Periodontitis and Cardiovascular Diseases. Consensus Report.

Background: In Europe cardiovascular disease (CVD) is responsible for 3.9 million deaths (45% of deaths), being ischaemic heart disease, stroke, hypertension (leading to heart failure) the major cause of these CVD related deaths. Periodontitis is also a chronic non-communicable disease (NCD) with a high prevalence, being severe periodontitis, affecting 11.2% of the world's population, the sixth most common human disease. Material and Methods: There is now a significant body of evidence to support independent associations between severe periodontitis and several NCDs, in particular CVD. In 2012 a joint workshop was held between the European Federation of Periodontology (EFP) and the American Academy of Periodontology to review the literature relating periodontitis and systemic diseases, including CVD. In the last five years important new scientific information has emerged providing important emerging evidence to support these associations. Results and Conclusions: The present review reports the proceedings of the workshop jointly organised by the EFP and the World Heart Federation (WHF), which has updated the existing epidemiological evidence for significant associations between periodontitis and CVD, the mechanistic links and the impact of periodontal therapy on cardiovascular and surrogate outcomes. This review has also focused on the potential risk and complications of periodontal therapy in patients on anti thrombotic therapy and has made recommendations for dentists, physicians and for patients visiting both the dental and medical practices.

Aspirin withdrawal in patients treated with ticagrelor presenting with non-ST elevation myocardial infarction.

Essentials Strong P2Y12 blockade may cause platelet inhibition that is only minimally enhanced by aspirin. We evaluated aspirin withdrawal on platelet reactivity in ticagrelor treated patients. Aspirin withdrawal resulted in increased platelet reactivity to arachidonic acid. Aspirin withdrawal caused little difference in adenosine diphosphate-induced platelet aggregation. SUMMARY: Background Recent studies have shown that the thromboxane A2 -dependent pathway is dependent on the ADP-P2Y12 pathway, and that strong P2Y12 receptor blockade alone causes inhibition of platelet aggregation that is minimally enhanced by aspirin. Data from the PLATO trial suggested that, among ticagrelor-treated patients, high-dose versus low-dose (< 100 mg day-1 ) aspirin is associated with an increased risk fof ischemic events. Objectives To evaluate the impact of aspirin withdrawal on platelet reactivity in acute coronary syndrome (ACS) patients treated with a potent P2Y12 blocker. Patients/Methods This was a current prospective, randomized, placebo-controlled, double-blind, cross-over study. The study population comprised 22 consecutive ACS patients who underwent percutaneous coronary intervention and were treated with aspirin (100 mg day-1 ) and ticagrelor. Thirty days post-ACS, open-label aspirin was stopped, and patients were randomized to either blinded aspirin or placebo for 2 weeks, with each patient crossing over to the other arm for an additional 2 weeks. Platelet reactivity to arachidonic acid and ADP determined with light-transmission aggregometry (LTA) and VerifyNow was evaluated at baseline, and 2 weeks and 4 weeks later. Results Aspirin withdrawal resulted in an increase in arachidonic-acid induced platelet reactivity as determined with both LTA (77.0% ± 11.3% versus 20.8% ± 4.4%) and VerifyNow (607.7 ± 10.6 aspirin reaction units [ARU] versus 408.5 ± 14.4 ARU). Platelet response to ADP, as determined with both LTA and VerifyNow, did not differ with either aspirin or placebo (32.9% ± 2.6% versus 35.8% ± 3.6%, and 33.5 ± 6.4 P2Y12 reaction units (PRU) versus 29.6 ± 5.7 PRU, respectively). Conclusions Aspirin withdrawal early post-ACS results in increased platelet reactivity in response to arachidonic acid, despite concomitant treatment with the potent P2Y12 blocker ticagrelor.

Obese adults with primary growth hormone resistance (Laron Syndrome) have normal endothelial function.

