Device-detected atrial fibrillation and risk for stroke: an analysis of >10,000 patients from the SOS AF project (Stroke preventiOn Strategies based on Atrial Fibrillation information from implanted devices).

OBJECTIVE: The aim of this study was to assess the association between maximum daily atrial fibrillation (AF) burden and risk of ischaemic stroke. BACKGROUND: Cardiac implanted electronic devices (CIEDs) enhance detection of AF, providing a comprehensive measure of AF burden. DESIGN, SETTING, AND PATIENTS: A pooled analysis of individual patient data from five prospective studies was performed. Patients without permanent AF, previously implanted with CIEDs, were included if they had at least 3 months of follow-up. A total of 10 016 patients (median age 70 years) met these criteria. The risk of ischaemic stroke associated with pre-specified cut-off points of AF burden (5 min, 1, 6, 12, and 23 h, respectively) was assessed. RESULTS: During a median follow-up of 24 months, 43% of 10 016 patients experienced at least 1 day with at least 5 min of AF burden and for them the median time to the maximum AF burden was 6 months (inter-quartile range: 1.3-14). A Cox regression analysis adjusted for the CHADS2 score and anticoagulants at baseline demonstrated that AF burden was an independent predictor of ischaemic stroke. Among the thresholds of AF burden that we evaluated, 1 h was associated with the highest hazard ratio (HR) for ischaemic stroke, i.e. 2.11 (95% CI: 1.22-3.64, P = 0.008). CONCLUSIONS: Device-detected AF burden is associated with an increased risk of ischaemic stroke in a relatively unselected population of CIEDs patients. This finding may add to the basis for timely and clinically appropriate decision-making on anticoagulation treatment.

A randomized open-label trial with a crossover comparison of sexual self-confidence and other treatment outcomes following tadalafil once a day vs. tadalafil or sildenafil on-demand in men with erectile dysfunction.

AIM: To compare Sexual Self-Confidence and other treatment outcomes following 8 weeks of treatment with tadalafil 5 mg once a day (OaD) vs. tadalafil 20 mg or sildenafil 100 mg as needed (pro re nata [PRN]) in patients with erectile dysfunction (ED). METHODS: A randomized, open-label, crossover study in men ≥18 years of age with history of ED and satisfactory response to current oral phosphodiesterase 5 (PDE5) inhibitor PRN. Data were analyzed with a mixed effects model for crossover design. MAIN OUTCOME MEASURES: The primary outcome measure was the Sexual Self-Confidence domain of the Psychological and Interpersonal Relationship Scales (PAIRS) between tadalafil OaD and sildenafil PRN. SECONDARY OUTCOMES INCLUDED: Time Concerns and Spontaneity domains of PAIRS, and the Self-Esteem and Relationship (SEAR) scale. RESULTS: Men naive to tadalafil OaD were enrolled (N = 378), with 61-69% prior PDE5 inhibitor use. There were improvements in all PAIRS domains from baseline when comparing tadalafil OaD and PRN with sildenafil PRN (P < 0.001). The Sexual Self-Confidence domain improved from baseline and was 0.50 ± 0.78 following tadalafil OaD, 0.5 ± 0.72 for tadalafil PRN, and 0.39 ± 0.67 for sildenafil PRN. The difference in least-squares mean was 0.12 ± 0.04 (confidence interval [CI] = 0.04, 0.19; P = 0.001) between tadalafil OaD and sildenafil PRN and 0.01 ± 0.04 (CI = -0.06, 0.08; P = 0.872) between tadalafil OaD and tadalafil PRN. The Time Concerns domain score was lower with tadalafil OaD than tadalafil PRN (P < 0.001). There were no differences in SEAR scores between treatments. CONCLUSIONS: Tadalafil OaD and tadalafil PRN compared with sildenafil PRN demonstrated greater improvements in Sexual Self-Confidence, Time Concerns, and Spontaneity. There was no significant difference in Sexual Self-Confidence between tadalafil OaD and tadalafil PRN. Changes in SEAR, the erectile function domain of the International Index of Erectile Function, and the Erectile Dysfunction Inventory of Treatment Satisfaction scores from baseline to end point were similar.

