Developing the utility of blood biomarker associations beyond population sample linkage to events in cardiovascular patients.

West et al.¹ report a small, well designed post hoc nested case–controlsample from the LIPID trial of pravastatin.² This was completedin low risk subjects with documented coronary disease in theform of a previous confirmed acute coronary syndrome (ACS).This additional report examines biomarker linkage over a relativelyshort time frame of 2–3 years and highlights two measurementsperhaps not intuitively linked to the biology of coronary diseaseprogression. The conditional logistic regression analysis showsa significant linkage association following point analysis forN-terminal brain natriuretic peptide (NT-BNP) and tissue metalloproteinase-1(TIMP-1). TIMP-1 has been linked to cardiovascular events inlow risk patients previously, in patients with less well confirmedcoronary disease.³ Its re-affirmation     

Adiponectin and risk of acute coronary syndromes: defining the obesity phenotype.

Obesity is a major risk factor for coronary heart disease (CHD),the leading cause of death worldwide.¹ Acute coronary syndromes(ACS), including unstable angina pectoris and myocardial infarction,usually result from acute coronary thrombosis as a product ofatherosclerotic CHD. There is no straightforward relationshipbetween plaque size and likelihood of plaque rupture, and angiographicstudies have shown that lesions preceding non-fatal acute eventsare usually not haemodynamically significant.² Further, themajority of ruptured plaques heals without clinical consequence.Understanding the pathophysiology that leads to CHD in generaland to ACS specifically and identifying the risk factors arecrucial steps for efforts to prevent these diseases. Obese individualshave an ~1.5–2.0-fold increased risk for CHD, and between15 and 20% of all cases of CHD can be attributed     

Exercise testing post-MI: still worthwhile in the interventional era

Valeur et al.¹ report findings from a substudy of the DANAMI-2trial. The paper describes the prognostic importance of a pre-dischargemaximal exercise test following acute myocardial infarctionin the era of aggressive reperfusion treatment of ST-elevationmyocardial infarction (STEMI). Exercise testing has been validated and adopted for risk stratificationbefore discharge in patients with acute coronary syndromes forseveral years.^2,3 In addition to providing important prognosticinformation, exercise testing has also been used to select high-riskpatients with provocable myocardial ischaemia (MI) suitablefor revascularization.⁴ A pre-discharge exercise test also hassignificant impact on     

The role of infection in cardiovascular disease: more support but many questions remain.

The study by Madjid et al. is a valuable addition to the evidencesupporting a role for infections in cardiovascular disease.Capitalizing on the very high rate of autopsies that are routinelyperformed in St Petersburg and the availability of high qualitydata about circulating levels of influenza infection, a clearassociation between influenza epidemics and increased ratesof deaths from coronary heart disease was demonstrated. Theassociation may not, of course, be causal. Ambient cold temperaturesare likely to have been closely associated with levels of influenza,and could well have contributed to the effect on coronary deathobserved, particularly given the setting of northern Russia.However, the study by Madjid et al.¹ does provide further supportfor a role of infection in triggering acute vascular events.A sharp     

The study of diastole by tagged MRI: are we nearly there yet?

This editorial refers to "Persistent diastolic dysfunction despitecomplete systolic functional recovery after reperfused acutemyocardial infarction demonstrated by tagged magnetic resonanceimaging" by C.F. Azevedo et al. on page 1419 Over the last 15 years, tagged magnetic resonance imaging (MRI)of the heart has emerged as an accurate non-invasive techniquethat provides detailed quantitative assessment of myocardialstrain or deformation.^1,2 In particular, it has been used toprecisely characterise regional systolic intrinsic contractilityof the left ventricle (LV) in experimental models of acute myocardialischaemia³ and in patients with coronary artery disease.⁴ Recently,for the detection of myocardial ischaemia during pharmacologicalstress testing, the superiority of tagged MRI     

Is there a gender paradox in the early invasive strategy for non ST-segment elevation acute coronary syndromes?

