American HeartAssociationsJFighting Heart Disease

and Stroke

ThrombosisFall 1995 Edwin G. Bovill, MD, Editor

Editor's Note 1

Report From the Chair 1

Invited Review 4

Committee and Liaison Reports 6

Announcements 13

Application for Membership 14

Editor's Note

This newsletter addresses anumber of critical issues for mem-bers of the Council on Thrombosis.Dr Thomas Deuel reviews a meetingwith Dr Claude Lenfant, director ofNHLBI, that occurred during theDecember 1994 meeting of theAmerican Society of Hernatology.The meeting with Dr Lenfant fo-cused on ways to improve commu-nication between our council and theNIH. Dr Deuel also gives an Updateon the important ongoing work withrespect to the future of vascularbiology and its role in the AHA.There is serious consideration aboutconsolidation of the Council onThrombosis with the Council on

Arteriosclerosis and the WorkingGroup on Vascular Biology. DrSamuel Rapaport, incoming chair ofthe Thrombosis Council, discussesthis in his report on page 2.Drs Pan Ganguly (Blood) and DavidRobinson (Heart) have replacedDr Carol Letendre äs our liaison withthe NHLBI. Dr Ganguly's reportcovers new initiatives and reviewsrecent changes in funding guide-lines. Dr Kenneth Mann reviews theStatus of the AHA grant System anddiscusses a number of approvedand pending changes. Dr JackHawiger reports that our JournalArteriosclerosis, Thrombosis, andVascular Biology is doing well.

This issue of the newsletter alsoincludes a new feature, an invitedreview of a topical area. Dr FritsRosendaal from the Departments ofClinical Epidemiology and Hernatol-ogy, Leiden, The Netherlands, hascontributed a review entitled "Resis-tance to Activated Protein C byFactor V Leiden: Clinical Implica-tions." Finally, there is a review ofthe programs for the Council onThrombosis at the 1995 ASHmeeting and the 1996 AHA meet-ings along with a report on thebudget for fiscal year 1995-1996.

Edwin G. Bovill, MD

Report From the Chair

Report From Thomas F. Deuel, MD, Immediate Fast Chair

Two most important events need your closest atten-tion.

During the American Society of Hernatology Meeting inDecember, Sam Rapaport and l met for an hour and ahalf with Claude Lenfant, director of the NHLBI. Themeeting was very productive. We primarily discussedways in which the Council on Thrombosis might enhanceCommunications with Dr Lenfant and the NHLBI andmechanisms to maintain the highest levels of communi-cation. Dr Lenfant expressed great interest in theactivities of the Council on Thrombosis and the Commu-nity that it represents. He invited our input into all issuesrelated to the activities of the NHLBI. We discussedchanges in the focus of the Council on Thrombosis thathave evolved over the past several years and empha-sized that many investigators within the council are nowfocusing on issues of vascular biology, atherosclerosis,and cardiovascular disease äs the natural outgrowth ofresearch in hemostasis and thrombosis. The vigor andenergy of these investigators and the importance of theircontributions to an understanding from a variety ofperspectives of phenomena within the blood vessel wallwas stressed. We emphasized the importance ofrecognizing within NHLBI the extent to which contribu-tions of the thrombosis Community could overlap theactivities of the Vascular Biology Program of the Division

of Heart and Vascular Diseases. In response, DrLenfant agreed to appoint Dr David Robinson, director ofthe Vascular Biology Program, äs an additional liaison tothe Council on Thrombosis. Thus, both our presentliaison, Dr Pan Ganguly, leader of the Thrombosis andHemostasis Scientific Research Group within theDivision of Blood Diseases and Resources, and DrRobinson will now work with the council. This is awonderful commitment to us, and we enthusiasticallylook forward to working with both of them. SamRapaport and l hope to meet periodically with Dr Lenfantto maintain a fruitful, continuing interaction between theCouncil on Thrombosis'and the NHLBI.

The second issue of major importance to the Councilon Thrombosis is the future of vascular biology in theAHA. Sam Rapaport, Ralph Nachman, and l repre-sented the Council on Thrombosis on the Task Force onIntercouncil Cooperation, a committee appointed by DrJames Moller, President of the AHA during 1993-1994, tofind ways to integrate activities of the Working Group onVascular Biology, the Council on Thrombosis, and theCouncil on Arteriosclerosis.

The Working Group on Vascular Biology was formed in1991 to address interests related to vascular biology, butits activities will cease in mid-1997. The gain to theCouncil on Thrombosis of merging with the working

group and the Council on Arteriosclerosis would be a farlarger council with far greater impact within the AHA andfar greater opportunities to influence the content ofmeetings äs well. Coordinated programs and activitiescan only enhance our visibility and strength within theAHA and will better serve its mandates for consolidationof councils and coordination of activity. Such a unionwould also help emphasize our areas in the researchCommunity. We plan to have a separate meeting inaddition to the AHA meeting that will represent all threegroups; this will be a highly visible and important meet-ing. However, it will not replace the importance of thecontributions to the annual meeting.

This consolidation of the Councils of Thrombosis andAtherosclerosis with the Working Group on VascularBiology was discussed at great length at the meeting ofthe Executive Committee in May. It was concluded thatsuch a consolidation was highly desirable and consistentwith the long-range goals of the council. It was alsostressed that the needs of the diverse interests ofcouncil members had to be met in füll in order to consoli-date the three groups. The Executive Committeeunanimously voted to bring this matter to füll discussionat the November meeting of the council with the goal ofa vote of the council members to follow.

The opportunities for advancing the cause ofthrombosis are striking but can be done only if membersof the council are enthusiastic and utmost considerationis given to our best interests. l invite your commentsand very much urge each of you to write.

In ciosing, l thank the Council on Thrombosis for theprivilege to serve äs chair. It has been a most rewardingexperience. l look forward to helping Sam Rapaport andBob Rosenberg, the new chair and vice-chair, in any waypossible.

Report From Samuel I. Rapaport, MD,Chair

In July of this year l succeeded Dr Deuel äs chair ofthe Council on Thrombosis. As recommended at theMay 1995 meeting of the Executive Committee, l amproceeding with plans for a proposed merger of theCouncils on Thrombosis and Arteriosclerosis to befollowed by a proposal from a merged council to theWorking Group on Vascular Biology to incorporate theirinterests within a combined Council on Arteriosclerosis,Thrombosis, and Vascular Biology.

In August l wrote a letter to all present and pastmembers of the Executive Committee (since 1988) tosummarize the background of the proposed merger andthe reason why it is necessary for the Executive Com-mittee to decide without delay at its meeting in Anaheimthis November on whether to proceed with the mergerwith the Council on Arteriosclerosis. A copy of this letter,

which includes how to contact me by regulär mail, fax,and e-mail, follows to inform all council members of howwe got to where we are now.