Timing of dose relative to sexual intercourse attempt in previous sildenafil citrate users treated with tadalafil: a geographical comparison from a single arm, open-label study.

INTRODUCTION: Previous research has demonstrated that sildenafil citrate users alter dosing-sexual attempt behavior when switched to tadalafil. The impact of geography and culture on sexual behavior with phosphodiesterase type 5 (PDE5) inhibitor treatment has not been fully investigated. AIM: To describe and compare the changes in dosing-sexual attempt behavior with sildenafil citrate vs. tadalafil treatment across four distinct geographies: Asia, Australia/New Zealand (ANZ), Central Eastern Europe/Middle East (CEE/ME), and Latin America (LA). METHODS: Data from a single-arm, open-label clinical trial conducted in 21 countries from November 2002 to May 2004 were used in this analysis. Men with erectile dysfunction and a history of > or =6-week prior sildenafil citrate use continued sildenafil citrate treatment for 4 weeks then switched to tadalafil for 8 weeks. Dosing instructions were provided. MAIN OUTCOMES MEASURES: Timing of dose and sexual intercourse was assessed through patient diaries for the final 4 weeks of each treatment period. RESULTS: A total of 2,760 men were enrolled: Asia 15.8%; ANZ 29.4%; CEE/ME 19.7%; LA 35.1%. The median time from dosing to intercourse was significantly increased during tadalafil treatment across all geographical regions; however, the magnitude of increase differed significantly by geography (P < 0.0001). The Asian cohort demonstrated the shortest duration between dosing and sexual intercourse attempts (irrespective of drug), and altered sexual behavior the least upon switching to tadalafil. The ANZ cohort demonstrated the longest duration between dosing and sexual intercourse attempts (irrespective of drug), and altered sexual behavior the most upon switching to tadalafil. CONCLUSION: Men with a history of established sildenafil citrate use alter their dose-attempt behavior when treated with tadalafil irrespective of geography. However, the extent to which sexual behavior alters is not uniform across geographical regions, suggesting that dosing instructions and duration of drug effectiveness, in combination with personal and cultural preferences, may determine sexual behavior with PDE5 inhibitor use.

Long-term antipsychotic monotherapy for schizophrenia: disease burden and comparative outcomes for patients treated with olanzapine, quetiapine, risperidone, or haloperidol monotherapy in a pan-continental observational study.

OBJECTIVE: Noninterventional, naturalistic studies facilitate examination of current clinical practices and provide an understanding of the impact of the biopsychosocial aspects of schizophrenia. This article describes disease burden and patient outcomes, with an emphasis on the comparative effectiveness and tolerability of antipsychotic monotherapy. METHOD: Outpatients initiating or changing antipsychotic therapy for DSM-IV- or ICD-10-defined schizophrenia (N = 7658) were allocated to olanzapine or nonolanzapine cohorts (November 2000 to December 2001). Treatment was at the psychiatrist's discretion, including flexible dosing and use of concomitant therapies and medications, with assessments at 0, 3, 6, 12, 18, 24, 30, and 36 months. Longitudinal clinical, pharmacologic, functional, and social data were collected over 36 months across 27 countries. RESULTS: At entry, 76% of patients were initiated/switched to antipsychotic monotherapy, most commonly with olanzapine (N = 3222), risperidone (N = 1117), quetiapine (N = 189), or haloperidol (N = 257). Patients prescribed olanzapine were more likely to maintain their baseline monotherapy (p < .001) and did so for a longer period (p < .001) compared with other antipsychotics. Median time to discontinuation (in months) was as follows: olanzapine 30.0, risperidone 23.1, quetiapine 13.9, haloperidol 12.5. Olanzapine-treated patients were also more likely to respond, and did so more rapidly than patients on other monotherapies (p < .001). Response data were also favorable for risperidone; median time to response (in months) was as follows: olanzapine 5.2, risperidone 6.3, quetiapine 11.3, haloperidol 11.7. Treatment-emergent adverse events varied: olanzapine patients had less favorable odds for significant weight gain (p < .001); haloperidol patients, for motor dysfunction (p < or = .002). CONCLUSION: These naturalistic data from less-studied outpatient communities highlight the variability in clinical and functional outcomes associated with long-term antipsychotic treatment.

