Randomised Controlled Trial: Partial Hydrolysation of Casein Protein in Milk Decreases Gastrointestinal Symptoms in Subjects with Functional Gastrointestinal Disorders.

Unspecific gastrointestinal symptoms associated with milk consumption are common. In addition to lactose, also other components of milk may be involved. We studied whether the partial hydrolysation of milk proteins would affect gastrointestinal symptoms in subjects with functional gastrointestinal disorders. In a randomised, placebo-controlled crossover intervention, subjects (n = 41) were given ordinary or hydrolysed high-protein, lactose-free milkshakes (500 mL, 50 g protein) to be consumed daily for ten days. After a washout period of ten days, the other product was consumed for another ten days. Gastrointestinal symptoms were recorded daily during the study periods, and a validated irritable bowel syndrome-symptom severity scale (IBS-SSS) questionnaire was completed at the beginning of the study and at the end of both study periods. Blood and urine samples were analysed for markers of inflammation, intestinal permeability and immune activation. Both the IBS-SSS score (p = 0.001) and total symptom score reported daily (p = 0.002) were significantly reduced when participants consumed the hydrolysed product. Less bloating was reported during both study periods when compared with the baseline (p < 0.01 for both groups). Flatulence (p = 0.01) and heartburn (p = 0.03) decreased when consuming the hydrolysed product but not when drinking the control product. No significant differences in the levels of inflammatory markers (tumor necrosis factor alpha, TNF-α and interleukin 6, IL-6), intestinal permeability (fatty acid binding protein 2, FABP2) or immune activation (1-methylhistamine) were detected between the treatment periods. The results suggest that the partial hydrolysation of milk proteins (mainly casein) reduces subjective symptoms to some extent in subjects with functional gastrointestinal disorders. The mechanism remains to be resolved.

Pericardial fluid: assessment and examination.

Pericardial fluid is a common finding on echocardiography. Less than 10 mm of fluid on ultrasound scan is not necessarily associated with any significant illness. Clinical examination, blood count, renal and liver enzymes and thyroid function tests as well as inflammatory marker tests are often adequate for a patient who is in good health. A significant amount of fluid requires further investigations, especially in a symptomatic patient. Cancers, infections and various systemic diseases are the most common causes of prominent effusion.

[Cardiac effects of radiation therapy]. / Sädehoidon sydänvaikutukset.

Because of increased life-expentancy cancer patients having undergone radiation therapy nowadays live longer, and late-appearing adverse effects are therefore playing a more significant role. Radiation therapy given to the chest is known to approximately double the risk of heart disease, the cumulative total radiation dose being the most important risk-increasing factor. The most significant adverse effects appear only years after the treatment. The mortality from late manifestations reduces the total benefit of radiation therapy. Patients with radiation therapy due to a cancer of the left breast or Hodgkin's lymphoma are particularly susceptible to cardiac effects. A safe radiation dose is not known.

New-onset atrial fibrillation at discharge in patients after coronary artery bypass surgery: short- and long-term morbidity and mortality.

OBJECTIVES: Atrial fibrillation (AF) after coronary artery bypass surgery is often considered a non-harmful and self-terminating condition. We studied the mortality and morbidity in patients with new-onset AF (NOAF) present at the time of hospital discharge. METHODS: We conducted a retrospective follow-up study of 138 patients discharged in NOAF (NOAF group) and a propensity score-matched control group of 138 patients who were in sinus rhythm (SR) at the time of discharge (SR group). Follow-up data were obtained from the hospitals' records, from the national registry of hospital discharge diagnoses and death records from the Finnish Statistical Bureau. RESULTS: At 3 and 12 months after surgery, AF was present in 20.3 and 23.2% of patients in the NOAF group, respectively, but in none of the patients in the SR group (P < 0.001). At the end of follow-up (8.5 ± 2.8 years), 28.3 and 5.1% of the patients who survived in the NOAF and SR groups, respectively, were in chronic AF (P < 0.001). All-cause mortality (33.3 vs 18.8%, P = 0.002) and cardiac mortality (15.2 vs 4.3%, P = 0.001) were higher in the NOAF group when compared with the SR group. The incidence of cerebrovascular disorders in the NOAF and SR groups did not differ from each other (13.8 vs 10.9%, P = NS). Independent risk factors for all-cause death were NOAF [P = 0.024, hazard ratio (HR) 1.828, 95% CI 0.547-3.09], age (P = 0.0025, HR 1.074, 95% CI 1.026-1.13), diabetes (P = 0.015, HR 1.965, 95% CI 1.142-3.38) and prolonged respiratory support (P = 0.00024, HR 3.394, 95% CI 1.767-6.52). In addition, patients in the NOAF group had more hospitalizations due to heart failure (7.2 vs 0.7%, P < 0.001) and had a higher rate of implantation of permanent pacemakers (6.5 vs 0.4%, P < 0.001). CONCLUSIONS: A majority of NOAF patients revert to SR during the first months after surgery. On the other hand, 20-25% of NOAF patients develop chronic AF during long-term follow-up. Almost half of the NOAF patients were hospitalized during follow-up due to cardiovascular causes. Similarly, NOAF was associated with increased mortality due to cardiac causes, but not increased risk of stroke. This highlights the need for proper oral anticoagulation therapy in these patients.

