Caroline Daly

Guidelines on the management of stable angina pectoris: executive summary

We thank the authors for raising the interesting discussion regarding the treatment of hypertension in patients with concomitant coronary disease. The J-shaped association between on-treatment blood pressure and risk has been described in longitudinal cohorts of patients with treated hypertension as well as in clinical trial populations, both in on-treatment and control arms. However, it is not absolutely clear that the association is treatmentrelated; in fact, one meta-analysis of seven randomized controlled trials including data on more than 40 000 patients has shown that the J-shaped relationship between blood pressure and mortality was not related to antihypertensive treatment. In this meta-analysis, noncardiovascular death was inversely related to blood pressure (both systolic and diastolic) in contrast to the J-shaped relationships for cardiovascular and total mortality, leading the authors to hypothesize that poor health conditions leading to low blood pressure and an increased risk of death might in part explain the J-shaped curve. Secondly, as discussed in the full-text version of the guidelines, there is accumulating evidence that blood pressure lowering in the ‘normal’ range is associated with improved cardiovascular outcomes in the population with known coronary disease. In the CAMELOT study, patients with coronary disease and mean blood pressure of 129/78 were randomized to enalapril, amlodipine, or placebo. Blood pressure reductions were similar (5/2 mm) in both treatment groups and associated with similar relative reductions in the composite endpoint of cardiovascular death, MI, and stroke, although not statistically significant in either group because of the small sample size. An intravascular ultrasound substudy demonstrated a significant inverse correlation between progression of atherosclerosis and blood pressure reduction even in this normal blood pressure range, with the greatest benefit observed in patients whose blood pressure fell below 120/80. Thus, the task force has felt it important, in the absence of unequivocal evidence to the contrary, to preserve consistency between guidelines on prevention and angina with regard to targets for institution of therapy for hypertension in the presence of coronary disease. No lower limit has yet been identified as a definite cutoff beyond which blood pressure should not be lowered further, although, clearly, symptomatic hypotension or postural hypotension will limit aggressive blood pressure lowering in the lower range.

Gender Differences in the Management and Clinical Outcome of Stable Angina

Background— We sought to examine the impact of gender on the investigation and subsequent management of stable angina and to assess gender differences in clinical outcome at 1 year. Methods and Results— The Euro Heart Survey of Stable Angina enrolled patients with a clinical diagnosis of stable angina on initial assessment by a cardiologist. Baseline clinical details and cardiac investigations planned or performed within a 4-week period of the assessment were recorded, and follow-up data were collected at 1 year. A total of 3779 patients were included in the survey; 42% were female. Women were less likely to undergo an exercise ECG (odds ratio, 0.81; 95% CI, 0.69 to 0.95) and less likely to be referred for coronary angiography (odds ratio, 0.59; 95% CI, 0.48 to 0.72). Antiplatelet and statin therapies were used significantly less in women than in men, both at initial assessment and at 1 year, even in those in whom coronary disease had been confirmed. Women with confirmed coronary disease were less likely to be revascularized than their male counterparts and were twice as likely to suffer death or nonfatal myocardial infarction during the 1-year follow-up period (hazard ratio, 2.09; 95% CI, 1.13 to 3.85), even after multivariable adjustment for age, abnormal ventricular function, severity of coronary disease, and diabetes. Conclusions— Significant gender bias has been identified in the use of investigations and evidence-based medical therapy in stable angina. Women were also less likely to be revascularized. The observed bias is of particular concern in light of the adverse prognosis observed among women with stable angina and confirmed coronary disease.

Silent Myocardial Ischemia

Silent myocardial ischemia has emerged from a subject of mainly research interest to one with important clinical implications for practicing physicians. Although the pathophysiologic mechanisms responsible for the absence of pain are still not clear, it is apparent that episodes of silent myocardial ischemia are frequent and occur in many patients with coronary artery disease; episodes occur both in asymptomatic and symptomatic patients; episodes are detectable by various noninvasive and invasive techniques; and episodes appear to have important prognostic implications when combined with the extent of anatomic disease and degree of left ventricular dysfunction. It is expected the rapidly accumulating prognostic data, especially in patients after infarctions and patients with unstable angina, will have a profound effect on the way physicians treat their patients with coronary artery disease.