OBJECTIVE: Classic Laron Syndrome (LS) is a recessive disease of insulin-like growth factor I (IGF-I) deficiency and primary growth hormone insensitivity, clinically characterized by dwarfism and marked obesity. The aim of the current study was to investigate the impact of long-term IGF-I deficiency on flow-mediated dilation (FMD) in 11 non-IGF-I-treated LS adults with long-term IGF-I deficiency who on stress echocardiography were found to have reduced cardiac dimensions and output, but normal left ventricular (LV) ejection fraction at rest and LV contractile reserve following stress. DESIGN: Following an overnight fast we assessed percent improvement in endothelium-dependent FMD (%FMD) and endothelium-independent nitroglycerin (%NTG)-mediated vasodilation non-invasively in the brachial artery, using high resolution ultrasound in 11 non-treated adult patients with LS without known coronary artery disease, and compared them to 11 age- and sex-matched healthy controls. All subjects underwent symptom-limited exercise testing (Bruce protocol). RESULTS: LS patients had a significantly higher body mass index (29+/-6 vs. 25+/-2 kg/m(2), p=0.04), lower low-density lipoprotein cholesterol (142+/-28 vs. 176+/-12 mg/dl, p=0.03) and a smaller mean brachial artery diameter (4.63+/-0.72 vs. 5.70+/-1.06 mm, p=0.01) compared to controls. However, brachial artery %FMD and %NTG were not significantly different between the LS patients and controls (13.1+/-6.2% vs. 15.4+/-5.2%, p=0.28 and 22.3+/-6.0% vs. 18.9+/-6.2%, p=0.30; respectively). Cardiac performance, assessed by exercise duration time and metabolic equivalents (METs), was significantly greater in control subjects than in LS patients (10.3+/-2.0 vs. 6.0+/-1.4 min, p<0.01 and 10.2+/-2.0 vs. 7.2+/-1.4 METs, p<0.01; respectively). CONCLUSIONS: FMD was found to be within normal limits in non-IGF-I-treated adult patients with LS, despite congenital absence of IGF-I and obesity.

Oral magnesium therapy, exercise heart rate, exercise tolerance, and myocardial function in coronary artery disease patients.

BACKGROUND: Previous studies have demonstrated that in patients with coronary artery disease (CAD) upward deflection of the heart rate (HR) performance curve can be observed and that this upward deflection and the degree of the deflection are correlated with a diminished stress dependent left ventricular function. Magnesium supplementation improves endothelial function, exercise tolerance, and exercise induced chest pain in patients with CAD. PURPOSE: We studied the effects of oral magnesium therapy on exercise dependent HR as related to exercise tolerance and resting myocardial function in patients with CAD. METHODS: In a double blind controlled trial, 53 male patients with stable CAD were randomised to either oral magnesium 15 mmol twice daily (n = 28, age 61+/-9 years, height 171+/-7 cm, body weight 79+/-10 kg, previous myocardial infarction, n = 7) or placebo (n = 25, age 58+/-10 years, height 172+/-6 cm, body weight 79+/-10 kg, previous myocardial infarction, n = 6) for 6 months. Maximal oxygen uptake (VO2max), the degree and direction of the deflection of the HR performance curve described as factor k<0 (upward deflection), and the left ventricular ejection fraction (LVEF) were the outcomes measured. RESULTS: Magnesium therapy for 6 months significantly increased intracellular magnesium levels (32.7+/-2.5 v 35.6+/-2.1 mEq/l, p<0.001) compared to placebo (33.1+/-3.1.9 v 33.8+/-2.0 mEq/l, NS), VO2max (28.3+/-6.2 v 30.6+/-7.1 ml/kg/min, p<0.001; 29.3+/-5.4 v 29.6+/-5.2 ml/kg/min, NS), factor k (-0.298+/-0.242 v -0.208+/-0.260, p<0.05; -0.269+/-0.336 v -0.272+/-0.335, NS), and LVEF (58+/-11 v 67+/-10%, p<0.001; 55+/-11 v 54+/-12%, NS). CONCLUSION: The present study supports the intake of oral magnesium and its favourable effects on exercise tolerance and left ventricular function during rest and exercise in stable CAD patients.

Oral magnesium therapy improves endothelial function in patients with coronary artery disease.