A spread containing bioactive milk peptides Ile-Pro-Pro and Val-Pro-Pro, and plant sterols has antihypertensive and cholesterol-lowering effects.

Lifestyle intervention is recommended as the primary treatment for mild hypertension and hypercholesterolemia. We studied the effects of a spread containing bioactive milk peptides IPP and VPP, as well as plant sterols, on cardiovascular risk factors in 104 hypertensive, hypercholesterolemic subjects in a randomised, placebo-controlled double-blind intervention. Middle-aged subjects consumed 20 g day⁻¹ of a spread containing 4.2 mg of IPP and VPP as well as 2 g of plant sterols for 10 weeks after a 2 week run-in period. Blood pressure was measured at home 3 times a week. Office blood pressure and 24 h ambulatory blood pressure measurements were performed at the end of the run-in and intervention periods. Blood samples were analysed for serum lipids, plasma glucose and inflammation markers. A significant decrease (-4.1 mmHg vs. -0.5 mmHg, p = 0.007) in systolic blood pressure was seen in the active group, compared to placebo at home measurements. Office blood pressure and 24 h nighttime or daytime ambulatory systolic or diastolic pressure did not differ between the groups. Total (-0.16 vs. 0.25 mmol l⁻¹, p = 0.005) and LDL cholesterol (-0.16 vs. 0.18 mmol l⁻¹, p = 0.006) decreased significantly in the active group compared to the placebo. No significant differences between groups were seen for plasma glucose or inflammation markers. The results thus suggest that milk peptides IPP and VPP and plant sterols, in a low-fat spread matrix, produce a clinically significant reduction in systolic blood pressure as well as serum total and LDL cholesterol without adverse effects. Functional foods that affect 2 major risk factors offer a safe and convenient way to reduce the risk of cardiovascular disease by supporting lifestyle intervention.

Levosimendan reduces heart failure after cardiac surgery: a prospective, randomized, placebo-controlled trial.

OBJECTIVE: To investigate whether levosimendan diminishes the incidence of heart failure after cardiac surgery. DESIGN: Prospective, randomized, placebo-controlled clinical study. SETTING: Cardiac surgery operating room and postanesthesia care unit in a university hospital. PATIENTS: Two hundred patients assigned to undergo heart valve or combined heart valve and coronary artery bypass grafting surgery. INTERVENTIONS: Patients were randomized to receive a 24-hr infusion of placebo or levosimendan administered as a 24 µg/kg bolus over 30-mins and thereafter at a dose of 0.2 µg/kg/min. MEASUREMENTS AND MAIN RESULTS: Heart failure was defined as cardiac index<2.0 L/min/m or failure to wean from cardiopulmonary bypass necessitating inotrope administration for at least 2 hrs postoperatively. Heart failure was less frequent in the levosimendan compared to the placebo group: 15 patients (15%) in the levosimendan and 59 patients (58%) in the placebo group experienced heart failure postoperatively (risk ratio 0.26; 95% confidence interval 0.16-0.43; p<.001). Accordingly, a rescue inotrope (adrenaline) was needed less frequently in the levosimendan compared to the placebo group (risk ratio 0.11; 95% confidence interval 0.01-0.89), p=.005. Intra-aortic balloon pump was utilized in one patient (1%) in the levosimendan and in nine patients (9%) in the placebo group (risk ratio 0.11; 95% confidence interval 0.01-0.87), p=.018. The hospital and the 6-month mortality were comparable between groups. There were no significant differences in major organ failures postoperatively. Eighty-three patients were hypotensive and needed noradrenaline in the levosimendan compared to 52 patients in the placebo group, p<.001. The cardiac enzymes (creatine kinase MB isoenzyme mass) indicating myocardial damage were lower in the levosimendan group on the first postoperative day, p=.011. CONCLUSIONS: In the present study, levosimendan infusion reduced the incidence of heart failure in cardiac surgery patients but was associated with arterial hypotension and increased requirement of vasopressor agents postoperatively. Improved mortality or morbidity was not demonstrated.

