Caroline Morrison

Symptomatic and asymptomatic left-ventricular systolic dysfunction in an urban population

BACKGROUND In most previous epidemiological studies on the prevalence of chronic heart failure (CHF) the disorder has been defined on clinical criteria. In a cross-sectional survey of 2000 men and women aged 25-74, randomly sampled from one geographical area, we assessed left-ventricular systolic function by echocardiography. METHODS 1640 (83%) of those invited took part. They completed a questionnaire on current medication, history, and symptoms of breathlessness. Blood pressure was measured and electrocardiography (ECG) and echocardiography were done. Left-ventricular ejection fraction was measurable in 1467 (89.5%) participants by the biplane Simpsons rate method. FINDINGS The mean left-ventricular ejection fraction was 47.3%. The prevalence of definite left-ventricular systolic dysfunction (defined as a left-ventricular ejection fraction < or = 30%) was 2.9% overall (43 participants); it increased with age and was higher in men than in women (4.0 vs 2.0%). The left-ventricular systolic dysfunction was symptomatic in 1.5% of participants and asymptomatic in 1.4%, 83% of participants with left-ventricular systolic dysfunction had evidence of ischaemic heart disease (IHD) from history or ECG criteria compared with 21% of those without this abnormality (p < 0.001). Hypertension was also more common in those with left-ventricular systolic dysfunction (72 vs 38%, p < 0.001), but there was no difference between those with and without left-ventricular systolic dysfunction in the rate of hypertension without IHD. INTERPRETATION Left-ventricular systolic dysfunction was at least twice as common as symptomatic heart failure defined by clinical criteria. The main risk factors are IHD and hypertension in the presence of IHD; screening of such high-risk groups for left-ventricular systolic dysfunction should be considered.

Randomised controlled trial of specialist nurse intervention in heart failure

Abstract Objectives: To determine whether specialist nurse intervention improves outcome in patients with chronic heart failure. Design: Randomised controlled trial. Setting: Acute medical admissions unit in a teaching hospital. Participants: 165 patients admitted with heart failure due to left ventricular systolic dysfunction. The intervention started before discharge and continued thereafter with home visits for up to 1 year. Main outcome measures: Time to first event analysis of death from all causes or readmission to hospital with worsening heart failure. Results: 31 patients (37%) in the intervention group died or were readmitted with heart failure compared with 45 (53%) in the usual care group (hazard ratio=0.61, 95% confidence interval 0.33 to 0.96).Compared with usual care, patients in the intervention group had fewer readmissions for any reason (86 v 114, P=0.018), fewer admissions for heart failure (19 v 45, P<0.001) and spent fewer days in hospital for heart failure (mean 3.43 v 7.46 days, P=0.0051). Conclusions: Specially trained nurses can improve the outcome of patients admitted to hospital with heart failure. What is already known on this topic Studies have suggested that nurse intervention may reduce readmission in patients with heart failure What this study adds Home based intervention from nurses reduces readmissions for worsening heart failure Regular contact to review treatment and patient education are likely to contribute to this effect

Contribution of modern cardiovascular treatment and risk factor changes to the decline in coronary heart disease mortality in Scotland between 1975 and 1994