BACKGROUND: Magnesium blocks many of the physiological actions of calcium. Nevertheless, the impact of magnesium supplementation on endothelial function and exercise tolerance in stable coronary artery disease (CAD) patients has not been assessed. METHODS AND RESULTS: In a randomized, double-blind, placebo-controlled trial, 50 stable CAD patients (41 men and 9 women, mean+/-SD age 67+/-11 years, age range 42 to 82 years) were randomized to receive either magnesium (n=25) (30 mmol/d Magnosolv-Granulat; Asta Medica Company, Inc) or placebo (n=25) for 6 months. Before and after 6 months, endothelium-dependent brachial artery flow-mediated vasodilation (FMD) and endothelium-independent NTG-mediated vasodilation were assessed with high-resolution (10-MHz) ultrasound. Exercise stress testing was performed with use of the Bruce protocol. Intracellular magnesium concentrations ([Mg(2+)](i)) were assessed from sublingual cells through x-ray dispersion (EXA) (normal mean+/-SD values 37. 9+/-4.0 mEq/L). The magnesium therapy significantly increased postintervention ([Mg(2+)](i) versus placebo (36.2+/-5.0 versus 32.7+/-2.7 mEq/L, P<0.02). There was a significant correlation in the total population between baseline [Mg(2+)](i) and baseline FMD (r=0. 48, P<0.01). The magnesium intervention resulted in a significant improvement in postintervention FMD (15.5+/-12.0%, P=0.02 compared with baseline), which was not evident with placebo (4.4+/-2.5%, P=0.78 compared with baseline). There was better exercise tolerance (9.3+/-2.0 versus 7.3+/-3.1 minutes, P=0.05) and less ischemic ST-segment changes (4 versus 10 patients, P=0.05) in the magnesium versus placebo groups, respectively. CONCLUSIONS: Oral magnesium therapy in CAD patients is associated with significant improvement in brachial artery endothelial function and exercise tolerance, suggesting a potential mechanism by which magnesium could beneficially alter outcomes in CAD patients.

Blood glucose and platelet-dependent thrombosis in patients with coronary artery disease.

OBJECTIVES: To investigate the influence of blood glucose on platelet-dependent thrombosis (PDT). BACKGROUND: Elevated blood glucose is a predictor of adverse cardiovascular risk independent of a diagnosis of diabetes, possibly due to adverse effects promoting thrombosis. The effects of blood glucose on PDT have not been characterized. METHODS: An ex vivo extracorporeal perfusion protocol was used to measure PDT in 42 patients with stable coronary artery disease (CAD). The Badimon chamber was perfused with unanticoagulated venous blood and PDT evaluated using computerized morphometry. Whole blood impedance aggregometry and flow cytometry evaluated platelet aggregation and P-selectin expression, respectively. RESULTS: Using a multivariate stepwise regression model, blood glucose was the best independent predictor of PDT (R2 = 0.19, p < 0.008), followed by apolipoprotein B (R2 = 0.18, p = 0.002) and intracellular magnesium levels (R2 = 0.12, p = 0.02). Platelet-dependent thrombosis was significantly greater in patients with blood glucose >, compared with <, the median value of 4.9 mmol/l (159 +/- 141 vs. 67 +/- 69 microm2/mm, p < 0.01). Neither platelet aggregation nor P-selectin expression was significantly different between the two groups. Insulin levels correlated with blood glucose (r = 0.56, p = 0.0003), but were not independently associated with either PDT, platelet aggregation or P-selectin expression. A two-way analysis of variance demonstrated an interaction between insulin (>126 pmol/l) and blood glucose (>4.9 mmol/l) in modulating PDT (F [1,38] = 8.5, p < 0.006). CONCLUSIONS: Blood glucose is an independent predictor of PDT in stable CAD patients. The relationship is evident even in the range of blood glucose levels considered normal, indicating that the risk associated with blood glucose may be continuous and graded. These findings suggest that the increased CAD risk associated with elevated blood glucose may be, in part, related to enhanced platelet-mediated thrombogenesis.

Additional ST segment elevation during the first hour of thrombolytic therapy: an electrocardiographic sign predicting a favorable clinical outcome.

OBJECTIVES: The aim of this study was to investigate the significance of further ST elevation that occurs during the 1st h of thrombolytic therapy before the expected resolution. BACKGROUND: Early resolution of ST segment elevation is commonly accepted as a marker of clinical reperfusion during thrombolytic therapy for acute myocardial infarction. Using frequent electrocardiographic recordings, we observed in some patients further ST elevation that occurred during hour 1 of thrombolysis before the expected resolution. METHODS: To investigate the significance of this pattern, we classified 177 consecutive patients with a first acute myocardial infarction into two groups: Group A, 98 patients with ST elevation > or = 1 mm above the initial ST elevation during the 1st h of thrombolytic therapy, and Group B, 79 patients without this finding. RESULTS: Although the presence or absence of additional ST elevation was not associated with a clinical or prognostic difference in patients with a first inferior or posterior acute myocardial infarction, its presence indicated a more favorable clinical outcome and prognosis in patients with anterior infarction. Among the patients with anterior infarction the 65 patients in Group A had a higher ejection fraction (44 +/- 9% vs. 35 +/- 11%, p < 0.01), less heart failure (15% vs. 35%, p = 0.02) and a lower in-hospital mortality rate (0% vs. 8%, p = 0.04) than did the 37 patients from Group B. CONCLUSIONS: Additional ST elevation early during thrombolytic therapy in patients with anterior infarction suggests a favorable clinical outcome and thus may be indicative of successful reperfusion.