Metoprolol versus amiodarone in the prevention of atrial fibrillation after cardiac surgery: a randomized trial.

BACKGROUND: Current guidelines recommend ß-blockers as the first-line preventive treatment of atrial fibrillation (AF) after cardiac surgery. Despite this, 19% of physicians report using amiodarone as first-line prophylaxis of postoperative AF. Data directly comparing the efficacy of these agents in preventing postoperative AF are lacking. OBJECTIVE: To determine whether intravenous metoprolol and amiodarone are equally effective in preventing postoperative AF after cardiac surgery. DESIGN: Randomized, prospective, equivalence, open-label, multicenter study. (ClinicalTrials.gov registration number: NCT00784316) SETTING: 3 cardiac care referral centers in Finland. PATIENTS: 316 consecutive patients who were hemodynamically stable and free of mechanical ventilation and AF within 24 hours after cardiac surgery. INTERVENTION: Patients were randomly assigned to receive 48-hour infusion of metoprolol, 1 to 3 mg/h, according to heart rate, or amiodarone, 15 mg/kg of body weight daily, with a maximum daily dose of 1000 mg, starting 15 to 21 hours after cardiac surgery. MEASUREMENTS: The primary end point was the occurrence of the first AF episode or completion of the 48-hour infusion. RESULTS: Atrial fibrillation occurred in 38 of 159 (23.9%) patients in the metoprolol group and 39 of 157 (24.8%) patients in the amiodarone group (P = 0.85). However, the difference (-0.9 percentage point [90% CI, -8.9 to 7.0 percentage points]) does not meet the prespecified equivalence margin of 5 percentage points. The adjusted hazard ratio of the metoprolol group compared with the amiodarone group was 1.09 (95% CI, 0.67 to 1.76). LIMITATIONS: Caregivers were not blinded to treatment allocation, and the trial evaluated only stable patients who were not at particularly elevated risk for AF. The withdrawal of preoperative ß-blocker therapy may have increased the risk for AF in the amiodarone group. CONCLUSION: The occurrence of AF was similar in the metoprolol and amiodarone groups. However, because of the wide range of the CIs, the authors cannot conclude that the 2 treatments were equally effective. PRIMARY FUNDING SOURCE: The Finnish Foundation for Cardiovascular Research and the Kuopio University EVO Foundation.

Health-related quality of life after coronary artery bypass grafting: a review of randomized controlled trials.

Objective outcome measures (i.e., survival, mortality, morbidity, complication rate, symptom recurrence, and need for re-interventions) have long been used as benchmarks for successful cardiac surgery, including coronary artery bypass grafting (CABG). Along with these objectively measurable outcome indicators, acquired improvement by cardiac surgery in subjectively experienced health-related quality of life (HRQoL) has gained importance during the last decade in cardiac surgical research. If an increasing proportion of adult patients referred for CABG are elderly, octogenarians or even nonagenarians, the acquired HRQoL benefit from bypass surgery should be considered to be at least as important an outcome measure as potentially marginal improvement in life expectancy or longevity alone. To achieve the maximal HRQoL benefit and to optimize patient selection, a comprehensive analysis and understanding of contributors that affect pre- and postoperative self-perceived HRQoL is essential. These include patient-related characteristics (e.g., demographics and underlying comorbidities), surgical technique-related factors, and healthcare-related attributes. In this paper we review the randomized controlled trials published during the last ten years to analyze the effect of CABG on HRQoL. Specifically, we focus on the differences between the on-pump and off-pump (OPCAB) bypass techniques, investigate the factors that contribute to post-CABG HRQoL, and study post-CABG HRQoL in elderly patients.

[The treatment of valvular heart disease]. / Läpplivikojen kehittyvä hoito.