OBJECTIVE To estimate the fall in coronary heart disease (CHD) mortality in Scotland attributable to medical and surgical treatments, and risk factor changes, between 1975 and 1994. DESIGN A cohort model combining effectiveness data from meta-analyses with information on treatment uptake in all patient categories in Scotland. SETTING AND PATIENTS The whole Scottish population of 5.1 million, including all patients with recognised CHD. INTERVENTIONS All cardiological, medical, and surgical treatments, and all risk factor changes between 1975 and 1994. Data were obtained from epidemiological surveys, routine National Health Service sources, and local audits. MAIN OUTCOME MEASURES Deaths from CHD in 1975 and 1994. RESULTS There were 15 234 deaths from CHD in 1994, 6205 fewer deaths than expected if there had been no decline from 1975 mortality rates. In 1994, the total number of deaths prevented or postponed by all treatments and risk factor reductions was estimated at 6747 (minimum 4790, maximum 10 695). Forty per cent of this benefit was attributed to treatments (initial treatments for acute myocardial infarction 10%, treatments for hypertension 9%, for secondary prevention 8%, for heart failure 8%, aspirin for angina 2%, coronary artery bypass grafting surgery 2%, and angioplasty 0.1%). Fifty one per cent of the reduction in deaths was attributed to measurable risk factor reductions (smoking 36%, cholesterol 6%, secular fall in blood pressure 6%, and changes in deprivation 3%). Other, unquantified factors apparently accounted for the remaining 9%. These proportions remained relatively consistent across a wide range of assumptions and estimates in a sensitivity analysis. CONCLUSIONS Medical treatments and risk factor changes apparently prevented or postponed about 6750 coronary deaths in Scotland in 1994. Modest gains from individual treatments produced a large cumulative survival benefit. Reductions in major risk factors explained about half the fall in coronary mortality, emphasising the importance and future potential of prevention strategies.

Left ventricular dysfunction, natriuretic peptides, and mortality in an urban population

OBJECTIVE To report the mortality of left ventricular systolic dysfunction (LVD), assessed objectively by echocardiography, and its association with natriuretic peptide hormones in a random sample of 1640 men and women aged 25–74 years from a geographical, urban population. METHODS Left ventricular function was measured by echocardiography in 1640 attendees studied in 1992–3. LVD was defined as a left ventricular ejection fraction (LVEF) ⩽ 30%. Plasma concentrations of N-terminal atrial natriuretic peptide (N-ANP) and brain natriuretic peptide (BNP) were measured by standard radioimmunoassays. Mortality was documented at four years. RESULTS The four year all cause mortality rate in the whole cohort was 4.9% (80 deaths). It was 21% (nine deaths) in those with an LVEF ⩽ 30% and 4% in those whose LVEF was > 30% (p < 0.001). The median (interquartile range) BNP concentration in those who died was 16.9 pg/ml (8.8–27) and 7.8 pg/ml (3.4–13) in survivors (p < 0.0001). Similarly, N-ANP had a median concentration of 2.35 ng/ml (1.32–3.36) in those with a fatal outcome and 1.27 ng/ml (0.9–2.0) in those alive at four years (p < 0.0001). Subjects with an LVEF ⩽ 40% also had a significant mortality rate of 17% if they also had a BNP concentration ⩾ 17.9 pg/ml compared with 6.8% if their BNP was below this concentration (p = 0.013). Multivariate analysis revealed the independent predictors of four year all cause mortality to be increasing age (p < 0.001), a BNP concentration ⩾ 17.9 pg/ml (p = 0.006), the presence of ischaemic heart disease (p = 0.03), and male sex (p = 0.04). CONCLUSIONS LVD is associated with a considerable mortality rate in this population. BNP also independently predicts outcome. In addition to its role as a diagnostic aid in chronic heart failure and LVD, it provides prognostic information and clarifies the meaning of a given degree of LVD.

In-Depth Haplotype Analysis of ABCA1 Gene Polymorphisms in Relation to Plasma ApoA1 Levels and Myocardial Infarction

Objective—By regulating the cellular cholesterol efflux from peripheral cells to high-density lipoprotein, the ABCA1 protein is suspected to play a key role in lipid homeostasis and atherosclerosis. Twenty-six polymorphisms of the ABCA1 gene were genotyped and tested for association with plasma levels of ApoA1 and myocardial infarction (MI) in the ECTIM study. Methods and Results—In addition to single-locus analysis, a systematic exploration of all possible haplotype effects was performed, with this exploration being performed on a minimal set of “tag” polymorphisms that define the haplotype structure of the gene. Two polymorphisms were associated with plasma levels of ApoA1, 1 in the promoter (C-564T) and 1 in the coding (R1587K) regions, whereas only 1 polymorphism (R219K) was associated with the risk of MI. However, no haplotype effect was detected on ApoA1 variability or on the risk of MI. Conclusion—ABCA1 gene polymorphisms but not haplotypes are involved in the variability of plasma ApoA1 and the susceptibility to coronary artery disease.