There are many advantages to a proposed combinedlarger council, but there will be issues to resolve äs amerger with the Council on Arteriosclerosis proceeds. Ifyou have specific feelings about the proposal or issues itraises, l invite you to send them to me before theNovember meeting of the Executive Committee.

Since this is our "off year" at the AHA ScientificSessions, l know that many of you will not be present atthe meeting. For those of you who will be there, pleasemake a special effort to attend the business meeting ofthe council, which will be heid at noon on Monday,November 13.

TO: Present and Recent Past Members of theExecutive Committee of the Council onThrombosis

FROM: Samuel l. Rapaport, Chairperson, Councilon Thrombosis

SUBJECT: Proposed Merger With Council onThrombosis and Vascular Biology WorkingGroup

l am writing for two purposes:

(1) To inform you of the Status of considerations for aproposed merger of the Councils on Arteriosclerosis andThrombosis to be followed by a proposal from themerged council to the Vascular Biology Working Groupto incorporate their interests within a combined Councilon Arteriosclerosis, Thrombosis, and Vascular Biology.

(2) To seek advice in defining issues in this regard thatneed advance thought before the forthcoming Council onThrombosis Executive Committee meeting next Novem-ber at the AHA Scientific Sessions in Anaheim.

Two years ago the Counci! Affairs Committee and theSteering Committee of the AHA commissioned a taskforce to examine the current structure of the Councils onArteriosclerosis and Thrombosis, assess the relationshipof vascular biology and the Vascular Biology WorkingGroup of AHA to these councils, and develop options tointegrale and enhance the functions and activities of allthree groups. Drs Scott Grundy and Ken Mann wereappointed by AHA to serve äs cochairs of the task force.Membership included the chairpersons, vice chairper-sons, and immediate past chairpersons of the twocouncils (Drs Deuel, Rapaport, and Nachman for theCouncil on Thrombosis; Drs Small, Grundy, and St. Clair

forthe Council on Arteriosclerosis) and Dr Victor Dzau,chairperson of the Vascular Biology Working Group.

After long discussions at three meetings of pros andcons, the task force recommended that the two councilsand the working group be integrated into a new scientificcouncil structured to accommodate the overlappinginterests of the participating groups. Dr Deuel and l, äsyour representatives on the task force, concurred fullywith this recommendation (Dr Nachman was not presentat the meeting). We believe that the bringing into asingle AHA "scientific tent" of investigators interested indiverse aspects of the pathogenesis and treatment ofthrombotic disorders would have many advantages. Anew scientific council created out of the existing Coun-cils on Arteriosclerosis and Thrombosis and the WorkingGroup on Vascular Biology should have a greater say inthe structure of the scientific program at the annualnational meeting in November. It would support anexpanded scope and influence of our Journal Arterioscle-rosis, Thrombosis, and Vascular Biology. Moreover, thenew amalgamated council should have the critical massneeded to Sponsor a yearly stand-alone meeting onvascular biology in the spring of the year. Indeed, at theinstigation of the task force, a scientific meeting thatcould serve äs a prototype for future spring symposiawill be held in Salt Lake City on February 18-20, 1996[see announcement on page 13]. l hope that many ofyou will participate in this meeting.

After the last meeting of the task force in April 1995,Drs Grundy and Deuel wrote a draft memorandum fromthe task force to the Councils on Arteriosclerosis andThrombosis and the Working Group oin Vascular Biologyproposing the creation of an enlarged and integratedcouncil involving the three groups. This memorandumwas reviewed at the May meeting of the ExecutiveCommittee of the Council on Thrombosis, which washeld in San Diego in conjunction with the clinical meet-ings. At that meeting it was moved, seconded, andcarried that the Council on Thrombosis pursue thefeasibility of an amalgamation äs described in thememorandum. Since a number of members of theExecutive Committee were unable to attend this Maymeeting, l am enclosing with this letter a copy of thememorandum.

In June 1995 Dr Grundy, äs cochair of the task force,reviewed the task force memorandum at a meeting ofthe Council Affairs Committee. A proposed merger ofthe Councils of Arteriosclerosis and Thrombosis evokedno Substantive comment from other council chairspresent at that meeting. Subsequently, Dr Rodman D.Starke, Senior Vice President, Office of Scientific Affairs,advised Dr Grundy, äs chairperson of the Council onArteriosclerosis, and me, äs the incoming chairperson ofthe Council on Thrombosis, that the next step in movingforward a merger of the Councils on Arteriosclerosis andThrombosis would be a vote in favor of such a merger

from the Executive Committee of each council.Dr Grundy informs me that the Executive Committee

of the Council on Arteriosclerosis met earlier this monthand enthusiastically endorsed the recommendation ofthe task force that the Councils on Arteriosclerosis andThrombosis merge and jointly make a proposal forcreation of a new scientific council that will incorporatevascular biology. The Executive Committee of Arterio-sclerosis also recommended that this larger council havethree subsections identified äs (a) lipid and lipoproteinmetabolism, (b) thrombosis, and (c) vascular biology andthat the Executive Committee of the new council becomposed primarily of representatives of these threesubsections.

Working Groups of AHA have a five-year term, whichfor the Working Group on Vascular Biology expires in1997. Therefore, the Vascular Biology Working Groupmust soon decide whether their continuing activitieswithin AHA are best served within a combined Arterio-sclerosis, Thrombosis, Vascular Biology Council. At theJune meeting of the Council Affairs Committee, chairper-sons of several other councils expressed interest in thefuture of the Vascular Biology Working Group. A realpossibility exists that the working group will receivewithin the next several months competing specificproposals to affiliate with other AHA councils, eg,Circulation and High Blood Pressure Research.

Since the Executive Committee of the Council onArteriosclerosis has approved a merger with the Councilon Thrombosis and since such a merger must precede atimely preparation of a joint proposal to the VascularBiology Working Group, l will call for a motion to mergethe two councils at the next meeting of our ExecutiveCommittee in November at Anaheim. Because of theimportance of this motion, l urge all present members ofthe Executive Committee to attend the meeting inNovember. Present plans are for our Executive Commit-tee to meet jointly with the Executive Committee of theArteriosclerosis Council at a luncheon meeting onSunday, November 12, and separately later that after-noon.

l apologize for the length of this letter, but l wantedyou to be fully informed of how we got to where we noware. Again, l invite your comments on issues related tothe proposed amalgamation with the Council on Arterio-sclerosis and the Vascular Biology Working Group. Youcan reach me äs follows:

Samuel l. Rapaport, MDUCSD Medical Center (8423)200 West Arbor DriveSan Diego, CA92103Telephone No: (619) 543-3552Fax No: (619) 543-3231e mail: SRAPAPORT@ucsd.edu

Invited Review

Resistance to Activated Protein C by Factor V Leiden: Clinical Implications

Until recently, no abnormality of hemostasis could befound in over 80% of patients with familial thrombophilia.The conditions detectable were primarily deficiencies ofprotein C, protein S, and antithrombin. Among allpatients with venous thrombosis these deficiencies arepresent in less than 5%.1i2This has changed dramati-cally with the reports on resistance to activated protein C(APC).

