title: Abnormal platelet reactivity in men with premature coronary heart disease.
abstract: BACKGROUND
  Continuous platelet aggregation does not occur in patients with stable coronary heart disease (CHD). However, there may be a latent potential for increased aggregation given appropriate stimuli, since increased in-vitro platelet aggregation appears to be predictive of cardiac events. This study evaluates the relationship between in-vitro platelet aggregation and coronary artery disease (CAD) as defined by angiography.
  
  
  METHODS
  In-vitro platelet aggregation was assessed in a case-control study of 53 men with CHD younger than 50 years, and in 48 control subjects without CHD who were matched for age, sex, and socioeconomic status. All major risk factors were evaluated. Semi-quantitative composite scores of the extent of arterial wall involvement and composite scores for the severity of discrete lesions were documented from standard coronary angiography. Measures of platelet aggregation in response to adrenaline, adenosine diphoshate (ADP), and collagen included: (1) the maximum slope of the aggregation curve (rate); (2) lag time to 50% maximum aggregation (LT50%); and (3) the threshold concentration of each agonist to cause maximal aggregation.
  
  
  RESULTS
  The CHD patients had larger platelets than patients in the control group (mean platelet volume 9.40 +/- 0.73 versus 8.88 +/- 0.87; P < 0.01). The aggregation rate was significantly faster with adrenaline in the group with CHD than patients in the control group (rate of aggregation 13.9 +/- 8.8 versus 8.6 +/- 4.0 cm/s respectively, mean +/- SD; LT50% for adrenaline 130 +/- 70 versus 230 +/- 10 s respectively, mean +/- SD). Fewer CHD patients had no aggregation response to adrenaline than in the control group (8 versus 31%, P < 0.05). Adrenaline-induced platelet aggregation, as measured by LT50% for adrenaline, weakly but significantly correlated with the number and severity of discrete obstructive coronary lesions (r = -0.28, P < 0.05). This association remained significant after multivariate regression analysis. No association was found between any measure of platelet reactivity and the extent of disease as measured by a semi-quantitative composite score; this measured the extent of disease of the coronary artery walls visible by angiography.
  
  
  CONCLUSIONS
  These findings indicate that platelets from men with premature CHD are larger and aggregate more rapidly in response to platelet agonists, particularly adrenaline. An increased rate of aggregability with adrenaline predicted the severity of CAD lesion but not the extent of the disease, and this suggests that platelets play a role in the formation of localized obstructive lesions in coronary arteries, and therefore acute coronary events.
authors.affiliation: Department of Cardiology, Woden Valley Hospital, Australia.
authors.forename: D A
authors.initials: DA
authors.lastname: McGill
authors.forename: N G
authors.initials: NG
authors.lastname: Ardlie
mesh_terms: D000244:Adenosine Diphosphate / Q000494:pharmacology; D000328:Adult; D000367:Age Factors; D001810:Blood Volume / Q000187:drug effects; D016022:Case-Control Studies; D002784:Cholesterol / Q000097:blood; D003094:Collagen / Q000494:pharmacology; D017023:Coronary Angiography; D003327:Coronary Disease / Q000097:blood / Q000150:complications / Q000000981:diagnostic imaging / Q000503:physiopathology*; D004837:Epinephrine / Q000494:pharmacology; D006801:Humans; D008074:Lipoproteins / Q000097:blood; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects* / Q000502:physiology; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D010976:Platelet Count / Q000187:drug effects; D011237:Predictive Value of Tests; D012044:Regression Analysis; D012307:Risk Factors; D012720:Severity of Illness Index; D013929:Thromboxane B2 / Q000097:blood
chemical_list: D008074:Lipoproteins; D010975:Platelet Aggregation Inhibitors; D013929:Thromboxane B2; D000244:Adenosine Diphosphate; D003094:Collagen; D002784:Cholesterol; D004837:Epinephrine