Gemcitabine administered as a short infusion versus a fixed dose rate in combination with cisplatin for the treatment of patients with advanced non-small cell lung cancer.

Previous studies have indicated that, in combination with cisplatin, fixed dose rate gemcitabine may be more efficacious than standard infusion gemcitabine. This open-label, randomised phase II study was aimed to compare the efficacy and safety of these regimens as treatment for advanced non-small cell lung cancer (NSCLC) in Latin American patients. Sixty-four patients were randomised to receive up to six cycles of treatment with cisplatin 75 mg/m(2) on Day 1 plus either gemcitabine 1000 mg/m(2) over 30 min on Days 1 and 8 of a 21-day cycle (standard arm, N=33) or gemcitabine 1000 mg/m(2) at a fixed dose rate of 10 mg/m(2)/min on Days 1 and 8 of a 21-day cycle (FDR arm, N=31). In the standard arm, 9 of 33 (27%) patients responded compared with 6 of 30 (20%) patients in the FDR arm (odds ratio: 0.67, 95% CI, 0.21-2.2; p=0.56). Median overall survival was 7.5 months in the standard arm and 9.9 months in the FDR arm. One-year survival rates were 35% and 37% in the standard arm and the FDR arm, respectively. Patients in the FDR arm experienced more grade 3/4 haematological toxicity than those in the standard arm (48% versus 21%). The results of this trial do not support FDR administration of gemcitabine in preference to the standard administration in Latin American patients with NSCLC.

Antiplatelet therapy and progression of coronary artery disease: a placebo-controlled trial with angiographic and clinical follow-up after myocardial infarction.

INTRODUCTION: In patients after ST-elevation myocardial infarction (STEMI), antiplatelet therapy reduces subsequent cardiac events, which are often attributed to recurrent thrombosis with (sub)total occlusion in the infarct-related artery. Whether antiplatelet therapy influences the often subclinical process of coronary disease progression in noninfarct arteries has not been reported. METHODS: Quantitative coronary angiography of noninfarct arteries was performed on paired cine-angiograms of 149 patients from fibrinolytic trials who had a patent infarct-related artery 3 to 4 weeks following STEMI and who were randomized to either continue the daily combination of 50-mg aspirin and 400-mg dipyridamole or to matching placebo. Follow-up angiography was scheduled at 1 year. RESULTS: On a per-patient basis, the change in minimal luminal diameter (MLD) was 0.00 mm in the aspirin/dipyridamole group (n = 76) and was 0.01 mm in the placebo group (n = 73). There was no difference between these groups in the changes in MLD (-0.02 mm; 95% CI -0.09 to 0.05), neither were there significant differences in mean luminal diameter and diameter stenosis. Progression (1 segment/patient with > or = 0.40 mm decrease in MLD) was seen in two thirds of patients and did not independently predict long-term death and/or reinfarction. CONCLUSION: In this placebo-controlled trial after STEMI, the combination of aspirin and dipyridamole did not affect noninfarct artery disease progression. Progression did not predict long-term clinical outcome.

Extra-aortic balloon counterpulsation: an intraoperative feasibility study.

