Bui, Minh N.

Cannon, Richard O.

Caulfield, Michael T.

Katz, Paul

Rackley, Charles E.

Elsevier - Publisher Connector 

JACC Fdorus~ 1996 ABSTRACTS-Poster 413A 
In the overall control patients, 113.20 :b 89.8% In the matched control patients 
(p < 0.01; patients w~h high Lp{e) levels ve overall and matched conVols). 
Maximal Inoreasos In the coronary diameter had nsgative correlations with 
Lp(a) levels (p < 0.05, r - -O.25 and -0.35; ~te  with thgh Lp(a) k~s  ve 
overall and matched controls, respo,~aly). Maximal Increases In the com- 
naly blood flow had also negative collations with Lp(a) levels (p < 0.01, r 
= -0.31 and -0.48, patients with hk]h Lp(a) levels ve overall and matched 
controls, respectively). These results suggested elevated Lp(a) levels impair 
endothallum.dependent vasodilster response, which may conifibute to ac- 
celera~d athemgenlo r ~rombogenls ~ In pa~ents with hlgh Lp(a) 
tevels, 
~ Comparat ive Effect of  Pravaststln and 
S lmvuts t ln  on Platelet.Thrombus Formation In 
Hypercholaslerolemlc Coronary Pal lents 
Lucle Lacoete, Jules Y.T. Lain. Montreal Heart Institute, Monlmal, Quebec, 
Can~ 
High cholesterol (¢hol) is a risk factor for coronary atherosClerOsls and re- 
ducing elevated cholesterol has been shown to prevent coronary morblo~ly 
and moriardy. Hypercholastomlemic pts also have hyperactive platslets and 
an increased tendency to platelet-thmmbus formation at the site of an in- 
jured artedal wall. This pmthombot~e t ndency may favor the development 
of acute Ischemic coronary ovens due to coronanj thrombosis at the site of 
plaque rupture. Whether, reduction of serum cholesterol with the HMG-CoA 
reduclase inhlbitom, pravastatin (Pmva) or slmvastatin (Simva), will intiuenca 
pletslet thrombosis In stable coronary pts taking aspldn, 325 mg/day, was 
assessed before and after 2-3 months of Prava therapy (40 rag/day, n = 16) 
or Simva therapy (20 rag/day, n = 16). Platelet thrombos fonaation (PT) was 
evaluated by exposing porolna aortic media (simulating deep arterial Injury) 
to the pt's flowing venous blood for 3 rain at shear rates of 2546 and 754 
s "1 at 3"FC in a superlusicn chamber ex vive. Serum lipide and quantita- 
tive marphometne PT (izn~'lmm) before and after drug tma~-nsnt are shown 
below: 
Shear ate Basal Prays Basal Simva 
PT: 2546 **-1 2.0±0.4 1.0 4. 0.2 "? ;!.1 4-0A 2.04-0.4 
7548 -1 1.7.~0.4 0.94-0.1"t 1.8~0.4 1.84-0.4 
Chat: Tolal 6.1 4-0.1 4.6 :t: 0.2" 5.5::1:0.3 4.7 ± 0.2" 
(mmol~.) LDL 4.1 4-0.1 2.84-0.1" 4.54-0,3 2.84-0.2* 
• p < 0.05 vs basal, l";p < 0.05 vs SImva 
Thus, both Simva and Prave decreased somm total and LDL cholesterol, 
but pletstet hrombosis was inhibited mare by preva at both the high and low 
shear rates tested. These resu~ suggest that after 2-3 months of therapy, 
HMG-CoA reductase inhibitom may have a differential effect on platelet 
thrombosis which may influence the early clinico-pethotegic evolution of the 
coronary atherosolaro~c process. 
• Pl~:e. nt Cholesterol Absorpt ion in Normal Human 
~ublec'ts by Negative Ion Gas Chromatography 
Mass Spectrometry 
Matthew S. Besnar, William Sfanson, Pat~ Tumbough, Stephen Block, 
Laura Koboyashi, Abigail Schweizar, R ~  E. Oetlund, Jr.. Jewish 