During the last few years, progress has been made in the diagnostics and treatment of valvular heart disease. Valvuloplasties have become more common in cases of valve leakage, whereby complications associated with artificial valves and anticoagulant therapy can be avoided. New less invasive catheter valve techniques seem to be as good as conventional ones. In the treatment of aortic valve stenosis, artificial valve replacement via catheter has become almost routine for patients having an excessive risk in open heart surgery.

Cardiac sympathetic activity is associated with inflammation and neurohumoral activation in patients with idiopathic dilated cardiomyopathy.

BACKGROUND: Idiopathic dilated cardiomyopathy (IDC) is characterized by sympathetic nervous overactivity, inflammation and neurohumoral activation; however, their interrelationships are poorly understood. METHODS AND RESULTS: We studied 99 patients with IDC (age 54 +/- 1 years, left ventricular ejection fraction (EF) 40 +/- 1%, maximum oxygen uptake (VO(2)max) 20 +/- 1 ml kg(-1) min(-2), mean +/- SEM) by using (123)I-metaiodobenzylguanidine (MIBG) imaging. MIBG washout and MIBG heart/mediastinum (H/M)-ratio at 4 h postinjection were calculated. In addition, the plasma levels of interleukin (IL)-6 and N-terminal B-type natriuretic peptide (NT-proBNP) were measured. MIBG washout and MIBG H/M ratio had a significant correlation with IL-6 (r = 0.42, P<0.001 and r = -0.31, P<0.01) and NT-proBNP (r = 0.48, P<0.001 and r = -0.40, P<0.001). During a median follow-up of 4.1 years, 20 patients (20%) had an adverse cardiac event (death, heart transplantation or application of biventricular pacemaker or implantable cardioverter-defibrillator). In these patients, MIBG washout was higher (53 +/- 4 versus 40 +/- 2%, P = 0.01) and H/M ratio lower (1.38 +/- 0.04 versus 1.51 +/- 0.02, P = 0.01) than in patients without an event. CONCLUSIONS: In dilated cardiomyopathy, myocardial sympathetic innervation and activity are related to inflammation and neurohumoral activation. These relationships are at least partly independent of left ventricular function and exercise capacity.

Pacemaker therapy after tricuspid valve operations: implications on mortality, morbidity, and quality of life.

BACKGROUND: We studied the incidence and predictors of permanent pacemaker implantation after tricuspid valve operation and its implications on patient outcome in terms of survival, morbidity, and quality of life. METHODS: Between 1992 and 2007, 136 consecutive patients underwent tricuspid valve repair or valve replacement with a biologic valve at Kuopio University Hospital. Comprehensive clinical data were recorded prospectively. Data for the Nottingham Health Profile quality of life analysis were collected cross-sectionally. RESULTS: The mean follow-up time was 7.9 +/- 4.1 years (range, 0.8 to 15.7 years). A pacemaker was implanted in 28 patients (21%); 54% were implanted before hospital discharge. The 10-year survival of patients with a pacemaker was higher (94%) than of patients without a pacemaker (59%; p = 0.050). The need of a pacemaker was related to a significantly higher rate of transient ischemic attacks (30% vs 6%, p = 0.004), strokes (9% vs 4%; p = 0.008), and impaired physical capacity in terms of higher New York Heart Association functional class (p = 0.03) and the quality of life scores describing energy (31 vs 17; p = 0.01) and mobility (32 vs 17; p = 0.005). CONCLUSIONS: The need for pacemaker implantation after tricuspid valve operations was high. Unexpectedly, the life expectancy of the patients who needed a pacemaker postoperatively was higher compared with those who did not. This beneficial effect on mortality was offset by impaired morbidity: patients with a pacemaker experienced a significantly higher rate of thromboembolic complications and impaired quality of life.

Prospective assessment of quality of life of octogenarians after cardiac surgery: factors predicting long-term outcome.

