RT Journal Article
SR Electronic
T1 53 CARDIOVASCULAR EVENTS ≤ AGE 45: ATHEROTHROMBOSIS.
JF Journal of Investigative Medicine
JO J Investig Med
FD BMJ Publishing Group Ltd
SP S357
OP S357
DO 10.1136/jim-55-02-53
VO 55
IS 2
A1 J. Munjal
A1 G. J. Charles
A1 D. M. Aregawi
A1 P. Wang
YR 2007
UL http://hw-f5-jim.highwire.org/content/55/2/S357.2.abstract
AB The population that develops occlusive arterial circulatory events at a young age (≤ 45 years), particularly if they are normolipidemic, represents a rare population in which a heightened hemostatic system may play an important mechanistic role in thrombus formation and in arterial events. We assessed whether thrombophilia-hypofibrinolysis contributed to premature atherothrombotic cardiovascular disease (ATCVD) in 78 men and 40 women with 230 ATCVD events (≤ age 45 years). ATCVD events included ≥ 1 myocardial infarction (n = 60), CABG (n = 33), angioplasty (n = 52), chronic angina (n = 41), ischemic stroke (n = 11), TIA (n = 24), and claudication (n = 9). Hereditary thrombophilia was assessed: G1691A factor V Leiden, G20210A prothrombin, MTHFR C677T-A1298C, and platelet glycoprotein PL A1/A2 mutations, with serologic measures of ACLA IgG and IgM, lupus anticoagulant, proteins C and S, antithrombin III, homocysteine, and factors VIII and XI. Hypofibrinolysis was assessed: 4G4G plasminogen activator inhibitor 1 mutation (PAI), PAI activity (PAI-Fx), and Lp(a). Cases were compared with healthy normal controls (149 men for PCR, 40 men for serologic tests, 109 women for PCR and serologic tests). Cases did not differ from controls by race or age (p > .05) Hypertension was present in 44% of men and 25% of women, diabetes in 17% and 8%, and cigarette smoking in 25% and 20%. In the 78 male cases, mean ± SD age was 48 ± 11 years, BMI 29.5 ± 4.5, LDLC 103 ± 44, HDLC 41 ± 14, and TG 195 ± 219 mg/dL. In 40 female cases, mean ± SD age was 38 ± 10 years, BMI 28.3 ± 7.7, LDLC 105 ± 31, HDLC 50 ± 13, and TG 147 ± 121 mg/dL. High factor VIII (> 150%) was present in 15 of 59 (25%) male cases versus 1 of 38 (3%) male controls, p = .003. High factor XI (> 150%) was present in 9 of 56 (16%) male cases versus 0 of 38 (0%) male controls, p = .01. High PAI-Fx (> 21.1 U/mL) was present in 24% of male cases (15 of 63) versus 8% (3 of 39) of male controls, p = .038. Low protein C (< 73%) was present in 4 of 25 (16%) female cases versus 2 of 107 (2%) female controls, p = .012. Low free protein S (< 66%) was present in 5 of 27 (19%) female cases versus 3 of 107 (3%) female controls, p = .009. High factor XI (> 150%) was present in 3 of 26 (12%) female cases versus 2 of 107 (2%) female controls, p = .051. The lupus anticoagulant was present in 9 of 37 (24%) female cases versus 6 of 84 (7%) female controls, p = .014. In patients with ATCVD ≤ age 45, thrombophilias (factor VIII, factor XI, protein C and S deficiency, and the lupus anticoagulant) and hypofibrinolysis (PAI-Fx) may promote arterial thrombosis, synergistic with atherosclerotic endothelial injury. If thrombophilia-hypofibrinolysis accompanies ATCVD at ≤ age 45, thromboprophylaxis may have value in secondary prevention of subsequent ATCVD.