discusses other therapeutic targets such as squalene synthase, microsomal transfer protein (MTP), acyl-cholesterol acyl transferase (ACAT), cholesterol ester transfer protein (CETP), peroxosimal proliferator activating receptors (PPARs) and lipoprotein (a) (LP(a)), for which compounds have been developed and have at least reached trials in animal models. Lipid-lowering drugs are likely to prove a fast-developing area for novel treatments, as possible synergies exist between new and established compounds for the treatment of atherosclerosis.     

Fibrinogen response with simvastatin versus atorvastatin in familial hypercholesterolemia

The clinical and biochemical determinants of the fibrinogen response to simvastatin or atorvastatin therapy were assessed in 130 patients with severe polygenic or familial hypercholesterolemia treated in a randomized open-trial format design. Hyperfibrinogenemia was associated with atorvastatin, baseline fibrinogen, and initial concentration and change in concentration of apolipoprotein B or low-density lipoprotein cholesterol.     

Combination fibrate-statin therapy for the treatment of severe hypertriglyceridaemia in renal disease

This case report describes the treatment of a patient with end-stage renal disease on peritoneal dialysis who presented with triglycerides of 35 mmol/l, cholesterol of 14 mmol/l and visible chylomicronaemia. She was only partially responsive to statin and fibrate monotherapy, so was treated with fibrate-statin combination therapy. Daily fibrate therapy resulted in a myositis, but once-weekly fibrate therapy with nocturnal daily statin therapy resulted in a reduction in total cholesterol of 49%, triglycerides of 82% and raised HDL by 52%, enabling her to achieve a target LDL of 3 mmol/l and HDL of 1 mmol/l. Combination therapy with low frequency (weekly) fibrate administration and daily statin treatment may provide a means to control the severe hypertriglyceridaemia of patients with renal disease.     

Lipids, cardiovascular disease and atherosclerosis in systemic lupus erythematosus

Systemic lupus erythematosus is commonly associated with early onset cardiovascular disease and is often associated with hyperlipidaemia. This review examines the evidence for an increased prevalence of both CHD and hyperlipidaemia in SLE and mechanisms by which autoimmunity in SLE could accelerate the progression of atheroma. It postulates how lipid lowering therapies used in cardiological disease might help reduce the incidence of CHD in SLE.     

Differing relationships of methylene tetrahydrofolate reductase genotypes with cardiovascular risk in familial and polygenic hypercholesterolaemia

BACKGROUND: Plasma homocysteine and the methylene tetrahydrofolate reductase C677T polymorphism have been suggested as being risk factors for cardiovascular disease. OBJECTIVE: To determine whether plasma homocysteine and the methylene tetrahydrofolate reductase C677T polymorphism are risk factors for coronary heart disease in patients with heterozygous familial hypercholesterolaemia as compared with those with polygenic hyperlipidaemia. METHODS: Plasma homocysteine and the methylene tetrahydrofolate reductase polymorphism were assessed with other risk factors in 112 patients with familial hypercholesterolaemia and 72 patients with polygenic hyperlipidaemia, of whom 29 (25.8%) and 30 (41%) respectively had established cardiovascular disease and in 100 healthy normal subjects. RESULTS: Plasma homocysteine was not significantly elevated in patients with and without coronary heart disease with familial hypercholesterolaemia or polygenic hyperlipidaemia compared with controls. The allele frequencies for C677T were significantly different in patients with coronary heart disease and with polygenic hyperlipidaemia (0.35 versus 0.29) (P = 0.02) as opposed to those with coronary heart disease and familial hypercholesterolaemia (0.25 versus 0.30) (P = 0.63). Methylene tetrahydrofolate reductase genotype but not homocysteine had a weak association with coronary heart disease in logistic regression analysis in patients with polygenic hyperlipidaemia (P = 0.05) but neither methylene tetrahydrofolate reductase genotype or plasma homocysteine was a risk factor in patients with familial hypercholesterolaemia. CONCLUSION: Whilst methylene tetrahydrofolate reductase genotype may be a weak risk factor for coronary heart disease in polygenic hyperlipidaemia as opposed to familial hypercholesterolaemia, homocysteine does not seem to be an important risk factor for coronary heart disease in patients in southern UK.     

Informed Consent

There have been significant changes in the doctor patient relationship with the impact of technology in day-to-day practice. More and more patients are aware of their rights and are keen to make free choice and decision on their treatment. This helps them to choose the treatment of their choice from the options available and to select a physician of their choice. Doctor's decisions are being questioned regarding their correctness and there is a need to educate the patient, on what one offers by way of treatment. In some procedures and types of treatment, patient needs to be educated and informed of the merits and demerits of the treatment available. This will help the patient to make appropriate choice and also to accept some adverse outcome of treatment. Towards this end, all countries are looking afresh at the necessity of Informed Consent. Methods adopted by some countries are highlighted to help our physicians practice them in an appropriate way. A lot of remedial work needs to be done to minimize future litigation, as many doctors misunderstand their legal obligations and haven't caught up with the change in judge's thinking.     

Beta2 integrin/ICAM-1 adhesion molecule interactions in cutaneous inflammation and tumor promotion

The beta2 integrin (CD 18/CD 11 a, b, c) family of proteins mediate adherence of leukocytes to vascular endothelium and the associated ligand, intercellular adhesion molecule-1 (ICAM-1; CD 54), interacts with beta2 integrin proteins to allow transendothelial migration of leukocytes into sites of inflammation. The present study examines the function of these proteins in a murine model of acute cutaneous inflammation induced following topical application of 12-O- tetradecanoylphorbol-13-acetate (TPA) to the dorsal epidermis of SENCAR mice and in a model of skin multistage carcinogenesis. At 24 h following topical application of TPA to the dorsal epidermis of mice, dermal leukocytes expressed higher levels of beta2 integrin protein compared with the lower levels of beta2 integrin protein expression by peripheral blood leukocytes. ICAM-1 protein was localized to epidermal keratinocytes and vascular endothelium in TPA-treated skin and to proliferating papilloma cells. Intravenous (i.v.) injection of either 50 microg anti-beta2 integrin antibody alone or in combination with anti-ICAM-1 antibody significantly inhibited both TPA-stimulated neutrophil infiltration into the dermis (P < 0.001) and myeloperoxidase (MPO) activity (P < 0.03 anti-beta2 integrin antibody; P < 0.01 anti- beta2 integrin + ICAM-1 adhesion molecule antibodies), but had no effect on TPA-induced epidermal hyperplasia. In addition, injection of either anti-ICAM-1 adhesion molecule antibody alone (P < 0.004) or in combination with anti-beta2 integrin antibody (P < 0.001) significantly inhibited TPA-induced production of 7,8-dihydroxy-2'-deoxyguanosine (8- OHdG) immunoreactive proteins by epidermal keratinocytes. Beta2 integrin/ICAM-1 adhesion molecules work in concert to regulate migration, retention and functional activation of leukocytes within the dermis during TPA-induced skin inflammation and within stromal tissue of papillomas that form during multi-stage carcinogenesis. Agents that inhibit these receptor/ligand interactions may be useful in defining the roles of specific cell populations in cutaneous inflammation and multistage carcinogenesis and may also have potential as anti-promoting and anti-progression agents.