This editorial refers to "Do men benefit more than women from aninterventional strategy in patients with unstable angina or non-ST-elevationmyocardial infarction? The impact of gender in the RITA 3 trial".by T.C. Clayton on page 1641 Coronary artery disease and, in particular, acute coronary syndromes(ACS), is the leading cause of mortality and morbidity in industrialisednations.¹ While major advances in the diagnosis and treatmentof ACS, both in terms of pharmacotherapy and catheter-basedrevascularisation, have resulted in a continuing, steady decreasein coronary heart disease (CHD) mortality over the last decadeamong men, the cardiovascular event rate among women has eitherlevelled off or increased – especially in older age groupsand among various ethnic minorities.^2–4 One of these advances, percutaneous coronary intervention (PCI),has become a standard treatment option for many patients –both men and women – with     

Acute haemodynamic and myocardial metabolic effects of intravenous urapidil in severe heart failure

The acute haemodynamic and myocardial metabolic effects of intravenousurapadil were evaluated in 12 patients with severe congestiveheart failure due to coronary heart disease. Urapidil was givenintravenously (0.5 mg kg^–1 min^–1 as a bolus) followedby infusion at a rate of 4 µg kg^–1 min^–1 for120 min. Following urapidil administration, cardiac index increasedby 29%, mean pulmonary artery wedge pressure fell by 35% andsystemic vascular resistance by 33%. The fall in mean arterialpressure was moderate. No significant alterations in coronarysinus blood flow, myocardial oxygen consumption and myocardiallactate extraction occurred. No untoward effect was observed.This study shows that intravenous urapidil produces beneficialhaemodynamic effects without a deleterious effect on myocardialmetabolism in patients with heart failure due to coronary heartdisease.     

In search of the grail: the never-ending story of biomarkers for coronary risk prediction.

This editorial refers to "Association between differential leucocytecount and incident coronary heart disease: 1764 incident casesfrom seven prospective studies of 30000 individuals"¹ by J.G.Wheeler et al. on page 1287

"I was brought up in an older tradition. I was told: "beforeordering a test decide what you will do if it is (a) positive,or (b) negative, and if both answers are the same don't do thetest. At the other end of the scale is the most recent innovationwhereby a package of results of a dozen tests arrive at thebedside almost before the signs and symptoms have been elicited"A. Cochrane. Effectiveness and efficiency, p. 43.

The leukocyte has been recognised as a principal effector cellin the acute inflammatory reaction since the end of the 19thcentury.¹ Circulating leukocytes, especially the     

Pregnancy associated plasma protein-A and coronary atherosclerosis: marker, friend, or foe?

The natural history of coronary artery disease is complex andis characterized by the central role played by inflammation.Atherogenic stimuli, such as oxidized lipoproteins, glycationend products, hypertension, and smoking, cause endothelial dysfunctionand apoptosis, vascular expression of adhesion molecules, andrecruitment of inflammatory cells, which then migrate in theintima, thus setting the stage for plaque formation.¹ Coronaryatherosclerotic plaques have a high prevalence in the population,even in subjects dying of non-cardiac causes, and their burdenincreases with age.² In many subjects these plaques remain silentfor life; in others they suddenly become thrombogenic, triggeringocclusive or subocclusive thrombosis, responsible for acutecoronary syndromes. In survivors of a first acute coronary event,the latter is followed by a period, lasting about     

BNP in acute coronary syndromes: the heart expresses its suffering.

The use of N-BNP is well established in the diagnosis and stagingof patients with heart failure¹ and its ability to predict prognosisin this population has been verified in several frequently citedstudies.² Recently, measurement of N-BNP has also been shownto be a useful prognostic tool in the population of patientswith ACS.³ In a past issue of this journal, Bazzino et al.,further extended our knowledge in that they demonstrated theprognostic value of elevated levels of N-terminal B-type natriureticpeptide (N-BNP) in addition to standardised risk-stratificationschemes in patients that were included consecutively with acute coronary syndromes (ACS).⁴ Risk stratification of patients with ACS Although, early treatment with fibrinolytic agents or percutaneouscoronary intervention is well documented in acute ST-elevationmyocardial infarction (STEMI), the optimal treatment strategyfor     

Acute effect of oestrogen replacement therapy on treadmill performance in postmenopausal women with coronary artery disease