BACKGROUND: Current methods of counterpulsation or ventricular assistance have significant vascular and limb complications. The aim of this study was to determine the safety and performance of a new method of non-blood-contacting counterpulsation using an inflatable cuff around the ascending aorta (extra-aortic balloon [EAB]). METHODS AND RESULTS: In 6 patients undergoing first time off-pump coronary bypass surgery via sternotomy, the EAB was secured around the ascending aorta and attached to a standard counterpulsation console. At baseline and with 1:2 and 1:1 augmentation, hemodynamic and echocardiographic parameters of ventricular function and coronary flow were measured. High-intensity transient signals were measured using transcutaneous Doppler over the right common carotid artery. No complications occurred. With EAB there was no significant change in heart rate or blood pressure and no increase in high-intensity transient signals. There was a 67% increase in diastolic coronary blood flow (mean left-main diastolic velocity time integral 15.3 cm unassisted versus 25.1 cm assisted, P<0.05). Measurements with transesophageal echocardiography at baseline and with 1:1 counterpulsation demonstrated a 6% reduction in end-diastolic area (P=NS), a 16% reduction in end-systolic area (P<0.01), a 31% reduction in left ventricular wall stress (P<0.05), and a 13% improvement in fractional area change (P<0.005). CONCLUSIONS: EAB counterpulsation augments coronary flow and reduces left ventricular afterload. Further testing is warranted to assess the use of the EAB for chronic non-blood-contacting support of the failing heart.

Usefulness of serial measurement of N-terminal pro-brain natriuretic peptide plasma levels in asymptomatic patients with aortic stenosis to predict symptomatic deterioration.

In 29 initially asymptomatic patients with aortic stenosis followed for an average of 18 months, patients with a N-terminal pro-brain natriuretic peptide (NT-pro-BNP) level above the normal range at baseline were more likely to develop symptoms during follow-up compared with patients with NT-pro-BNP within normal limits. The average increase in NT-pro-BNP per year was greater for patients who developed symptoms compared with patients who remained asymptomatic. Aortic valve area, peak aortic velocity, and the ejection fraction were less reliable predictors of symptom onset. Measurement of NT-pro-BNP in addition to clinical assessment and echocardiography may allow more reliable follow-up and timing of valve replacement for aortic stenosis.

Changing donor and recipient demographics in a heart transplantation program: influence on early outcome.

BACKGROUND: The purpose of this study was to investigate whether broadening acceptance criteria for donor hearts and changing recipient demographics resulted in an increased perioperative morbidity and mortality in a heart transplant program. METHODS: Donor and recipient data of 137 consecutive heart transplants performed from 1987 to 2001 were retrospectively analyzed and divided into three equal eras, each of 5 years: 1987 to 1991, 1992 to 1996, and 1997 to 2001. Multivariate analyses of recipient and donor demographics and operative factors were performed to identify the predictors of low cardiac output, intraaortic balloon pump utilization, 30-day mortality, and duration of intensive care and hospital stay. RESULTS: Significant increases in number of female recipients (p = 0.025), cardiopulmonary bypass (p < 0.001), recipient cross-clamp (p < 0.001), donor age (p = 0.009), donor ischemic times (p < 0.001), use of cardioplegia (p < 0.001) and the bicaval technique (p < 0.001), brain death to retrieval time (p = 0.006), and need for postoperative dialysis were observed for the three study periods, whereas length of intensive care and hospital stay decreased. Female donor (odds ratio [OR], 2.4; 95% confidence interval [CI], 1.0 to 5.7) was identified as a risk factor for low cardiac output. Female donor (OR, 3.7; 95% CI, 1.3 to 10.7), donor cardiac arrest (OR, 6.4; 95% CI, 1.6 to 25.9), and cardiopulmonary bypass time more than 2 hours (OR, 7.6; 95% CI, 2.1 to 28.1) were associated with increased intraaortic balloon pump utilization. Intensive care stay was prolonged by the biatrial technique (OR, 3.9; 95% CI, 1.3 to 11.9) and reduced by the use of cardioplegia (OR, 0.3; 95% CI, 0.1 to 0.9), longer cardiopulmonary bypass (OR, 0.2; 95% CI, 0.1 to 0.6) and aortic cross-clamp times (OR, 0.1; 95% CI, 0.03 to 0.6). CONCLUSIONS: Although a number of significant changes were observed during the study period, no donor, recipient, or operative factors influenced 30-day mortality. This study justifies our current donor and recipient selection policies.