Protein C is a major natural inhibitor of coagulation. Itis activated by the negative feedback system of acti-vated thrombin and membrane-bound thrombomodulin.Activated protein C, when the coenzyme protein S ispresent, inhibits clotting by inactivating the procoagulantfactors Va and Villa. Addition of APC to plasma in vitrotherefore lengthens the clotting time.The first report onAPC resistance showed that some individuals withthrombophilia do not exhibit the expected Prolongation ofthe clotting time; ie, they are resistant to APC.3 It hasbeen shown that this resistance is the result of a muta-tion in the factor V gene (factor V Leiden), a single-baseSubstitution of adenine for guanine, corresponding to thecleavage site of protein C.4

Two tests are available to diagnose this abnormality, aclotting test for APC resistance and a DNA test (poly-merase chain reaction [PCR]) for the mutation. Theclotting test consists of performing two APTTs, onebefore and one after adding APC to the test plasma.The ratio of the two, preferably normalized to the APTTof normal pool plasma, is the APC-sensitivity ratio, whichis reduced in APC resistance. This clotting test cannotbe used for patients who are taking warfarin. The DNAtest is based on a PCR amplification, showing loss of anMnll restriction site at position 1691 when the Substitu-tion of adenine for guanine is present.

APC resistance increases the risk of venousthrombosis about eightfold and thereby is a risk factorfor thrombosis of similar strength äs protein C andantithrombin deficiency.5·6 The rare patient with homozy-gous factor V Leiden has a risk of thrombosis that isincreased up to 100-fold.7The risk in absolute terms ishighly dependent on age: in those under age 30, the riskfor a first thrombotic event is about 1 per 10,000 peryear for those without factor V Leiden and still only 6 per10,000 per year for heterozygous carriers. For thoseaged 50 and older, the risk is 2 per 10,000 per year forthose with the normal genotype and over 15 per 10,000per year for carriers of the mutation. For homozygouscarriers, the risk is one to several percentage points peryear.

There are other modifying factors besides age. First,risk estimates given apply to those without malignancy,

in which circumstance the risk may be higher. Second,oral contraceptives appear to increase the risk synergis-tically with factor V Leiden: for women aged 15 to 49who carried the mutation and used oral contraceptives,the risk of venous thrombosis is approximately 30 per10,000 per year, ie, at least a 30-fold increase.8 Theserisk estimates are based on studies conducted in theNetherlands, where there is an estimated overall risk offirst thrombosis of about 2 in 10,000 per year. Risk ofthrombosis with and without factor V Leiden may varybetween populations.

It is becoming more clear that the presence of severalrisk factors is needed to manifest thrombosis. This isillustrated by the reports in individuals with more thanone genetic defect, eg, protein C deficiency and APCresistance, in whom the risk of thrombosis is greatlyincreased.9These data may help to explain previouslyreported differences in clinical penetrance ofthrombophilic defects between and within families.10·11

Whereas it is ciear that factor V Leiden is the mostcommon determinant for deep-vein thrombosis, its rolein arterial thrombosis remains unclear. Some reportssuggest that it increases the risk of myocardial infarctionäs well äs ischemic stroke, whereas other studies foundno association.12'14 Although it may seem logical that arisk factor for deep-vein thrombosis would also increasethe risk of pulmonary embolism, no studies have specifi-cally examined this.

It is still unclear whether factor V Leiden is the etiologyfor all cases of hereditary APC resistance.15 If there arecases of APC resistance caused by other defects,however, these are very rare. Most discrepanciesbetween the clotting test and the DNA test appear toresult from laboratory problems with the clotting as-say.16·17 It therefore seems advisable to perform the DNAtest äs a first screen rather than the clotting test andcertainly not to base a diagnosis solely on the clottingtest.

The most remarkable feature of APC resistance byfactor V Leiden is its high prevalence. It is found in about50% of patients with familial thrombophilia, in 20% of allpatients with a first deep-vein thrombosis, and in 3% to5% of the general population.4~6This leads to much widerimplications than the rare deficiencies of protein C,protein S, and antithrombin because so many moreindividuals are affected.

Most importantly, in testing for factor V Leiden, there islittle reason to think in terms of "familial" thrombophilia.For deficiencies of protein C, protein S, and antithrom-bin, even if diagnostic tests are limited to those with aclear family history and no known explanation for the

thrombosis, the probability of a positive test is about10%. For APC resistance this probability is already twiceäs high if we would just test all patients with thrombosis.Indiscriminate screening of the total population wouldstill yield about a 5% incidence of carriers. Very fewwould advocate such a screening policy; still, the ex-ample forces us to reexamine the benefits of diagnostictesting.

Generally there are two possible benefits of a diagnos-tic test: first, the psychological benefit of knowing, andsecond, the medical benefit of subsequent preventiveinterventions.The former may differ from case to case;obviously, this is more important in families that havesuffered from unexplained thrombosis for many genera-tions. The benefit may be less obvious for a singlepatient with a first thrombosis, and the psychologicalbenefit may then reside mainly with the physician.

Because of the synergistic effect of APC resistanceand oral contraceptives, it is advisable to test for themutation before prescribing oral contraceptives inwomen with a suspected family history of thrombosisand in all women who experience venous thrombosiswhile using oral contraceptives. The decision of whetheror not to prescribe oral contraceptives in a carrier maybe difficult since all other reversible methods of contra-ception have a considerably higher risk of unwantedpregnancies (and subsequent postpartum thrombosis).

The benefit of preventive interventions is mainly toprescribe short-term anticoagulation in high-risk situa-tions (eg, surgery, plaster casts, immobilization, andpostpartum periods). Aspirin is not a proven therapy forvenous thrombosis prophylaxis. It seems reasonable tofollow the same clinical policy äs is done with deficien-cies of protein C and protein S. It is presently unclearwhether patients benefit from long-term therapy withwarfarin. This treatment does carry a well-documentedrisk of bleeding of about 3% per year even in dedicatedanticoagulation clinics,18 which is especially relevant inconsidering long-term prophylaxis.