Polymorphisms of the 2 -adrenoceptor (ADRB2) gene and essential hypertension: the ECTIM and PEGASE studies

Objectives The β2-adrenoceptor (ADRB2) plays a pivotal role in signalling in relation to hypertension and obesity. Polymorphisms of the ADRB2 gene have been shown to be potentially related to essential hypertension and other non-cardiovascular disease phenotypes. We investigated whether genetic variation of the ADRB2 gene might be related to essential hypertension or myocardial infarction (MI). Methods Four ADRB2 gene polymorphisms C19R (T−47C), T−20C, G16R (G+46A), Q27E (C+79G) were investigated in two studies: PEGASE, a study of moderate to severe hypertension (707 cases) conducted in France, and ECTIM, a case-control study of MI (1178 cases, 1187 controls) conducted in France, Northern Ireland and Scotland. Genotyping was performed using allele-specific oligonucleotides. Results The ADRB2 polymorphisms T−20C and Q27E were found to be completely concordant, generating the haplotypes [T−20–Q27] and [C−20–E27]. Three main haplotypes accounted for 94% of all haplotypes: [R19–G16–E27] (39%), [C19–R16–Q27] (35%) and [C19–G16–Q27] (20%). Haplotype frequencies were not significantly different between countries. Allele and genotype frequencies did not differ significantly between cases with essential hypertension or MI and control subjects. There was no association of the polymorphisms with early onset hypertension, blood pressure level, coronary artery stenosis or any other phenotype measured in these study populations. In the ECTIM Study, our calculation revealed that we could have detected an odds ratio (OR) for MI of 1.3 with 80% power at a 5% type I error probability, the corresponding value for the PEGASE Study being an OR of 1.6 for hypertension. Conclusions From our present analysis we conclude that the ADRB2 gene polymorphisms studied do not contribute in any important way to the risk of essential hypertension or MI in subjects of European ancestry.

Association studies between haemochromatosis gene mutations and the risk of cardiovascular diseases

Background Haemochromatosis is a common genetic disorder, inherited as an autosomal recessive trait that results in a progressive accumulation of iron in most tissues of the body. Positive association studies have been recently published between cardiovascular diseases and heterozygosity for the major mutation C282Y in the haemochromatosis gene HFE.

Overcoming barriers to engaging socio-economically disadvantaged populations in CHD primary prevention: a qualitative study.

BackgroundPreventative medicine has become increasingly important in efforts to reduce the burden of chronic disease in industrialised countries. However, interventions that fail to recruit socio-economically representative samples may widen existing health inequalities. This paper explores the barriers and facilitators to engaging a socio-economically disadvantaged (SED) population in primary prevention for coronary heart disease (CHD).MethodsThe primary prevention element of Have a Heart Paisley (HaHP) offered risk screening to all eligible individuals. The programme employed two approaches to engaging with the community: a) a social marketing campaign and b) a community development project adopting primarily face-to-face canvassing. Individuals living in areas of SED were under-recruited via the social marketing approach, but successfully recruited via face-to-face canvassing. This paper reports on focus group discussions with participants, exploring their perceptions about and experiences of both approaches.ResultsVarious reasons were identified for low uptake of risk screening amongst individuals living in areas of high SED in response to the social marketing campaign and a number of ways in which the face-to-face canvassing approach overcame these barriers were identified. These have been categorised into four main themes: (1) processes of engagement; (2) issues of understanding; (3) design of the screening service and (4) the priority accorded to screening. The most immediate barriers to recruitment were the invitation letter, which often failed to reach its target, and the general distrust of postal correspondence. In contrast, participants were positive about the face-to-face canvassing approach. Participants expressed a lack of knowledge and understanding about CHD and their risk of developing it and felt there was a lack of clarity in the information provided in the mailing in terms of the process and value of screening. In contrast, direct face-to-face contact meant that outreach workers could explain what to expect. Participants felt that the procedure for uptake of screening was demanding and inflexible, but that the drop-in sessions employed by the community development project had a major impact on recruitment and retention.ConclusionSocio-economically disadvantaged individuals can be hard-to-reach; engagement requires strategies tailored to the needs of the target population rather than a population-wide approach.