Our objective was to assess the long-term prognosis and quality of life (QoL) of elderly patients after cardiac surgery. The Nottingham Health Profile (NHP) QoL data were recorded from 104 patients who were older than 70 years at the time of primary cardiac surgery in 1993. All living patients were controlled at 15+/-3.2 months and 8.2+/-0.27 years after discharge. The 1-year, 5-year and actual survival rates were 94%, 76%, and 59%, respectively. Risk factors for death were urgency of the operation (relative risk ratio, 2.0; 95% confidence interval, 1.2-3.6), ejection fraction below 50% (2.1; 1.1-3.9), and preoperative renal failure (2.1; 1.0-4.0). Cardiac operated octogenarians took advantage from age and sex matched reference populations at 15 months in the NHP dimension of pain (P=0.001). The QoL decreased gradually during the follow-up similarly in both groups in dimensions describing energy (P=0.001), pain (P=0.003), and mobility (P=0.042). Diabetes, low energy score and high pain score at 15 months, treatment in intensive care unit >3 days, and duration of symptoms >120 days preoperatively were associated with impaired QoL. Survival and QoL were similar for cardiac operated octogenarians and age and sex matched controls at 15 months and 8.2 years after cardiac surgery.

Cytokines, interstitial collagen and ventricular remodelling in dilated cardiomyopathy.

BACKGROUND: Dilated cardiomyopathy (DCM) is associated with myocardial fibrosis, and proinflammatory cytokines may play a role in this. METHODS: N-terminal type I and III procollagen propeptides (PINP, PIIINP) and cross-linked telopeptide of type I collagen (ICTP) were measured from serum samples of 73 patients with DCM and 56 age and sex matched controls. Circulating cytokine levels were determined in DCM patients. RESULTS: Serum levels of PINP and PIIINP were lower in patients than in controls (p<0.05 and p=0.001). In patients with DCM, the levels of PIIINP and ICTP correlated significantly with each other (p<0.01), and the proinflammatory cytokines, tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6), correlated positively with ICTP (p<0.001, p<0.05), PIIINP/PINP ratio (p<0.05, p<0.01) and left atrial size (p<0.01, p<0.05). Presence of atrial fibrillation was associated with lower serum PINP level and higher PIIINP/PINP ratio (p<0.05). CONCLUSIONS: Our results suggest that interstitial myocardial collagen metabolism is altered in DCM patients and regulated by proinflammatory cytokines. These changes in collagen metabolism are associated with presence of atrial fibrillation, but do not reflect left ventricular remodelling. Treatment with beta-blockers and inhibitors of the renin angiotensin aldosterone system seem to effectively inhibit overall type I and III collagen syntheses.

Intravenous administration of metoprolol is more effective than oral administration in the prevention of atrial fibrillation after cardiac surgery.

BACKGROUND: Atrial fibrillation (AF) is the most common arrhythmia to occur after cardiac surgery, with an incidence of 20% to 40%. AF is associated with postoperative complications, including increased risk of stroke and need of additional treatment, as well as prolonged hospital stay and increased costs. It has been shown that prophylactic oral administration of beta-blocker therapy reduces the incidence of postoperative AF after cardiac surgery. However, it is possible that absorption of drugs is impaired after cardiopulmonary perfusion associated with cardiac surgery. The purpose of this prospective, controlled, randomized trial was to study compare intravenous and per oral metoprolol administration in the prevention of AF after cardiac surgery. METHODS AND RESULTS: 240 consecutive patients who were scheduled to undergo their first on-pump coronary artery bypass graft (CABG), aortic valve replacement, or combined aortic valve replacement and CABG were randomized to receive 48-hour infusion of metoprolol or oral metoprolol starting on the first postoperative morning. Patients were excluded if they had contraindications for beta-blocker or had to stay >1 day in the intensive care unit. Dosage of metoprolol was adjusted according to heart rate. The dosage was 1 to 3 mg/h in the intravenous group and from 25 mg twice per day to 50 mg 3 times per day in the oral group. The incidence of postoperative AF was significantly lower in the intravenous group than in the oral group (16.8% versus 28.1%, P=0.036). No serious adverse effects were associated with intravenous metoprolol therapy. CONCLUSIONS: Our study suggests that intravenous metoprolol is well-tolerated and more effective than oral metoprolol in the prevention of AF after cardiac surgery.

Early and late outcome after coronary artery bypass surgery in diabetic patients.

OBJECTIVE: To determine the impact of diabetes on outcome after coronary artery bypass surgery. DESIGN: We matched 866 diabetic patients with non-diabetic controls in regards to gender, age, left ventricular ejection fraction, body mass index, presence of unstable angina and history of myocardial infarction, and day of surgery. The 30-d mortality and morbidity were evaluated with univariate analysis and survival and freedom from cardiac death were assessed with the Kaplan-Meier method. RESULTS: Follow-up time was 69+/-37 months. The 30-d mortality was 2.0% in the diabetic group and 1.0% in the non-diabetic group (p=0.15). Postoperative morbidity did not differ between groups. Cumulative 5- and 10-year survival rates were 89 and 71% in diabetics and 94 and 84% in non-diabetics (p=0.001). During follow-up, there was no difference between groups in regards to repeat revascularization. CONCLUSIONS: The 30-d mortality was equally low in diabetic and non-diabetic patients with severe coronary artery disease. However, long-term survival was significantly lower in the diabetic group than in the non-diabetic group.