Most centers would therefore not prescribe long-termanticoagulation after parturition in an asymptomaticpatient with a thrombophilic abnormality. Some wouldafter a first thrombotic event, and most would afterrecurrent events. There is less agreement on whether ornot to anticoagulate during pregnancy because of theneed for prolonged treatment with heparin and the risk ofbleeding, although the risk of thrombosis in pregnancy inthrombophilia is high.19 The high frequency of postpar-tum thrombosis, which can be prevented by a few weeksof anticoagulation, justifies short-term anticoagulationparturition.

Part of the expected benefits paradoxically depend onthe local anticoagulation policy in patients withoutthrombophilia: if this is extensive, äs in the Netherlands,where short-term anticoagulation is prescribed for allindividuals in most high-risk situations (except preg-

nancy and puerperium), there may be little preventivegain in diagnosing thrombophilia. If anticoagulation isless widespread, individuals may gain more from adiagnosis of thrombophilia and subsequent prophylaxiswhen indicated.

References

1. Heijboer H, Brandjes DPM, Büller HR, Sturk A, ten Cate JW.Deficiencies of coagulation-inhibiting and fibrinolytic proteins inoutpatients with deep-vein thrombosis. N Engl JMed. 1990;323:1512-1516.

2. KosterT, Rosendaal FR, Briet E, Van der Meer FJM, Colly LP,Trienekens PH, Poort SR, Vandenbroucke JR Protein C deficiencyin a controlled series of unselected outpatients: An infrequent butclear risk factor for venous thrombosis (Leiden ThrombophiliaStudy). Blood. 1995;85:2756-2761.

3. Dahlbäck B, Carlsson M, Svensson PJ. Familial thrombophiliadue to a previously unrecognized mechanism characterized by pooranticoagulant response to activated protein C: Prediction of acofactor to activated protein C. Proc NatlAcad Sei USA. 1993;90:1004-1008.

4. Bertina RM, Koeleman RPC, KosterT, Rosendaal FR, Dirven RJ,Ronde H de, Van der Velden PA, Reitsma PH. Mutation in bloodcoagulation factor V associated with resistance to activated proteinC.Nature. 1994;369:64-67.

5. KosterT, Rosendaal FR, Ronde H de, Briet E, Vandenbroucke JRBertina RM. Venous thrombosis due to poor anticoagulant responseto activated protein C: LeidenThrombophilia Study. Lancet.1993;342:1503-1506.

6. Svensson PJ, Dahlbäck B. Resistance to activated protein C äs abasis for venous thrombosis. N Engl JMed. 1994;330:517-522.

7. Rosendaal FR, KosterT, Vandenbroucke JR Reitsma PH. Highrisk of thrombosis in patients homozygous for factor V Leiden(activated protein C resistance). Blood. 1995;85:1504-1508.

8. Vandenbroucke JR KosterT, Briet E, Reitsma PH, Bertina RM,Rosendaal FR. Increased risk of venous thrombosis inoral-contraceptive users who are carriers of factor V Leidenmutation. Lancet. 1994:344:1453-1457.

9. Koeleman BPC, Reitsma PH, Allaart CF, Bertina RM.APC-resistance äs an additional risk factor for thrombosis in proteinC deficient families. Blood. 1994;84:1031-1035.

10. Miletich J, Sherman L, Broze G. Absence of thrombosis insubjects with heterozygous protein C deficiency. N EnglJMed.1987:317:991-996.

11. Bovill EG, Bauer KA, Dickermann JD, Callas R West B. Theclinical spectrum of heterozygous protein C deficiency in a largeNew England kindred. Blood. 1989;73:712-717.

12. Halbmayer W-M, Hanshofer A, Schön R, Fischer M.Theprevalence of pooranti-coagulant response to activated protein C(APC resistance) among patients suffering from stroke or venousthrombosis and among healthy subjects. Blood Coag Fibrinol.1994;5:51-57.

13. März W, Seydewitz H, Winkelmann B, Chen M, Nauck M, Witt l.Mutation in coagulation factor V associated with resistance toactivated protein C in patients with coronary artery disease. Lancet.1995:345:526-527.

14. Ridker PM, Hennekens CH, Lindpainter K, Stampfer MJ,Eisenberg PR, Miletich JP. Mutation in the gene coding for coagula-tion factor V and the risk of myocardial infarction, stroke, andvenous thrombosis in apparently healthy men. NEngl JMed.1995;332:912-917.

15. Zöller B, Svensson PJ, Xuhua H, Danlbäck B. Identification ofthe same factor V gene mutation in 47 out of 50 thrombosis-pronefamilies with inherited resistance to activated protein C. J ClinInvest. 1994:94:2521-2524.

16. Legnani C, Palareti G, Biagi R, Coccheri S. Activated protein Cresistance in deep-vein thrombosis. Lancet. 1994;343:452-542.

17. Rosendaal FR, Bertina RM, Reitsma PH. Evaluation of activatedprotein C resistance in stored plasma. Lancet. 1994;343:1289-1290.

18. van der Meer FJM, Rosendaal FR, Vandenbroucke JP, Briet E.Bleeding complications in oral anticoagulant therapy. Arch InternMed. 1993:153:1557-1562.

19. Conard J, Horellou MH, van Dreden P, LecompteT, Samama M.Thrombosis and pregnancy in congenital deficiencies in ATIII,protein C or protein S: Study of 78 women. Thromb Haemost.1990:63:319-320.

Dr Frits RosendaalDepartments of Clinical Epidemiology and Hematology

Leiden, The Netherlands

Committee and Liaison Reports

Report From the NHLBI

All divisions of the NHLBI—Blood (DBDR), Heart(DHVD), Lung (DLD), Epidemiology (DECA), andExtramural (DEA)—have moved to a new location inBethesda, Maryland. The Office of the Director, NHLBI,continues to be located in the main NIH campus. TheThrombosis and Hemostasis Scientific Research Grouphas a new telephone number, 301 -435-0070; fax num-ber, 301-480-1046; and mail stop code (MSC), 7950.

With the reorganization of the NHLBI, the DivisionAdvisory Committee has been replaced by the SpecialEmphasis Panel (SEP), which is convened äs needed.The Blood Division SEP met on April 27 and 28, 1995.The panel reviewed the old initiatives on hold äs well äsnew, timely ideas for possible implementation. Thefollowing is a partial list of ideas that were enthusiasti-cally recommended for further development. It wasrecognized that the budgetary environment may permitimplementation of only the top priority initiatives by theNHLBI.

• Genetic and other risk factors of thrombosis• Homing determinants in embryonic and hematopoietic

stem cells• Identification and characterization of human histocom-

patibility antigens• Immunogenetics of Inhibitor formation in hemophilia• Effects of sickle cell disease on the lung• Thrombopoietin, megakaryocytopoiesis, and platelet

production• New approaches to improve the function and viability

of platelets

The following are highlights of some of the fundingguidelines being followed at NHLBI at this time. Sincethese guidelines may change, investigators consideringsubmitting a research grant application are urged to callthe appropriate program Office for the latest Information.