The significant reduction in cardiovascular morbidity and mortalityfollowing oestrogen replacement therapy in postmenopausal womenis only partly explained by an improved lipid profile. Givenacutely, oestradiol causes vasodilatation and increases coronaryblood flow and, in large doses, improves treadmill performancein postmenopausal women with coronary artery disease. However,the significance of oestrogen-mediated vasodilatation is unknownsince the acute effects of oestradiol in doses and preparationscommonly used clinically have not been tested. The aim of thisstudy was to evaluate the acute effects of conventional replacementtherapy with 17 ß-oestradiol on treadmill performancein 16 postmenopausal women with angina in a randomized, double-blind,placebo-controlled cross-over trial. Following baseline treadmill testing a transdermal oestrogenpatch releasing 50 µg oestradiol. 24 h^–1 or matchingplacebo was applied and the exercise test repeated 24 h later.The patch was then removed. Seven to 14 days later the sequencewas repeated using the alternative patch. The changes in timeto angina, time to 1 mm ST segment depression and total exercisetime for each treatment compared with the corresponding baselinetest were calculated. Plasma 17 ß-oestradiol increased with active therapyfrom 56±30pmol. l^–1 to 204±90pmol. l^–1,indicating adequate replacement. Compared with their respectivebaseline exercise tests there were no differences between activeand placebo patches for time to angina (active: 13±55s vs placebo: 10±47 s), time to 1 mm ST segment depression(active: –30 ±52 s vs placebo: 24±71 s)or total exercise time (active: 14±45 s vs placebo: 13±35s). Despite the recognized acute vasodilator action of larger dosesof oestrogen, doses conventionally used in hormone replacementtherapy had no acute effect on treadmill performance in thisgroup of postmenopausal women with coronary artery disease.     

Ruminating on OAT: is the case closed?

Occlusion of an epicardial coronary artery is a well recognizedpathophysiological substrate for acute ST-elevation myocardialinfarction (MI). Whether and how coronary patency is restoredafter this event is markedly variable among patients. Unquestionably,coronary reperfusion enhances clinical outcomes and can occurspontaneously or through pharmacological or mechanical methods.¹Moreover, if the culprit coronary artery associated with MIis open prior to an attempt at mechanical coronary intervention,a better long-term clinical outcome results.² Since the long-term outlook for patients recovering from MIappears enhanced when the culprit coronary artery is patent,enthusiasm for     

Long distance transport for primary angioplasty vs immediate thrombolysis in acute myocardial infarction (PRAGUE-2 trial)

To the Editor We read with interest the results of the PRAGUE-2 trial¹andits editorial.²Widimsky et al. compared the effects of transportfor primary percutaneous coronary angioplasty (PCI) and immediatethrombolysis (TL) for patients with acute myocardial infarction(AMI), in the randomized trial PRAGUE-2.¹The authors concludedthat long     

Family history of coronary artery disease -- need to focus on proper definition!

In a large, prospective study, Andresdottir et al.¹reportedthat 15% of coronary events were attributable to family historyof coronary artery disease, when they used history of myocardialinfarction at any age (not premature coronary artery disease)in first-degree relatives.     

Unrecognized heart failure in elderly patients with stable chronic obstructive pulmonary disease

The documentation of a 20.5% prevalence of heart failure (withischaemic heart disease as the underlying cause in 20.2%) instable chronic COPD¹ is consistent with the observation madeby Keistinen et al.² that coronary heart disease was     

Assessment of coronary reserve by transoesophageal Doppler echocardiography: Direct comparison between different modalities of dipyridamole and adenosine administration