Use of Monogen for pediatric postoperative chylothorax.

BACKGROUND: Postoperative chylothorax is a potentially serious complication of pediatric cardiac surgery. The purpose of this study was to report the use of Monogen enteral formula for the management of pediatric postoperative chylothorax. METHODS: A retrospective, single-institution 2-year study of all patients with a diagnosis of postoperative chylothorax was conducted. Chylothorax was diagnosed in 25 patients after a total of 535 cardiac operations in children younger than 10 years, for an incidence of 4.7%. Eighteen patients had been given Monogen, an enteral low long-chain triglyceride formula, as initial treatment. Six had been given total parenteral nutrition. The following variables were related to outcome and response to Monogen: age, sex, weight, underlying condition, type of surgery, interval between surgery and chylothorax diagnosis, duration and daily volume of chyle leak, central venous pressure, residual lesions, and weight loss. RESULTS: Enteral feeding with Monogen was successful for 14 of 18 patients with a response to treatment evident by the end of the third day. No variables predicted which patients would respond to Monogen. Body weight was maintained or increased in 14 of the 17 surviving patients taking Monogen. A return to normal diet at 4 +/- 1 weeks from the day of pleural drain removal did not result in recurrent chylothorax. CONCLUSIONS: A trial of Monogen is recommended as initial treatment for postoperative chylothorax unless enteral feeding is contraindicated.

Depression and cardiovascular morbidity and mortality: cause or consequence?

BACKGROUND: Depression after myocardial infarction has been associated with increased cardiovascular mortality. This study assessed whether depressive symptoms were associated with adverse outcomes in people with a history of an acute coronary syndrome, and evaluated possible explanations for such an association. METHODS AND RESULTS: Depressive symptoms were assessed using the General Health Questionnaire at least 5 months after hospital admission for acute myocardial infarction or unstable angina in 1130 participants of the Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study, a multicentre, placebo-controlled, clinical trial of cholesterol-lowering treatment. Cardiovascular symptoms, self-rated general health, cardiovascular risk factors, employment status, social support and life events were also assessed at the baseline visit. Cardiovascular death (n=114), non-fatal myocardial infarction (n=108), non-fatal stroke (n=53) and unstable angina (n=274) were documented during a median follow-up period of 8.1 years. Individuals with depressive symptoms (General Health Questionnaire score >/=5; 22% of participants) were more likely to report angina, dyspnoea, claudication, poorer general health, not being in paid employment, few social contacts and/or adverse life events (P<0.05 for all). There was a modest association between depressive symptoms and cardiovascular events (hazard ratio [HR] 1.42, 95% confidence interval [CI] 1.13-1.77), but not cardiovascular death (HR 1.12. 95% CI 0.71-1.77). After adjustment for symptoms related to cardiovascular disease, the HR for cardiovascular events was 1.22 (95% CI 0.97-1.53). After further adjustment for employment status, social support and life events, the HR was 1.13 (95% confidence interval 0.87-1.47). CONCLUSIONS: There was no significant association between depressive symptoms and fatal or non-fatal cardiovascular events after adjustment for cardiovascular symptoms associated with poorer prognosis. Previously observed associations between depression and cardiovascular mortality may not be causal.

Effect of aortic valve replacement on c-reactive protein in nonrheumatic aortic stenosis.

Plasma levels of C-reactive protein were higher in 20 patients with bicuspid or trileaflet degenerative aortic stenosis than in 31 normal controls and in 19 patients with pure aortic regurgitation. C-reactive protein decreased from before to 6 months after aortic valve replacement for aortic stenosis. These observations suggest that aortic stenosis is an inflammatory disease.

