Chromosome 9p21.3 is associated with early-onset coronary heart disease in the Irish population

Coronary heart disease (CHD) remains a leading cause of death across the world. A region on chromosome 9p21.3 has been recently reported to be associated with CHD. We evaluated 3 SNPs and 3 common haplotypes in the 9p21.3 region in 1494 individuals from 580 Irish families, where at least 1 member had early-onset (males

Identifying strategies to maximise recruitment and retention of practices and patients in a multicentre randomised controlled trial of an intervention to optimise secondary prevention for coronary heart disease in primary care.

Background Recruitment and retention of patients and healthcare providers in randomised controlled trials (RCTs) is important in order to determine the effectiveness of interventions. However, failure to achieve recruitment targets is common and reasons why a particular recruitment strategy works for one study and not another remain unclear. We sought to describe a strategy used in a multicentre RCT in primary care, to report researchers’ and participants’ experiences of its implementation and to inform future strategies to maximise recruitment and retention. Methods In total 48 general practices and 903 patients were recruited from three different areas of Ireland to a RCT of an intervention designed to optimise secondary prevention of coronary heart disease. The recruitment process involved telephoning practices, posting information, visiting practices, identifying potential participants, posting invitations and obtaining consent. Retention involved patients attending reviews and responding to questionnaires and practices facilitating data collection. Results We achieved high retention rates for practices (100%) and for patients (85%) over an 18-month intervention period. Pilot work, knowledge of the setting, awareness of change in staff and organisation amongst participant sites, rapid responses to queries and acknowledgement of practitioners’ contributions were identified as being important. Minor variations in protocol and research support helped to meet varied, complex and changing individual needs of practitioners and patients and encouraged retention in the trial. A collaborative relationship between researcher and practice staff which required time to develop was perceived as vital for both recruitment and retention. Conclusions Recruiting and retaining the numbers of practices and patients estimated as required to provide findings with adequate power contributes to increased confidence in the validity and generalisability of RCT results. A continuous dynamic process of monitoring progress within trials and tailoring strategies to particular circumstances, whilst not compromising trial protocols, should allow maximal recruitment and retention.

Using the opinions of coronary heart disease patients in designing a health education booklet for use in general practice consultations.

Objective This study explored how coronary heart disease (CHD) patients’ views would inform the design of an information booklet aimed at providing patients and practitioners with a resource to help influence positively patients’ health behaviour outcomes. Methods Opinions of patients (N=23) with CHD about their information needs, particularly lifestyle advice, were explored using a qualitative approach in four general practices. This information was used in designing a booklet for a pilot study intervention aimed at promoting healthy lifestyle behaviours and medication adherence among people with CHD. Subsequent focus groups explored patients’ (N=17) opinions about the booklet’s ‘fitness for purpose’; semi-structured interviews with practitioners (N=10) examined their views on the booklet’s usefulness. Results In initial focus groups patients identified gaps in their information provision regarding coping with stress, available local community support and medication purpose. A booklet, prepared on the basis of previous literature, was modified to address these gaps. Pilot study patients were satisfied with the re-designed booklet and practitioners reported that its use in consultations enabled change implementation and facilitated patients’ understanding of connections between lifestyle and health outcomes. Conclusion Acknowledging the opinions of CHD patients in producing health information booklets which emphasised a patient centred approach supported practitioner-patient partnerships for choosing healthy lifestyle choices.

Rho kinase and protein kinase C involvement in vascular smooth muscle myofilament calcium sensitization in arteries from diabetic rats.

BACKGROUND AND PURPOSE: Diabetes mellitus (DM) causes multiple dysfunctions including circulatory disorders such as cardiomyopathy, angiopathy, atherosclerosis and arterial hypertension. Rho kinase (ROCK) and protein kinase C (PKC) regulate vascular smooth muscle (VSM) Ca(2+) sensitivity, thus enhancing VSM contraction, and up-regulation of both enzymes in DM is well known. We postulated that in DM, Ca(2+) sensitization occurs in diabetic arteries due to increased ROCK and/or PKC activity. EXPERIMENTAL APPROACH: Rats were rendered hyperglycaemic by i.p. injection of streptozotocin. Age-matched control tissues were used for comparison. Contractile responses to phenylephrine (Phe) and different Ca(2+) concentrations were recorded, respectively, from intact and chemically permeabilized vascular rings from aorta, tail and mesenteric arteries. KEY RESULTS: Diabetic tail and mesenteric arteries demonstrated markedly enhanced sensitivity to Phe while these changes were not observed in aorta. The ROCK inhibitor HA1077, but not the PKC inhibitor chelerythrine, caused significant reduction in sensitivity to agonist in diabetic vessels. Similar changes were observed for myofilament Ca(2+) sensitivity, which was again enhanced in DM in tail and mesenteric arteries, but not in aorta, and could be reduced by both the ROCK and PKC blockers. CONCLUSIONS AND IMPLICATIONS: We conclude that in DM enhanced myofilament Ca(2+) sensitivity is mainly manifested in muscular-type blood vessels and thus likely to contribute to the development of hypertension. Both PKC and, in particular, ROCK are involved in this phenomenon. This highlights their potential usefulness as drug targets in the pharmacological management of DM-associated vascular dysfunction.