Beginning fiscal year 1995, NHLBI has adopted amore flexible funding plan in that a small amount ofmoney is allocated to the divisions to fund applicationswith innovative ideas of high risk or potential clinicalimpact. Applications from young or minority investiga-tors will also receive consideration for support.

Competitive renewal applications are funded at nomore than 10% higher than the amount of direct costsawarded for the last year of the preceding project period.Investigators contemplating a significant expansion oftheir research program may consider submitting a newapplication. Competitive renewal of FIRST Awards to aregulär R01 grant is exempt from this budgetary restric-tion. Future year commitments is usually escalated at4% per year.

To achieve an overall average project period of 4years, NHLBI may reduce the duration of grants over acertain percentile by 1 year.

Program project grants are funded with a set-asidefund and do not compete with other regulär grants.However, these grants must meet the budgetary ceilingfor that year. Any investigator contemplating submittingan application for a program project grant should consultwith the appropriate program person äs soon äs pos-sible.

A variety of Information about NHLBI programs is nowavailable through the gopher on Internet atgopher.nhlbi.nih.gov.port:70. Although the gopher hasbeen in place only for short time, we are pleased to find

that it is being increasingly used by our Community.Please contact me at 301-435-0070 if you have anyquestions.

Pan Ganguly, PhD

Report From the Research Committee

The good news is that there has been an increase inthe number of funded national Grant-in-Aid applicationson a percentage basis for the AHA. This year, 185 outof 938 applications were approved forfunding at 19.7%.This percentage of funding was also achieved in thethrombosis study section; however, the numbers ofgrants received by the thrombosis Community this yearwas Iow. Only 40 grants were received compared with anormal year in which approximately 70 to 80 grants arereceived. l would encourage colleagues who are eligiblefor a Grant-in-Aid to compete for these awards.

At the last research committee meeting, March 31,1995, a number of alterations to existing national pro-grams and a new program called the "AHA ScientistDevelopment Grant" were approved. These changeswere approved by the Research Program and EvaulationCommittee and the Steering Committee.

A summary of these three proposed grant areas isprovided in the table beginning on page 8. The newAHA Scientist Development Grant is intended to supporthighly promising, beginning scientists in progress toward

independence by encouraging and adequately fundingresearch projects that can serve to bridge the gapbetween completion of research training and readinessfor successful competition äs an independent investiga-tor. The Scientist Development Grant will be supportedat the level of $65,000 per year with up to 4 years offunding. The Established Investigator Grant continuesbut has been increased in budget to $75,000 per yearand modified to include both salary and project support.The Grant-in-Aid award is also proposed to be altered toremove any restrictions from candidacy (such äs thoseimplemented in the past 2 years to limit access tobeginning investigators). The award value has beenincreased to $55,000. Note that renewals will not bepermitted; only newly initiated research projects will beconsidered for a Grant-in-Aid.

It is anticipated that these changes will take place inawards initiated in 1997 based on applications submittedin 1996.

Kenneth G. Mann, PhD

PROPOSED NATIONAL AHA RESEARCH PROGRAM PORTFOLIO

Summary of Award CharacteristicsApproved by Research Committee March 31,1995

Characteristics

ProgramObjective

ScienceFocus

Disciplines

Faculty RankMaximum

DegreeRequirement

ExperienceRestrictions

Citizenship

OtherRestrictions

Unique PeerReview Criteria

Common PeerReview Criteria

Pl Salary,Fringes Paid?

CommonBudget Items

AHA ScientistDevelopment Grant

To fund projects thatwill bridge the gapbetween researchtraining & readinessfor competition äsindependentinvestigator

El GrantTo support careerdevelopment of newlyindependentinvestigators byfunding projects forwhich support has notbeen obtained

Grant-in-AidTo fund distinct,highiy meritorious,innovative projectsfrom independentinvestigators

Research broadly related to CV function and disease, stroke, or torelated clinical, basic science, and public health problemsAll basic disciplines äs well äs epidemiological and clinicalinvestigations that bear on cardiovascular and stroke problemsAssistant Professor(or equivalent)

Associate Professor(or equivalent)

Professor(or equivalent)

MD, PhD, DO, or equivalent

No more than 4 yearselapsed since firstfaculty appointment

US citizen,permanent resident

Non-renewable.Awardees may applyfor El Grant in finalyear.Evidence that awardwill promoteindependence

At least 4 years butno more than 9 yearselapsed since firstfaculty appointmentUS citizen,permanent resident

Non-renewable.Prior Eis ineligible.Awardees may applyfor GIA in final year.Prior national-levelaward(s), evidence ofindependence frommentor

None

US citizen,exchange visitor,permanent residentAwardees mayreapply in final yearfor a different project.

Evidence of scientificindependence;innovative, distinctnature of proposal

Scientific merit of research proposal; qualifications, relevant experienceand productivity of applicant; relationship to Supervisor; adequacy ofavailable resources, facilitiesYes, consistent with% total effort, $ cap

Yes, consistent with% total effort, $ cap

No

Salaries of technical personnel essential to the project, supplies,equipment, travel, volunteer subject costs, publication costs, and 10%institutional indirect costs

8

CharacteristicsAnnual Award

PaymentComponents

Total AnnualAward Amount

AwardDurationMaximum

Total AwardCommitment

InterimReporting

Evaluation

AHA ScientistDevelopment Grant

Up to $30,000 forPl salary/fringes.At least $35,000 forproject.$65,000 including1 0% indirect costs

4 years

$260,000

El GrantUp to $35,000 forPl salary/fringes.At least $40,000 forproject.$75,000 including1 0% indirect costs

4 years

$300,000

Grant-in-AidUp to $50,000 forproject.

$55,000 including1 0% indirect costs

3 years

$165,000

Assessment of annual progress reports to include research findings,abstracts, publications and names of trainees supported (optional forScientist Development Grants)Publications, citations by others, ability to attract ongoing researchfunding, faculty advancement, other evidence of career progression,etc.

* Final decisions concerning award Characteristics will be madeby the Research Committee at its November meeting.

Progress Report on Arteriosclerosis, Thrombosis, and Vascular Biology

It is approximately 4.5 years since a separate editorialoffice for Thrombosis was established. During this time,the Journal has grown, expanding from a bimonthly to amonthly publication. Its scope has expanded äs well, äsreflected in the addition of the phrase "vascular biology"to the title.