Predicting prognosis in stable angina—results from the Euro heart survey of stable angina: prospective observational study

Abstract Objectives To investigate the prognosis associated with stable angina in a contemporary population as seen in clinical practice, to identify the key prognostic features, and from this to construct a simple score to assist risk prediction. Design Prospective observational cohort study. Setting Pan-European survey in 156 outpatient cardiology clinics. Participants 3031 patients were included on the basis of a new clinical diagnosis by a cardiologist of stable angina with follow-up at one year. Main outcome measure Death or non-fatal myocardial infarction. Results The rate of death and non-fatal myocardial infarction in the first year was 2.3 per 100 patient years; the rate was 3.9 per 100 patient years in the subgroup (n = 994) with angiographic confirmation of coronary disease. The clinical and investigative factors most predictive of adverse outcome were comorbidity, diabetes, shorter duration of symptoms, increasing severity of symptoms, abnormal ventricular function, resting electrocardiogaphic changes, or not having any stress test done. Results of non-invasive stress tests did not significantly predict outcome in the population who had tests done. A score was constructed using the parameters predictive of outcome to estimate the probability of death or myocardial infarction within one year of presentation with stable angina. Conclusions A score based on the presence of simple, objective clinical and investigative variables makes it possible to discriminate effectively between very low risk and very high risk patients and to estimate the probability of death or non-fatal myocardial infarction over one year.

Adverse prognosis associated with the metabolic syndrome in established coronary artery disease: Data from the EUROPA trial

Objective: To assess the prevalence of metabolic syndrome, and its effect on cardiovascular morbidity and mortality in patients with established coronary disease and to explore the inter-relationships between metabolic syndrome, diabetes, obesity and cardiovascular risk. Methods: The presence of metabolic syndrome was determined in 8397 patients with stable coronary disease from the European Trial on Reduction of Cardiac Events with Perindopril in Stable Coronary Artery Disease, with mean follow-up of 4.2 years. Metabolic syndrome was defined using a modified version of the National Cholesterol Education Programme criteria. Results: Metabolic syndrome was present in 1964/8397 (23.4%) of the population and significantly predicted outcome; relative risk (RR) of cardiovascular mortality  =  1.82 (95% CI 1.40 to 2.39); and fatal and non-fatal myocardial infarction RR = 1.50 (95% CI 1.24 to 1.80). The association with adverse outcomes remained significant after adjustment, RR of cardiovascular mortality after adjustment for conventional risks and diabetes  =  1.39 (95% CI 1.03 to 1.86). In comparison with normal weight subjects without diabetes or metabolic syndrome, normal weight dysmetabolic subjects (with either diabetes or metabolic syndrome) were at substantially increased risk of cardiovascular death (RR = 4.05 (95% CI 2.38 to 6.89)). The relative risks of cardiovascular death for overweight and obese patients with dysmetabolic status were nominally lower (RR = 3.01 (95% CI 1.94 to 4.69) and RR = 2.35 (95% CI 1.50 to 3.68), respectively). Conclusions: Metabolic syndrome is associated with adverse cardiovascular outcome, independently of its associations with diabetes and obesity. A metabolic profile should form part of the risk assessment in all patients with coronary disease, not just those who are obese.

Inadequate control of heart rate in patients with stable angina: results from the European heart survey.

Aims To examine resting heart rate (HR) in a population presenting with stable angina in relation to prior and subsequent pharmacological treatment, comorbid conditions and clinical outcome. Methods and results The European Heart Survey was a prospective, observational, cohort study of 3779 patients with stable angina newly presenting to cardiology services. Mean baseline resting HR was 73 beats/min (bpm) and 52.3% of patients had a baseline HR > 70 bpm. Over half of patients were on no chronotropic medication at baseline. Patients with chronic respiratory disease or diabetes had higher resting HRs (75–76 bpm), and were more likely to have been receiving calcium channel blockers at baseline assessment. Overall, β-blockers were the most common treatment administered following cardiologist assessment, but were used less frequently in patients with chronic respiratory disease and diabetes, and the dosages used were less than that found to be effective in clinical trials. Mean daily doses of metoprolol, bisoprolol, carvedilol, and atenolol were 75 mg, 6 mg, 19 mg and 55 mg, respectively. Higher HR at baseline was associated with higher rates of cardiovascular mortality and hospitalisation for heart failure. Conclusion Control of ischaemic symptoms through heart rate modification in patients with angina is currently inadequate, both by primary referring physicians and cardiologists. Given the adverse outcome associated with higher resting heart rates in this as in other studies, and the availability of specific HR reducing strategies, attention should be given to achieving optimal HR control.