Hospital and Wash~ton University School of Medicine, St. Louis, MO 
Percent cholesterol (CH) absoq~tion was measured in 70 normal subjects on 
their ambient diet by simultaneous adminlslration of 30 mg CH [23,24,25,26, 
2.~3-C5..-GH orally v~ a standard meal and 15 tag [26,26,26,27,2-/, 
-H6-CH IV. Blood was collected on days 0 and 3, CH isolated, and 
darivalized to a pent~uorobenzoyl ester, and the ratio of isotopic tracer ana- 
lyzed by negative ion gas chromatography mass epecVomeW. The resulting 
mass spectra consisted almost solely of intense molecular GH lens pem~it- 
ling detection of 20 final of tracer. Percent CH absoq~icn was 56.8 + 11.5% 
(mean 4- SO, N = 70, age 18 to B2 years, 51 female, 19 male), confkmlng 
heterogeneity of CH absoq)tion In normal humans. CH absoq~don was not 
re.ted tO age, gender, plasma, llp[ds or apepreteln levels including apo-E 
genotype (by PCR). Chronic dietary calories, dtetanj % fat or CH composition. 
or fiber quantitstsd from 7-day food records were not related to CH. CH was 
signlrcangy negatively correlated with plasma insulin (r = -0.250, p = 0.549) 
and plasma ~t ide  (-0.25, p ,, 0.0079). Thus percent CH absorption may 
be regulated by insulin and altered by insulin resistance. The SD between 
tests performed 4-6 weeks apart was 2.8% suggesting stability over time. 
This novel and broadly applicable method may provide a precise technique 
to quanl~ Inten~antiona such as ~et or o'nJgs on CH absor~on in humans. 
~ Immune Responses to HMG-CoA Reductase 
Inhlbltors in Patients With Abnormal  Upid Level 
Minh N. Bul, Mk'haal 1". Caulflald, Paul Kalz, Richard O. Cannon III, Charles 
E, Reckley. Georgetown Univers~ Medical Center, Washington, DC; 
NHLBI, NIH, Bethesda, MD 
Gflnloal trials with HMG-COA reductssa Inhlbitom have reported decrease In 
clinical events out of proportion to small anatomical changes In coronary an- 
glogmm, Previous finding from our lab has shown that HMG-COA reduclasa 
inhlbltere cause a rise in IDG autoantibodies to oxidized LOL(ox-LDi) during 
the first 6 months of therapy. However, the autoantibodles tilers decrease by 
t2 months. We examined the potential Immune response in hypedipldemlc 
patients treated with HMG-COA reductase inhibitom, A nonlsotopta EUSA 
technique was used to measure autoantibodies titem in 11 I~tients with 
hypefllpldemla. LDL, IgG and IgM autoantibodles titem were measured at 
baseline and at 4 d: 1.4 months after tma~nent with HMG-COA mdu,~tese 
fnhlbitom. 
Baseline 4 months 
LOt. (rag/d1) 17~. 4. 37 138 :)= 28" 
Autoantn)odles to ox.LDI. (OD) 
IgG 0.1384- 0.076 0.1544.0.087 
IgM 0.0244-0.019 0.053 d: 0.044" 
• p-value < 0.0S vs. baseline by paired Student t-teal; OD: optfcat density 
Conclusion: 1) A decrease in LDL level was associated with an Inc~eese in 
eutoantibodies tltom to ox-LOL. 2) Early In~'ease in autoantibodles titsrs was 
greater with tgM than IgG. 3) These early immune responses may contribute 
to plaque stabilization. 


Immune responses to HMG-CoA reductase inhibitors in patients with abnormal lipid level 

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Immune responses to HMG-CoA reductase inhibitors in patients with abnormal lipid level

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