The impact of the Journal continues to have a highranking according to the Institute for Scientific Informa-tion (ISI) measurements, and the Journal comparesfavorably with the top publications in the field of cardio-vascular biology and medicine. Among those Journalscategorized by the ISI under the rubric "cardiovascularSystem," Arteriosclerosis, Thrombosis, and VascularBiology was ranked fourth with an impact factor of 5.3 inthe latest Scientific Citation Index. What is of greatsignificance to the Council on Thrombosis is that ourJournal outranks those of its competitors that are specifi-cally directed to the field of thrombosis. For example, inthe 1993 rankings (the latest available), Thrombosis andHaemostasis ranked sixth and Thrombosis Researchranked 36th. The thrombosis portion of the Journalcontinues to develop and is attracting quality submis-sions. The number of thrombosis-related submissions tothe Vanderbilt editorial Office alone grew 25% in 1994,which followed 22% and 38% increases in 1993 and1992, respectively. Plans for the Journal currently beingimplemented include future publication of minireviews onfocused topics of current research.

We have been trying to improve the function of oureditorial Offices. Statistics for the Thrombosis editorialoffice show that 43.6% of 1994 manuscripts wereaccepted, 43.6% were rejected, and 12.7% remainunder revision. The interval from Submission of allmanuscripts to first decision was 6.9 weeks, while foraccepted papers, the interval from Submission to finaldecision was 21.0 weeks. The average priority rating formanuscripts ultimately accepted for publication was 2.7.

Examples of recently published thrombosis articles inArteriosclerosis, Thrombosis, and Vascular Biology arelisted below:

Platelet Biology• AM Vicari, ML Monzani, F Pellegatta, P Ronchi,

L Galli, F Folli. Platelet calcium homeostasis isabnormal in patients with severe arteriosclerosis(vol 14, no 9)

• PS Tsao, G Theilmeier, AH Singer, LLK Leung, JPCooke. L-Arginine attenuates platelet reactivity inhypercholesterolemic rabbits (vol 14, no 10)

• C Legrand, V Morandi, S Mendelovitz, H Shaked,JR Hartman, A Panet. Selective Inhibition of plateletmacroaggregate formation by a recombinant hep-arin-binding domain of human thrombospondin (vol14,no 11)

• J-C Ruf, J-L Berger, S Renaud. Platelet reboundeffect of alcohol withdrawal and wine drinking in rats:Relation to tannins and lipid peroxidation (vol 15, no1)

• A Notarbartolo, G Davl, M Averna, CM Barbagallo, AGanci, C Gianmarresi, FP La Placa, C Patrono.Inhibition of thromboxane biosynthesis and plateletfunction by simvastatin in type llahypercholesterolemia (vol 15, no 2)

• E Malle, A Ibovnik, HJ Leis, GM Kostner, PFJVerhallen, W Sattler. Lysine modification of LDL orlipoprotein(a) by 4-hydroxynonenal ormalondialdehyde decreases platelet serotoninsecretion without affecting platelet aggregability andeicosanoid formation (vol 15, no 3)

• H Ariyoshi, A Oda, EW Salzman. Participation ofcalpain in protein-tyrosine phosphorylation anddephosphorylation in human blood platelets (vol 15,no 4)

Vascular Biology• AM Schmidt, O Hori, J Brett, S Du Yan, J-L Wautier,

D Stern. Cellular receptors for advanced glycationend products: implications for induction of oxidantstress and cellular dysfunction in the pathogenesisof vascular lesions (vol 14, no 10)

• H-J Kruse, B Grünberg, W Siess, PC Weber.Formation of biologically active autacoids is regu-lated by calcium influx in endothelial cells (vol 14, no11)

• SL Diamond, F Sachs, WJ Sigurdson. Mechanicallyinduced calcium mobilization in cultured endothelialcells is dependent on actin and phospholipase (vol14,no 12)

• KB Lemström, PT Aho, CA Bruggeman, PJ Häyry.Cytomegalovirus infection enhances mRNA expres-sion in platelet-derived growth factor-BB and trans-forming growth factor-J, in rat aortic allografts:possible mechanism for cytomegalovirus-enhancedgraft arteriosclerosis (vol 14, no 12)

• PL Walpola, AI Gotlieb, MI Cybulsky, BL Langille.Expression of ICAM-1 and VCAM-1 and monocyteadherence in arteries exposed to altered shearstress (vol 15, no 1)

• F Mohamed, JC Monge, A Gordon, P Cernacek, DBlais, DJ Stewart. Lack of role for nitric oxide (NO)in the selective destabilization of endothelial NOsynthase mRNA by tumor necrosis factor-l (vol 15,no1)

• TW Wakefield, RM Strieter, CA Wilke, AM Kadell,SK Wrobleski, MD Burdick, R Schmidt, SL Kunkel,LJ Greenfield. Venous thrombosis-associatedinflammation and attenuation with neutralizingantibodies to cytokines and adhesion molecules (vol15,no 2)

10

• T Inaba, M Kawamura, T Gotoda, K Harada, MShimada, J-l Ohsuga, H Shimano, Υ Akanuma, ΥYazaki, N Yamada. Effects of platelet-derived growthfactor on the synthesis of lipoprotein lipase in humanmonocyte-derived macrophages (vol 15, no 4)

Pathways of Blood Coagulation• E Tremoli, S Eligini, S Colli, P Maderna P Rise, F

Pazzucconi, F Marangoni, CR Sirtori, C Galli. n-3fatty acid ethyl ester administration to healthysubjects and to hypertriglyceridemic patients re-duces tissue factor activity in adherent monocytes(vol 14, no10)

• RM Epand, A Stafford, B Leon, PE Lock, EM Tytler,JP Segrest, GM Anantharamaiah. HOL andapolipoprotein A-1 protect erythrocytes against thegeneration of procoagulant activity (vol 14, no 11)

• N Narahara, T Enden, M Wiiger, H Prydz. Polarexpression of tissue factor in human umbilical veinendothelial cells (vol 14, no 11)

• N Saha, Υ Liu, CK Heng, S Hong, PS Low, FSH Tay.Association of Factor VII genotype with plasmaFactor VII activity and antigen levels in healthyIndian adults and interaction with triglycerides(vol 14, no12)

• U Orvim, HE Roald, RW Stephens, N Roos,KJ Sakariassen. Tissue factor-induced coagulationtriggers platelet thrombus formation äs efficiently äsfibrillar collagen at arterial blood flow conditions(vol 14, no12)

• RM Barstad, MJAG Hamers, P Kierulf, Ä-B Westvik,KJ Sakariassen. Procoagulant human monocytesmediate tissue factor/Factor Vlla-dependent platelet-thrombus formation when exposed to flowingnonanticoagulated human blood (vol 15, no 1)