Guía sobre el manejo de la angina estable. Versión resumida

Preámbulo . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 920 Introducción . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 921 Definición y fisiopatología . . . . . . . . . . . . . . . . . . 921 Epidemiología . . . . . . . . . . . . . . . . . . . . . . . . . . . . 921 Historia natural y pronóstico . . . . . . . . . . . . . . . . . 921 Diagnóstico y valoración . . . . . . . . . . . . . . . . . . . 922 Síntomas y signos . . . . . . . . . . . . . . . . . . . . . . . 922 Pruebas de laboratorio . . . . . . . . . . . . . . . . . . 924 Radiografía de tórax . . . . . . . . . . . . . . . . . . . 925 Investigaciones cardiacas no invasivas . . . . . . . . 925 ECG en reposo . . . . . . . . . . . . . . . . . . . . . . . . . 925 ECG de esfuerzo . . . . . . . . . . . . . . . . . . . . . . . . 926 Prueba de esfuerzo combinada con técnicas de imagen . . . . . . . . . . . . . . . . . . . . . . . . . . . 927 Ecocardiografía en reposo . . . . . . . . . . . . . . . . 930 Técnicas no invasivas para la valoración de la calcificación y la anatomía coronarias . . . . 930 Técnicas invasivas para la evaluación de la anatomía coronaria . . . . . . . . . . . . . . . . . . 931 Angiografía coronaria . . . . . . . . . . . . . . . . . . . . . . 931 Estratificación del riesgo . . . . . . . . . . . . . . . . . . . . 931 Estratificación del riesgo mediante evaluación clínica . . . . . . . . . . . . . . . . . . . . . 932 Estratificación del riesgo mediante la prueba de esfuerzo . . . . . . . . . . . . . . . . . . . . . . . . . . 933 Estratificación del riesgo mediante la función ventricular . . . . . . . . . . . . . . . . . . . . . . . . . . . 935 Estratificación del riesgo mediante angiografía coronaria . . . . . . . . . . . . . . . . . . 936 Consideraciones diagnósticas especiales: angina con arterias coronarias «normales» . . . . . . . . . . 936 Síndrome X . . . . . . . . . . . . . . . . . . . . . . . . . . . . 937 Diagnóstico del síndrome X . . . . . . . . . . . . . . . 939 Angina vasoespástica/variante . . . . . . . . . . . . . 939 Tratamiento . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 940 Objetivos del tratamiento . . . . . . . . . . . . . . . . . 940 Manejo general . . . . . . . . . . . . . . . . . . . . . . . . . 940 Hipertensión, diabetes y otras alteraciones . . . . 941 Actividad sexual . . . . . . . . . . . . . . . . . . . . . . . . 941 Tratamiento farmacológico de la angina estable . . 941 Tratamiento farmacológico para mejorar el pronóstico . . . . . . . . . . . . . . . . . . . . . . . . . 941 Tratamiento farmacológico de los síntomas y la isquemia . . . . . . . . . . . . . . . . . . . . . . . . . 946 Consideraciones terapéuticas especiales: síndrome X y la angina vasoespástica . . . . 950 Revascularización miocárdica . . . . . . . . . . . . . . . . 951 Guía sobre el manejo de la angina estable. Versión resumida

Natriuretic peptides in the diagnosis of heart disease--first amongst equals?

The natriuretic peptides and their role in neurohumoral regulation of the cardiovascular system have become the focus of considerable interest from the scientific and clinical community in recent years. BNP in particular has been shown to be an important diagnostic and prognostic marker of use in a wide range of applications. As measurement techniques develop and are refined, routine evaluation of serum levels of these markers is expected to become more widespread. We have reviewed the biochemistry of the natriuretic peptide family, their role in cardiovascular pathophysiology and the evidence supporting their use in the clinical setting.

The Initial Management of Stable Angina in Europe, From the Euro Heart Survey

AIMS In order to assess adherence to guidelines and international variability in management, the Euro Heart Survey of Newly Presenting Angina prospectively studied medical therapy, percutaneous coronary intervention (PCI), and surgery in patients with new-onset stable angina in Europe. METHODS AND RESULTS Consecutive patients, 3779 in total, with a clinical diagnosis of stable angina by a cardiologist were enrolled. After initial assessment by a cardiologist, 78% were treated with aspirin, 48% with a statin, and 67% with a beta-blocker. ACE-inhibitors were prescribed by the cardiologist in 37% overall. Revascularization rates were low, with only 501 (13%) patients having PCI or coronary bypass surgery performed or planned. However, when restricted to patients with coronary disease documented within 4 weeks of assessment, over 50% had revascularization performed or planned. Among other factors, the national rate of angiography and availability of invasive facilities significantly predicted the likelihood of revascularization, OR 2.4 and 2.0, respectively. CONCLUSION This survey shows a shortfall between guidelines and practice with regard to the use of evidence-based drug therapy and evidence that revascularization rates are strongly influenced by non-clinical, in addition to clinical, factors.