Polymorphism R92Q of the tumour necrosis factor receptor 1 gene is associated with myocardial infarction and carotid intima-media thickness - the ECTIM, AXA, EVA and GENIC studies

The TNFRSF1A gene was screened for polymorphisms in 95 subjects with premature myocardial infarction (MI), who also had one parent who had an MI. A total of 10 polymorphisms were found: three in the promoter region, two in exons and five in introns. All polymorphisms were genotyped in ECTIM, a case–control study of MI (1815 subjects). The nonsynonymous 92Q allele was found in 1.8, 1.0 and 1.7% of controls from Strasbourg, Belfast and Glasgow – respectively; in cases: 4.2, 2.2 and 3.2%. The population-adjusted odds ratio (OR) for MI associated with allele Q carrying was 2.15 (95% CI: 1.09–4.23). To check its possible implication in atherosclerosis, this polymorphism was then genotyped in the AXA Study (ultrasound examinations of carotid and femoral arteries in the context of an employment medical examination, 733 subjects), the EVA Study (ultrasound examinations of carotid arteries in a study of cognitive and vascular ageing, 1092 subjects) and the GENIC Study (on brain infarction (BI), 912 subjects). In the AXA Study, among smokers, carrying the 92Q allele was positively associated with the presence of a carotid plaque (OR 5.07; 95% CI: 1.64–15.63) and with a thickening of the carotid intima-media thickness (IMT) (0.59 (0.11) vs 0.54 (0.11), P=0.045). In the EVA Study, carriers of allele 92Q had an increased mean carotid IMT (0.70 (0.09) vs 0.67 (0.13), P=0.02). No significant association of the 92Q allele was found with BI in the GENIC Study. Overall, these results may suggest that carriers of the 92Q allele may be at increased risk of atherosclerosis.

Haplotypes of the Caspase-1 Gene, Plasma Caspase-1 Levels, and Cardiovascular Risk

Caspase-1 processes the interleukin (IL)-1&bgr; and IL-18 inactive precursors to the biologically active cytokines that are known to have proatherogenic effects. The present study investigated the genetic variability of the CASP1 gene and plasma levels of caspase-1 in relation to cardiovascular risk. In Europeans, 3 tag SNPs captured 4 common haplotypes of the CASP1 gene. Among these, the Ain6 allele of the G+7/in6A polymorphism was less frequent in 246 cases with myocardial infarction and a parental history of disease than in 253 controls free of familial history of disease (0.13±0.02 versus 0.20±0.02; P=0.005). However, in a larger case/control study (n=1774), these effects are borderline restricted to the UK population. In a prospective cohort of 1168 patients with coronary artery disease followed up during a median period of 6.0 years, the Ain6 allele exhibited a borderline association with future cardiovascular death (hazard ratio [HR]: 0.64, 0.41 to 1.01; P=0.053) and was associated with lower serum IL-18 levels (P=0.014). Baseline caspase-1 levels in the top quartile of the distribution were predictive of cardiovascular deaths (HR=3.62, 1.81 to 7.27; P=0.0003 compared with the bottom quartile). Finally, in vitro assays of allelic imbalance showed that the CASP1 haplotype carrying the Ain6 allele was associated with a lower mRNA expression. These results indicate that caspase-1 levels are predictive of future cardiovascular death in patients with coronary artery disease. The role of CASP1 genetic variations in the susceptibility to myocardial infarction requires further investigation.