Intravenous magnesium in experimental stent thrombosis in swine.

We investigated the effects of magnesium on acute platelet-dependent stent thrombosis in an ex vivo porcine arteriovenous shunt model of high-shear blood flow. Control nitinol stents were expanded to 2 mm in diameter in a tubular perfusion chamber interposed in the shunt and exposed to flowing arterial blood at a shear rate of 2100 s(-1) for 20 minutes (n=156 perfusion runs in 10 swine). Animals were treated with intravenous heparin or MgSO(4) alone (2 g bolus over 20 minutes, followed by 2 g/h infusion) and combined heparin plus MgSO(4) in random fashion. Effects on thrombus weight (TW), platelet aggregation, bleeding time, activated clotting time, mean arterial blood pressure, and heart rate were quantified. Data points in the magnesium-treated animals were examined within 20 minutes after bolus (Mg-early) and >40 minutes after bolus (Mg-late). Stent TW (20+/-3 mg, pretreatment) was reduced by 42+/-21%, 47+/-19%, 48+/-16%, 67+/-12%, and 86+/-8% in the groups treated with Mg-early alone, Mg-late alone, heparin alone, heparin+Mg-early, and heparin+Mg-late, respectively (all P<0.001 versus pretreatment, P<0.001 for heparin+Mg-early and Mg-late versus heparin or magnesium alone, and P<0.05 for heparin+Mg-late versus heparin+Mg-early, ANOVA). Magnesium had no significant effect on platelet aggregation, activated clotting time, or bleeding time. There were no significant effects on heart rate or mean arterial blood pressure. The serum magnesium level was inversely correlated with TW (r=-0.70, P=0.002). In conclusion, treatment with intravenous MgSO(4) produced a time-dependent inhibition of acute stent thrombosis under high-shear flow conditions without any hemostatic or significant hemodynamic complications. Thus, magnesium may be an effective agent for preventing stent thrombosis.

Magnesium therapy in acute myocardial infarction when patients are not candidates for thrombolytic therapy.

Thrombolytic therapy reduces in-hospital mortality. However, 70% to 80% of patients do not receive thrombolysis and their in-hospital mortality is high. During the last decade some clinical trials demonstrated that magnesium sulfate reduced in-hospital mortality. The aim of this study was to evaluate the effects of magnesium sulfate in patients with acute myocardial infarction (AMI) who were considered unsuitable for thrombolytic therapy. Intravenous magnesium sulfate was evaluated in 194 patients with AMI ineligible for thrombolytic therapy in a randomized, double-blind, placebo-controlled study. Group I consisted of 96 patients who received 48-hour intravenous magnesium. Group II consisted of 98 patients who received isotonic glucose as a placebo. Magnesium reduced the incidence of arrhythmias, congestive heart failure, and conduction disturbances compared with placebo (27% vs 40%, p = 0.04; 18% vs 23%, p = 0.27; 10% vs 15%, p = 0.21, respectively). Left ventricular ejection fraction 72 hours and 1 to 2 months after admission was higher in patients who received magnesium sulfate than in those taking placebo (49% vs 43% and 52% vs 45%; p = 0.01, respectively). In-hospital mortality was significantly reduced in patients receiving magnesium sulfate than in those receiving placebo (4% vs 17%; p < 0.01), and also in the subgroup of elderly patients (> 70 years) (9% vs 23%; p = 0.09). In conclusion, magnesium sulfate should be considered as an alternative therapy to thrombolysis in patients with AMI.

Beneficial effect of magnesium sulfate in acute myocardial infarction.

The effects of magnesium on the incidence of arrhythmias and on mortality were evaluated in 103 patients with documented acute myocardial infarction (AMI) in a randomized, double-blind, placebo-controlled study. Fifty patients received a magnesium infusion for 48 hours and 53 received only the vehicle (isotonic glucose) as placebo. The baseline characteristics of the population were similar in the 2 groups. Tachyarrhythmias requiring drug therapy were recorded in 32% of the patients in the magnesium group and in 45% of the placebo group. Conduction disturbances were found in 23% of the placebo group as compared to 14% in the magnesium group. The intrahospital mortality was 2% (1 patient) in the magnesium group, compared to 17% (9 patients) in the placebo group (p less than 0.01). No adverse effects were observed during and after the magnesium infusion. These data support a possible protective role of magnesium in patients with AMI.