BACKGROUND: This study was undertaken to compare the coronary vasodilatorresponse to different application modalities of intravenousvasodilators, in order to identify the optimal pharmacologicalprotocol for the evaluation of coronary reserve by means oftransoesophageal Doppler echocardiography. METHODS: Blood flow velocity in the left anterior descending artery,coronary vascular resistance and left main coronary artery cross-sectionalarea were assessed by transoesophageal echo-Doppler during ani.v. adenosine bolus (5 mg), a 5-min adenosine infusion (infusionrate 140µg.kg^–1.min^–1), and low (0·56mg.kg^–1.min^–1),and high-dose (0·84mg.kg^–1.9min^–1) dipyridamoleinfusions in 10 healthy normals (Group 1) and in 20 patients(Group 2) with either coronary microvascular disease (11 patients)or coronary artery disease (nine patients). RESULTS: In both groups, the highest flow velocity and the lowest coronaryvascular resistance were observed during the adenosine infusion.Flow velocity values and indices of coronary vasodilator capacityobserved after the adenosine bolus and the high-dose dipyridamoleinfusion were very close to those obtained during the adenosineinfusion, especially in Group 1. Coronary flow velocity waslower and coronary vascular resistance higher after low-dosedipyridamole, significantly in Group 2. The maximal flow responseto the adenosine bolus was observed within a few seconds afterthe injection, and was very short. The peak response to theadenosine infusion was observed 57±27 s after its start.The coronary flow velocity response to dipyridamole was dosedependent and differed between Groups 1 and 2. CONCLUSION: In combination with transoesophageal Doppler echocardiography,a short-lasting adenosine infusion at a rate of 140µg.kg^–1.min^–1seems to be preferable to an adenosine bolus and dipyridamoleinfusion. The effect of the bolus is too short for an accuratemeasurement of coronary flow velocity, while the dipyridamoleinfusion, especially at a low dose, induces a submaximal vasodilatorresponse.     

Myocardial Thallium201imaging in hypertrophic obstructive cardiomyopathy

Thallium ²⁰¹ Myocardial perfusion imaging was performed at restand during exercise in 14 patients with hypertrophic obstructivecardiomyopathy without coronary artery disease. The regionalmyocardial Thallium²⁰¹-uptake and distribution ratio of thesepatients were analysed by a semiquantitalive computerized methodand compared with those of six normal subjects. Four of the14 patients had no Thallium²⁰¹ imaging defect. Out of a totalof260 analysed regions of interest in the remaining patients,five regions with reversible and 25 with irreversible Thallium²⁰¹defects could be demonstrated. Most of these defects were localizedin the interventricular septum. The Thallium²⁰¹ defects werenot related to the age of the patients and there was no relationshipbetween the occurrence of reversible Thallium²⁰¹ defects anda pathological myocardial lactate extraction rate during maximalatrial pacing. In patients with left ventricular outflow obstructionat rest (n= 10) the percentage of irreversible defect regionsin the Thallium²⁰¹-scintigram (8.5%) was more than twice ashigh as in those patients with a provocable pressure gradient(3.9%). These data suggest that hypertrophic obstructive cardiomyopathyis often associated with regional ischemia or fibrosis despitenormal coronary arteries. Therefore, in these patients, Thallium201scintigraphy can not be used as a non-invasive screening methodto exclude or prove coronary artery disease     

Coronary plaque composition of culprit/target lesions according to the clinical presentation: a virtual histology intravascular ultrasound analysis

With great interest I read the article by Surmely et al.¹ comparingplaque composition of patients with acute coronary syndrome(ACS) and stable angina     

Women, 'non-specific' chest pain, and normal or near-normal coronary angiograms are not synonymous with favourable outcome.

One of the more troubling findings from gender-based studiesis the observation that only half of women who have chest painsuggesting ischaemia present stenotic coronary lesions (>50%lumen diameter narrowing), whereas the remainder show non-obstructiveor apparently normal arteries at angiography.¹ Women with chestpain and non-obstructive coronary artery disease (CAD) constitutea great source of consternation to practicing physicians. Amongthese patients, there are an unknown number who can be shownto be suffering from cardiac pain presumed to be ischaemic.Most of these women complain of chest pain and disability foryears, and the morbidity is considerable.¹ New findings demonstratethat some of these patients may be at an increased risk of myocardialinfarction and cardiac death.¹ Advanced coronary atheroma canbe present despite a normal or near-normal coronary lumen,²and may provide a link between seemingly normal     

Elevation of CK-MB following percutaneous coronary intervention

We read with great interest the meta-analysis by Roe and colleagues¹on the prognostic significance of creatinine kinase MB isoenzyme(CK-MB) elevations following percutaneous coronary interventions(PCI) in patients with acute coronary syndromes. We do