• BJ Warn-Cramer, Sl Rapaport. Evidence suggestiveof activation of the intrinsic pathway of blood coagu-lation after injection of Factor Xa/phospholipid intorabbits (vol 15, no 1)

• Sakata T, Kario K, Matsuo T, Katayama Y,Matsuyama T, Kato K, Miyata T. Suppression ofplasma-activated Factor VII levels by warfarintherapy (vol 15, no 2)

• T Kokawa, T Abumiya, T Kimura, M Harada-Shiba,H Koh, M Tsushima, A Yamamoto, H Kato. Tissuefactor pathway inhibitor activity in human plasma:measurement of lipoprotein-associated and freeforms in hyperlipidemia (vol 15, no 4)

Plasminogen Activator and PlasminogenActivator Inhibitor• HAR Stringer, P van Swieten, HFG Heijnen, JJ Sixma,

H Pannekoek. Plasminogen activator inhibitor-1released from activated platelets plays a key role inthrombolysis resistance: Studies with thrombigenerated in the Chandler loop (vol 14, no 9)

• T Padro, PHA Quax, CM van den Hoogen, P Roholl,JH Verheijen, JJ Emeis. Tissue-type plasminogenactivator and its inhibitor in rat aorta: effect ofendotoxin (vol 14, no 9)

• M Margaglione, G Di Minno, E Grandone,G Vecchione, E Celentano, G Cappucci, M Grilli,P Simone, S Panico, M Mancini. Abnormally highcirculation levels of tissue plasminogen activator andplasminogen activator inhibitor-1 in patients with ahistory of ischemic stroke (vol 14, no 11)

• LM Szymanski, RR Pate. Fibrinolytic responses tomoderate intensity exercise: comparison of physi-cally active and inactive men (vol 14, no 11)

• H Noda-Heiny, A Daugherty, BE Sobel. Augmentedurokinase receptor expression in atheroma (vol 15,no 1)

• X-N Li, VK Varma, JM Parks, RL Benza, JC Koons,JR Grammer, H Grenett, EM Tabengwa, FM Booyse.Thrombin decreases the urokinase receptor andsurface-localized fibrinolysis in cultured endothelialcells (vol 15, no 3)

Experimental Models of Thrombosis• A Gast, TB Tschopp, HR Baumgartner. Thrombin

plays a key role in late platelet thrombus growth and/or stability: effect of a specific thrombin inhibitor onthrombogenesis induced by aortic subendotheliumexposed to flowing rabbit blood (vol 14, no 9)

• RM Barstad, HE Roald, Υ Cui, VT Turitto,KJ Sakariassen. A perfusion chamber developed toinvestigate thrombus formation and shear profiles inflowing native human blood at the apex of well-defined stenoses (vol 14, no 12)

Prothrombotic Risk Factors• RS Rosenson, CG Tangney, JM Hafner.

Intraindividual variability of fibrinogen levels andcardiovascular risk profile (vol 14, no 12)

• J Emmerich, D Vidaud, M Alhenc-Gelas, G Chadeuf,M Gouault-Heilmann, M-F Aillaud, M Aiach.Threenovel mutations of antithrombin inducing high-molecular-mass compounds (vol 14, no 12)

• SE Humphries, S Ye, P Talmud, L Bara,L Wilhelmsen, L Tiret (European AtherosclerosisResearch Study group). European AtherosclerosisResearch Study: Genotype at the fibrinogen locus(G 455-A J-gene) is associated with differences inplasma fibrinogen levels in young men and womenfrom different regions in Europe: Evidence forgender-genotype-environment interaction(vol 15, no1)

• CA Spek, T Koster, FR Rosendaal, RM Bertina,PH Reitsma. Genotypic Variation in the promoterregion of the protein C gene is associated withplasma protein C levels and thrombotic risk(vol 15, no2)

11

New Antithrombotic Agents• J Strony, A Song, L Rusterholtz, B Adelman.

Aurintricarboxylic acid prevents acute rethrombosis ina canine model of arterial thrombosis (vol 15, no 3)

Jack J. Hawiger, MD, PhD

Agenda for Thrombosis Council Program at ASH Meeting

The program for the session to be jointly sponsored bythe Thrombosis Council of the American Heart Associa-tion and the American Hematology Society at this year'smeeting in Seattle is shown below. The Speakers willgive a 30-minute lecture that will be followed by aquestion-and-answer session on Saturday, December 2,beginning at 4:15. It will be cochaired by Sam Rapaportand Steve Prescott.

Staying in Control: Plasma Proteins That RegulateThrombosis and Inflammation

Platelet-Activating Factor Acetylhydrolase:An Anti-lnflammatory PhospholipaseStephen M. Prescott, MDUniversity of Utah

Plasma Proteins That Prevent Thrombosis: UnexpectedInteractionsJoseph P. Miletich, MD, PhDWashington University

Thermolabile Serpin Protease Inhibitor Mutants:Thrombotic and Inflammatory ConsequencesMark Wardell, PhDUniversity of Cambridge MRC Centre

Report From the Program Committee

Dr Prescott reported that the Program Committee willmeet in Fall 1995 to begin planning the NationalThrombosis Conference to be held in conjunction withthe 1996 Scientific Sessions of the AHA. He encouragedthe committee members to submit suggestions forprogram topics and Speakers.

He also reported that the number of evening sessionswill be decreased and the selection of Speakers will becoordinated to eliminate overlap. It was moved,seconded, and carried to continue to Sponsor Sundayafternoon programs on topics attractive to broadercommunities.

Stephen M. Prescott, MD

Budget Report

Dr Rapaport reported that the Council will have $19,060in new discretionary funds for fiscal year 1995-1996 plusany unexpended funds from fiscal year 1994-1995. Itwas moved, seconded, and carried to approve thediscretionary budget for fiscal year 1995-1996:

Membership recruitmentNewsletterIntercouncil working groupsYoung Investigator PrizesThrombosis travel stipends

$2,000.004,000.001,500.00

N/AN/A

Arteriosclerosis/Thrombosis/Vascular Biology Conference 5,000.00

Gordon Conf. on Hemostasis 4,000.00Integration Initiative 1.000.00Total $17,500.00

It was moved, seconded, and carried to defer increasingthe monetary award for the Thrombosis Young Investiga-tor Prize until a final decision and details of amalgam-ation with the Council on Arteriosclerosis and the Work-ing Group on Vascular Biology are made.

Samuel I. Rapaport, MD

12

Annoimcements

Joint Conference on Arteriosclerosis/Thrombosis/Vascular BiologyFebruary 18-20, 1996. Salt Lake City, Utah.Sponsored by the Councils on Arteriosclerosis andThrombosis and the Intercouncil Working Group onVascular Biology.