Improvement in endothelium-dependent brachial artery flow-mediated vasodilation with low-density lipoprotein cholesterol levels <100 mg/dl.

To determine whether the current National Cholesterol Education Program cholesterol recommendations are consistent with beneficial endothelium-dependent vasodilation, we prospectively assessed endothelium-dependent brachial artery vasoreactivity in 50 patients with stable coronary artery disease. Our results showed that endothelial-dependent vasoreactivity was greater when low-density lipoprotein cholesterol was <100 mg/dl, suggesting that it may be beneficial to reach the National Cholesterol Education Program Adult Treatment Panel II target of low-density lipoprotein cholesterol of <100 mg/dl.

Oral magnesium supplementation inhibits platelet-dependent thrombosis in patients with coronary artery disease.

The use of magnesium in the treatment of acute myocardial infarction remains controversial despite preliminary experimental evidence that magnesium plays a beneficial role as a regulator of thrombosis. This study examines whether oral magnesium treatment inhibits platelet-dependent thrombosis (PDT) in patients with coronary artery disease (CAD). In a randomized prospective, double-blind, crossover, and placebo-controlled study, 42 patients with CAD (37 men, 5 women, mean age 68 +/- 9 years) on aspirin received either magnesium oxide tablets (800 to 1,200 mg/day) or placebo for 3 months (phase 1) followed by a 4-week wash-out period, and the crossover treatment for 3 months (phase 2). PDT, platelet aggregation, platelet P-selectin flow cytometry, monocyte tissue factor procoagulant activity (TF-PCA), and adhesion molecule density were assessed before and after each phase. PDT was evaluated by an ex vivo perfusion model using the Badimon chamber. Median PDT was significantly reduced by 35% in patients who received magnesium versus placebo (delta change from baseline -24 vs 26 mm2/mm; p = 0.02, respectively). There was no significant effect of magnesium treatment on platelet aggregation, P-selectin expression, monocyte TF-PCA, or adhesion molecules. Oral magnesium treatment inhibited PDT in patients with stable CAD. This effect appears to be independent of platelet aggregation or P-selectin expression, and is evident despite aspirin therapy. These findings suggest a potential mechanism whereby magnesium may beneficially alter outcomes in patients with CAD.

Frequency and prognostic significance of secondary ventricular fibrillation complicating acute myocardial infarction. SPRINT Study Group.

The incidence of secondary ventricular fibrillation (VF) complicating acute myocardial infarction (AMI) was 2.4% in a large cohort of unselected patients with AMI (142 of 5,839). Secondary VF was more frequent in patients with recurrent AMI (4%) than in those with a first AMI (1.9%) (p < 0.01). The hospital course was more complicated and in-hospital mortality was significantly higher in patients with secondary VF than in those with the same clinical hemodynamic condition but without VF (56 vs 16%; p < 0.0001). Multivariate analyses confirmed secondary VF complicating AMI as an independent predictor of high in-hospital mortality, with an odds ratio of 7 (95% confidence interval 4.6-10.6). However, long-term mortality after discharge (mean follow-up 5.5 years) was not increased in patients with as compared with those without secondary VF (39 vs 42%). These findings were also true when patients receiving beta blockers and antiarrhythmic therapy were excluded from analysis. Thus, this life-threatening arrhythmia occurring during hospitalization is not a marker of recurrent susceptibility to VF or an indicator of increased mortality after discharge from the hospital.

Contingent valuation of supplemental health care in Israel.

The use of the contingent-valuation method for determining willingness to pay for non-market or currently available health care services continues to be experimental. In this study, the contingent-valuation method was used to calculate willingness-to-pay estimates for a proposed change in the Israeli health care system. It was found that the willingness-to-pay estimates calculated in the Israel study were reasonable and that the methodology is able to adapt to the special nature of the health care commodity while adhering to the conditions for reliability and validity in a contingent-valuation study.

Occult aortic arch mycotic aneurysm diagnosed by radiogallium scintigraphy.