Associations between plasma natriuretic peptide levels, symptoms, and left ventricular function in patients with chronic aortic regurgitation.

In 40 patients with chronic moderate to severe aortic regurgitation, brain natriuretic peptide, N-brain natriuretic peptide, and atrial natriuretic peptide were higher in symptomatic patients compared with asymptomatic patients after adjustment for age, gender, and ejection fraction, but each natriuretic peptide correlated weakly with echocardiographic measures of left ventricular size and function. In patients with chronic aortic regurgitation, measurement of natriuretic peptide levels may provide information on left ventricular function in addition to echocardiography.

Plasma natriuretic peptide levels increase with symptoms and severity of mitral regurgitation.

OBJECTIVES: This paper will describe associations between plasma natriuretic peptide levels and the severity and symptoms of mitral regurgitation (MR). BACKGROUND: A biochemical test that assisted grading of the severity of MR and the interpretation of symptoms would be of clinical value. METHODS: Forty-nine patients with isolated MR and left ventricular (LV) ejection fractions (EFs) of >55% underwent transthoracic echocardiography, assessment of symptoms, and measurement of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and its amino-terminal portion, N-BNP. RESULTS: The level of each natriuretic peptide rose with increasing severity of MR and with increases in left atrial (LA) dimensions (p < 0.001 for all comparisons), but no significant correlation existed between any natriuretic peptide and the LV dimensions or EF. Natriuretic peptide levels were higher in symptomatic MR (n = 16, BNP geometric mean 16.9 [95% confidence interval (CI) 13.3 to 21.4] pmol/l) compared with asymptomatic MR (n = 33, BNP 7.1 [95% CI 6.0 to 8.4] pmol/l, p < 0.001), and higher in asymptomatic MR than in normal controls (n = 100, BNP 5.3 [95% CI 4.8 to 5.8] pmol/l, p < 0.0001). These differences were similar for N-BNP and ANP and remained statistically significant (p < 0.05) after adjustment for echocardiographic measures of LV function and severity of MR. Both the sensitivity and the specificity for symptoms for the natriuretic peptides (area under receiver-operator characteristic curve for BNP = 0.90, N-BNP = 0.89, ANP = 0.89) were similar to the MR score (0.88) and greater than for LA dimension (0.81), vena contracta width (0.82), and LV end-systolic dimension (0.63). CONCLUSIONS: Plasma natriuretic peptides levels increase with the severity of MR and are higher in symptomatic compared to asymptomatic patients, even when LV EF is normal.

Increased plasma natriuretic peptide levels reflect symptom onset in aortic stenosis.

BACKGROUND: The onset of symptoms is a critical point in the natural history of aortic stenosis and the cardinal indication for valve replacement. This study assessed the associations between natriuretic peptide levels, disease severity, and cardiac symptoms in aortic stenosis. METHODS AND RESULTS: Seventy-four patients with isolated aortic stenosis underwent independent assessment of symptoms, transthoracic echocardiography, and measurement of plasma levels of atrial natriuretic peptide, brain natriuretic peptide (BNP), and N-BNP. Natriuretic peptide levels were also measured in 100 clinically normal control subjects. The aortic valve area was smaller in symptomatic patients (n=45) than in asymptomatic patients (n=29; mean, 0.71+/-0.23 cm2 and 0.99+/-0.31 cm2, respectively; P<0.0001). Plasma natriuretic peptide levels were higher in symptomatic patients than in asymptomatic patients (for N-BNP: median, 112 versus 33 pmol/L; interquartile range, 70 to 193 versus 16 to 58 pmol/L, respectively; P=0.0002). After adjustment for age, sex, serum creatinine, aortic valve area, and left ventricular ejection fraction, N-BNP levels were 1.74 times higher (95% confidence interval, 1.12 to 2.69) for symptomatic than asymptomatic patients with aortic stenosis (P=0.014). Natriuretic peptide levels increased with the New York Heart Association class (for N-BNP median values were 13, 34, 105, and 202 pmol/L for normal control subjects, class I, class II, and class III/IV patients, respectively; interquartile ranges for the same patients were 8 to 21, 16 to 58, 57 to 159, and 87 to 394 pmol/L; P<0.0001). Similar associations were observed for BNP and atrial natriuretic peptide. CONCLUSIONS: Plasma natriuretic peptide levels are elevated in symptomatic patients with aortic stenosis. Measurement of natriuretic peptides may complement clinical and echocardiographic evaluation of patients with aortic stenosis.