Right atrial overdrive pacing does not prevent atrial fibrillation after coronary artery bypass surgery.

AIMS: The purpose of this prospective randomized study was to investigate the efficacy of atrial overdrive pacing (AOP) and bradycardia prevention pacing (BPP) in the prophylaxis of atrial fibrillation (AF) after coronary artery bypass surgery (CABG). METHODS: One hundred and twenty-four on-pump CABG patients were randomized into three groups: AOP, BPP, and NP (no pacing). AOP patients were paced via epicardial wires using an atrial preference pacing algorithm, and BPP patients were paced in the AAI mode with a base rate of 60/min. Patients were paced for 48 h starting on the first postoperative day. The endpoint of the study was the first onset of AF lasting longer than 5 min. RESULTS: Preoperative risk factors and surgical data of patients did not differ between the AOP, BPP and NP groups. Pacing was technically successful in 80.5% of patients in the AOP and in 92.7% in the BPP groups. The incidence of AF in the AOP (26.8%), BPP (19.5%) and NP (28.6%) groups did not differ significantly. In the AOP group, AF in three patients was probably induced by inappropriate pacing due to sensing failure. CONCLUSIONS: Atrial overdrive pacing and bradycardia prevention pacing were not effective in the prevention of AF after CABG.

Inhibition of platelet-collagen interaction: an in vivo action of insulin abolished by insulin resistance in obesity.

Insulin resistance is associated with an increased risk of atherothrombotic vascular disease, but the mechanisms are poorly understood. We determined how insulin in vivo regulates platelet activation in nonobese and obese subjects by using methods mimicking thrombus formation. Twelve nonobese (aged 42+/-2 years, body mass index 24.0+/-0.4 kg/m(2)) and 14 obese (aged 43+/-1 years, body mass index 37.2+/-1.5 kg/m(2)) subjects were studied under euglycemic hyperinsulinemic (3-hour insulin infusion of 1 mU. kg(-1). min(-1)) conditions. Before and at the end of hyperinsulinemia, the following were determined: (1) platelet-related early hemostasis (shear rate of approximately 4000 s(-1)) by platelet function analysis; (2) platelet deposition to collagen during whole-blood perfusion (shear rate of 1600 s(-1)); (3) aggregation responses to collagen, thrombin receptor-activating peptide, ADP, and epinephrine; and (4) platelet cGMP concentrations. Insulin action on glucose metabolism was 69% lower in the obese subjects (1.6+/-0.2 mg. kg(-1). min(-1)) than in the nonobese subjects (5.4+/-0.4 mg. kg(-1). min(-1), P<0.0001). The in vivo insulin infusion inhibited platelet deposition to collagen from 4.3+/-0.6x10(6) to 3.5+/-0.4x10(6) per square centimeter in the nonobese subjects (P<0.05) but failed to do so in the obese subjects (5.2+/-0.8x10(6) versus 5.5+/-0.7x10(6) per square centimeter, P=NS; P<0.01 versus nonobese subjects). Epinephrine- and ADP-primed closure times by platelet function analysis were prolonged by insulin in the nonobese but not the obese subjects (P<0.05 for between-group difference). In the nonobese subjects, insulin decreased aggregation to all agonists and significantly increased platelet cGMP concentrations (2.5+/-0.3 versus 3.2+/-0.5 pmol/10(9) for before versus after insulin, respectively; P<0.01). In the obese subjects, insulin did not alter collagen-induced aggregation or cGMP concentrations (1.9+/-0.2 versus 1.8+/-0.1 pmol/10(9) for before versus the end of in vivo hyperinsulinemia, respectively; P=NS). These data demonstrate that normal in vivo insulin action inhibits platelet interaction with collagen under conditions mimicking thrombus formation and reduces aggregation to several agonists. These platelet-inhibitory actions of insulin are blunted or absent in obese subjects and could provide 1 mechanism linking insulin resistance to atherothrombotic disease.