Aortic arch mycotic aneurysm, an uncommon cause of sepsis, carries a grave prognosis. Clinical presentations as well as laboratory and radiologic examinations may be noncontributory and often misleading. In a patient with a fever of unknown origin, only the radiogallium study could enable an accurate diagnosis and pinpoint the anatomic localization of the mycotic aneurysm as the cause of fever.

Beneficial antithrombotic effects of the association of pharmacological oral magnesium therapy with aspirin in coronary heart disease patients.

The use of magnesium in the treatment of acute myocardial infarction remains controversial despite preliminary experimental evidence that magnesium plays a beneficial role as a regulator of thrombosis. The aim of our study was to determine whether oral magnesium treatment inhibits platelet-dependent thrombosis (PDT) in stable patients with coronary artery disease (CAD). In a randomized prospective, double-blind, cross-over and placebo controlled study, 42 patients with stable CAD (37 men, 5 women, mean age 68 +/- 9 years) on aspirin received either magnesium oxide tablets (800-1,200 mg/day) or placebo for 3 months (Phase 1) followed by a 4-week washout period, and the cross-over treatment for 3 months (Phase 2). PDT, platelet aggregation, platelet P-selectin flow-cytometry, monocyte tissue factor procoagulant activity (TF-PCA) and adhesion molecules density were assessed before and after each phase. PDT was evaluated by an ex-vivo perfusion model using the Badimon chamber. Median PDT was significantly reduced by 35 percent in patients who received magnesium versus placebo (D change from baseline: -24 vs. 26 microm2/mm; p = 0.02, respectively). There was no significant effect of magnesium treatment on platelet aggregation, P-selectin expression, monocyte TF-PCA or adhesion molecules. Oral magnesium treatment inhibits PDT in patients with stable CAD. This effect appears to be independent of platelet aggregation or P-selectin expression, and is evident despite aspirin therapy. These findings suggest a potential mechanism whereby magnesium may beneficially alter outcomes in patients with CAD.

Anxiety: towards a decision-theoretic perspective.

This paper sets out to illustrate how anxiety may be incorporated into a formal decision theoretic utility model of choice, and to suggest several measurement procedures towards that end. The major propositions derived and posited in this paper lend considerable support to intuitive notions with respect to the effects of anxiety on human behaviour in risky decision situations. Namely, that the willingness of an individual to pay to reduce health risks (an economic indicator of individual welfare associated with reduced morbidity or increased longevity) tends to be positive and higher when anxiety is present than when it is not. The formal results of the analysis show that when psychological considerations are incorporated into a state-dependent utility model, the normative results customarily obtained concerning value-of-life need to be qualified.

Increased mean platelet volume is associated with non-responsiveness to clopidogrel.

Prior studies have demonstrated significant individual variability of platelet response to clopidogrel, which affects clinical outcome. In patients with stable coronary artery disease (CAD) smoking, diabetes mellitus, elevated body mass index and renal insufficiency, significantly impact response to clopidogrel. The determinants of platelet response to clopidogrel in patients with acute coronary syndrome are unknown. Adenosine diphosphate (ADP)-induced platelet aggregation (PA), hs C-reactive protein, platelet count and mean platelet volume (MPV) were determined 72 hours post clopidogrel loading in 276 consecutive acute myocardial infarction (AMI) patients. Patients with ADP-platelet aggregation ≥ 70% were considered to be clopidogrel non-responders. Eighty-four patients (30%) were clopidogrel non-responders and 192 (70%) were responders (ADP-induced PA: 81 ± 17% vs 49 ± 17%, respectively, p<0.001). Both study groups were comparable with respect to age, gender, prior cardiovascular history, prior aspirin use and risk factors for CAD, including smoking (42% for both groups) and diabetes mellitus (26% vs 22%, respectively, p=0.4). Responders and non-responders had similar angiographic characteristics, indices of infarct size, and similar hs-CRP (29 ± 34 vs 28 ± 34 mg/l, p=0.7) and creatinine (1.08 ± 0.4 mg% vs 1.07 ± 0.4, p=0.9) levels. On the contrary non-responders had significantly larger mean MPV (9 ± 1.2 fl vs 8 ± 1 fl, respectively, p=0.0018), and when patients were stratified into quartiles based on MPV, ADP-induced PA increased gradually and significantly across the quartiles of MPV (p<0.001). In conclusion, increased MPV associated with platelet activation, predicts non-responsiveness to clopidogrel among patients with acute coronary syndrome.