Extended follow up after isolated aortic valve replacement in the elderly.

The present paper reviews the extended follow up of all patients aged >/=70 who underwent isolated aortic valve replacement at our institution in the 1980s. Patients were identified from the surgical database and clinical information was gathered. Long-term follow up information was obtained from the patient, their family, or doctor. Ninety-three patients aged >/=70 years (median 73, range 70-80) comprised the study population. The indication for surgery was aortic stenosis in 68 patients (73%). Fifty-two patients (56%) received an allograft valve, 17 (18%) a bioprosthetic valve, and 24 (26%) a mechanical prosthesis. The median hospital stay was 12 days (range 0-105 days). Five surgical deaths occurred. Detailed follow up was obtained for the 71 patients who died later, and the 16 living patients (one patient lost). The median length of follow up was 6.8 years (range 0.1-18.9 years). Patients who received an allograft aortic valve had a significantly better long-term survival (median 10.6, 95% confidence intervals (CI) 8.1-13.8 years) compared to those receiving mechanical or bioprosthetic valves (median 6.5, 95% CI 4.7-11.9 years), P = 0.03. For the entire group, survival was similar to the age- and sex-matched population. Of the 16 patients alive at follow up (mean age 87, range 83-92), most were free of angina (12, 75%) and heart failure (10, 63%). The conclusion from the current study is that isolated aortic valve surgery in the elderly, particularly with an allograft valve, is associated with an excellent long-term outcome. A survival benefit was demonstrated comparing allograft aortic valve replacement to other valve types.

Increased myocardial ischemia after food is not explained by endothelial dysfunction.

BACKGROUND: Recent studies suggest that a high-fat meal can impair endothelial function. The aim of this study was to determine whether greater myocardial ischemia after either a low-fat or a high-fat meal is associated with an increase in brachial artery endothelial dysfunction. METHODS: Twenty subjects with coronary artery disease and > or =1-mm ST-segment depression during exercise were studied. In a randomized, double-blind, crossover design, ST-segment changes during treadmill exercise and brachial artery diameter and flow-mediated dilation were measured before and 3 hours after a low-fat milkshake meal or the same meal supplemented with 64 grams of cooked fat. RESULTS: After the low-fat but not the high-fat meal, resting brachial artery diameter decreased (before meal 4.72 +/-0.50 mm, after low fat meal 4.62 +/-0.49 mm, P =.001; after high fat meal 4.70 +/-0.51 mm, not significant). High-flow brachial artery diameter was similar before (4.81 +/- 0.48 mm) and after the low-fat (4.82 +/- 0.48 mm) and high-fat (4.84 +/- 0.48 mm) meals (P >.05 for all). Brachial artery flow-mediated dilation was not impaired after either meal. Exercise duration decreased more after the low-fat meal (mean change 39 seconds, 95% CI -14 to -63 seconds, P =.004) than after the high-fat meal (-7 seconds, 95% CI +19 to -34 seconds, not significant). ST-segment depression during equivalent exercise was greater after compared with before both meals (before meals 1.03 +/- 0.69 mm, after low fat 1.27 +/- 0.80 mm, P =.03; after high fat 1.24 +/- 0.74 mm, P =.04). CONCLUSIONS: Increased myocardial ischemia after food is caused by mechanisms other than endothelial dysfunction and by meal components other than cooked fat.