This Conference will bring together scientists fromatherosclerosis, thrombosis, and vascular biology todiscuss the interrelationships of their areas of researchand to provide Information on the latest advances inthese areas. Emphasis will be given to modern tech-nologies involving molecular genetics.

Abstracts for this Conference are due Friday,November 17,1995. For more Information, call 214-706-1100, fax 214-373-3406, or write to the AmericanHeart Association, Scientific and Corporate Meetings,7272 Greenville Avenue, Dallas, TX 75231-4596.

TRIGGER: An Electronic Newsletterfor Researchers Working on theBiology of Tissue Factor and FactorVII

An electronic newsletter has been started to facilitatecommunication among researchers working on thebiology of the triggering complex of the blood clottingSystem (tissue factor and factor VII). TRIGGER willcarry titles and brief descriptions (or abstracts) of papersrecently accepted for publication, meeting announce-ments and reports, positions available, technical ques-tions, etc. The newsletter will be sent via e-mail.

For more Information (including how to subscribe),send a message with your preferred e-mail address totrigger@omrf.uokhsc.edu. Information can also beobtained via the World Wide Web at http://omrf.uokhsc.edu/~trigger/or by contacting either JamesH. Morrissey (morrisseyj@omrf.uokhsc.edu) or Pierre F.Neuenschwander (pierren@omrf.uokhsc.edu) at theOklahoma Medical Research Foundation, 825 NE 13thStreet, Oklahoma City, OK 73104. Tel 405-271-7892.Fax 405-271-3137.

13

Application forMembership

Council onThrombosisCouncil dues are $25/year

The purpose of the council is to achieve theobjectives of the AHA in the field of thrombosis,specifically äs they relate to research, Professionaleducation, and the application of these matters toclinical science. A chief objective is to viewthrombosis in all its ramifications, rather than solelythrough its effect on the heart, brain, and kidney.

The council conducts postgraduale seminarsand scientific sessions, either separately or in coop-eration with other scientific councils. It also assists indevelopment of educational materials, evaluatesmedical Knowledge with respect to its application incontrolling thrombosis, and collaborates with othercouncils in areas of mutual concern and interest.

Council members represent a large number ofdisciplines, enabling a forum for eventual Solutions tothe problems of thrombosis at all levels—basicresearch, clinical investigation, community healthProblems, and public understanding.

This offer expires December 31, 1995

Please mail completed form along with payment to:

American Heart AssociationScientific Publishing

PO Box 843543Dallas, TX 75284-3543

OR

fax credit card Orders to214-691-6342

Questions?Call 214-706-1310 or 214-706-1201

Please share this with interested colleagues

5NEWS1/2

Name

JYES! l want to join the Council on Thrombosis.

Address_

City/State/Postal Code_

Country

Telephone_ .Fax.

E-Mail Address

Month and Year of Birth

Race/Ethnicity:

D American Indian

D Asian

D Black

D Hispanic

O White

/ Gender:

% of time spent (=1 00%):

Administrative

Patient Gare

Research

Teaching

Other (specify)

D M D F

Are you interested in Vascular Biology? D Yes D No

Specialty

JYES! As an AHA Council Member, l want tosubscribe at these special prices.

United States Outside USNon- Non-

Member Member Member MemberD Arteriosclerosis, Thrombosis,

and Vascular Biology $109 .... $146 $145 $182G Cardiovascular Nursing 6 6 15 15D Circulation 101 135 203 237D Circulation Research 128 171 194 237D Currents in Emergency Cardiac Care... 12 12 16 16Π Hypertension 101 135 141 175D Stroke 101 135 155 189

Please Start my subscription with the. issue

ADVANCE PAYMENT REQUIRED

D Check or money order enclosed (payable to the American HeartAssociation drawn on US bank in US dollars)

D MasterCard

Card Number

D Visa D American Express

Expirationdate.

Signatare äs it appears on card:

Total payment $_

14

AHA Services

Το provide you with the bestcustomer Service, listed below are theServices and contact numbers you aremost likely to need.

To ensure timely delivery of yournewsletter, Journals, and other impor-tant Information, please send us youraddress changes and phone and faxnumbers using the coupon below.

AHA National Center7272 Greenville AvenueDallas,TX75231-4596

Tel 214-373-6300 Fax 214-691-6342gopher.amhrt.org

Service

Address Changes

AwardsCouncil New Investigator AwardResearch AwardStudent Scholarship (Council)

ConferencesAnnual Scientific SessionsScientific Conferences

Council MembershipApplications — CatalogBilling Information

Donations/Memorials

JournalsAdvertisingBilling InformationPermissionsReprintsSubscriptions — Catalog

PublicationsPublic/Patient EducationScientific Statements

Department

Customer Service

MeetingsResearch AdministrationScientific Councils

MeetingsMeetings

Customer ServiceCustomer Service

Finance

Scientific PublishingCustomer ServiceScientific PublishingScientific PublishingCustomer Service

Local AHA OfficesInquiries

Telephone

214-706-1310 or 1201

214-706-1685214-706-1453214-706-1476 or 1261

214-706-1253214-706-1511 or 1414

214-706-1201214-706-1310 or 1201

214-706-1417

214-706-1426214-706-1310214-706-1309 or 1313214-706-1466214-706-1310

800-242-8721214-706-1220

Fax

214-691-6342

214-373-3406214-706-1341214-373-0268

214-373-3406214-373-3406

214-691-6342214-691-6342

214-368-1228

214-691-6342214-691-6342214-691-6342214-691-6342214-691-6342

214-706-1341

E-Mail

pubcust@amhrt.org

daphner® amhrt.org

pubcust@amhrt.orgpubcust@amhrt.org

pubcust@amhrt.orgpubauth@amhrt.orgpubauth@amhrt.orgpubcust@amhrt.org

MOVING?Please print your new address below:

Name

Address

City State/Province/Country Zip/Post Code

Phone Fax

E-mail

Moving date

IMPORTANT!

ATTACH ADDRESS LABEL HERE

Clip this form including your mailing label and send to:AMERICAN HEART ASSOCIATIONScientific Publishing7272 Greenville AveDallas, TX 75231-4596Fax 214-691-6342Tel 214-706-1310

1

American HeartAssociation Jl-!'jh!:ng Henri Discnse

find StmKa

You'd use it in anemergency.

Why not use itto prevent one?Some people in Washington want to slashgovcrnment funding for biomedical rcscarch.We're fighting tbr rescarch, but we nced your help.If you won't lift a finger for research, how can youexpect anyone eise to?WhiteHouseCommentLine: (202)456-1111-CapitolSwitchboard: (202)224-3121-PresidentClinton'se-mail: prcsident@whitehouse.gov

Research Funding. Talk it up.