D22 Gender differences in insulin sensitivity and sympathetic responsiveness in young hypertensives

11OA

A]H-APJUL1997-VOL. 10, NO. 4, PART 2

ASH XII ABSTRACTS

D20 EFFICACYOF A LOW DOSE NIFEDIP3NBGfTS (20 MG) fN PATIENTSWTI’HMILDTOMODERATEHYPERTENSION C& mfcrtbc CanadianInvesfigatora.Beyerhrc.Etobicokc,Ontario. of Nifbdipiac GITS (N-GITS) is a ence a day fcrmmdation nitkdipinepmvidhg atabkplasmaconwnfmfiona overthcentirc24 heurdoaingirrtaval. To assesstbesndbypema ive efficacyofarrew 20mg fomtrrfation in anofficebased setting, M centreaacmssthc Countrvand lg7 Dstierrtswere-ted. A&r a twe week lrlscebe ofpidor N-GITStreatment blcad prCS!OXt monitoring cccurreelin a subgroupof 66 pSti611tS at 5 of tbc cadres. A SIOIUUZUY of the “intentic+rt etreat” resultsis * below: S doubi-blind

manner t04”&dra

24 hour smbukry

A DBP (errnrHg)

-5.4

-8.6@

SBP(rmrrHg)

.5.0

-9.3.

A

Rc3pondms’(%)

31,9

T/Pratio(DBP) 37,2Y. AdVerw Ev da DBP < 90mrrWg IX> 10 rmnHgrtecreaae; p=o.ool; *p=o.oo63

1

Metoprelel euccinate extended release (ER) tebleta ere formulated te provide a controlled end predictable releaaa of metoprolol for 24 heutsallevhrgfe reneedaily administration. The efricacyand safety of metoprelol ER were compered to immadiate releasa (IR) metepmlel tattrate in a randomized,deubie-L4ind,placebe-controlled, parallelgreup, multicenter study in patients with mild to mederate hypertarrehr. Aftara single-blind placebo run-in period, 198 patients with a diasfelic blood pressure (BP) of 95-110 mmHg were randomized to receive placebe, 50 mg metoprolol ER, or 100 mg metoprelol IR omcedaiiyfor 8 weeks. Results efthe primary efficacy variable, mean change from beseline in seated cuff BP measured in the ChdC 24-houre postdose, are summarized belew: Sasdlne BP(rmnHg)

Aweak4 (m)

w

=W

15211C0 -10.6../-9 .4.-.

ICOmg Matnpfo!al IR(n=63)

lslilml

PlacekI(n=S6)

13311W

A Week S W

(mnlf9) -9.3../-6.1..

MefoprololER(n=&)

66.7% (

Tksertaultsirr&atethet20mgofN-GITSis enefflcacioua dosein rk?messirrgBPwiflr alewineidenceofedveraemwrrta.

Key Words:

OF THE ONCE-DAJLY ADMfNISTRAllON OF 80MG EXTENDEORELEASE ANO1OO MG IMMEOIATE RELEASE METOPROLOL TABLETS IN PATfENTS WITH MILO TO MODERATE HYPERTENSION W, Friahman“, Afbert Einstein College of fdedicine,Brenx,NY, L. P. Haskell”, G. Frfdey, Asffe USA, Inc.,Waetboro, MA and M.A. Weber, Brookdele Hespital, Srooklyn, NY for the Toprel-XL Study Greup

Treatment

57,0

32.3°. /

D21 ACOMPARISON

NifedipinaGITS,T/P,Hypcrtemion

-6.2./-.35.”” -6.4./.9.2.. -3.64.5

.2.44.4

.Ps .WJ.versus@acebO; “.Ps .010,vsrsusp4amb0;..*P ..03! F48cebo.DifferenwsbetweenmetcprddERsrd rnctcpreldIRH nd statistkaliysignificant(p >.050). The inctience ef adverse events was similar between treetmenta. Thus, half the daily dose of metoprelol ER resufted in clinically equivalent decreases in trough clinic BP when compared te metoprolol IR.

Ke#Wor~: a hype ensive, metoprolol, beta-blecker

D22

D23

GENDER DIFFERENCES IN INSULIN AND SYMPATHETIC SENSITIVITY

SERUM LIPOPROTEIN(a) [LP(a)] LEVELS AND APOLIPOPROTEIN(a) ISOFORMSIN HYPERTENSIVEPATIENTSWITH AND WITHOUT RENAL FAILURE:EFFECTSOF AN71HYPERTENSIVETREATMENT. LA .%ehi”, F Kronenkerg, L Zingaro, S De CarIi, C Catena, E Falletl, E Bartoli. Hypertension Unit, Oepsrfrnent of Internal Medicine, Univerwfy of Udine, Italy and Institute of Medical Biology and Human Gerrefbs, University of Innsbruck, Austria. Lp(a) k a MSjOr hrdepmdent risk facter for atherasckroais and e powerful predictor of the presencs of terget+rgen damage in hypertensive patients (Sechi et al., Am J Hypertens, 1994). Increasad levels et Lp(a) have been found in pstierdswifh end-stage renal disease and can acwunt for the increased cardiovascular risk demonstrated in these patients. In this study w hava evaluated the serum levels of l-p(a), ap@ip3proteirw, and aPO(a) iSOfOrMSm 365 subjects with mild-mederste essenfiil hypwtension: 224 subjects (age: 52*14 yr) had nerrrml renal function (HT) and 141 subje@e(age: 5%13 yr) had impaired renal function (PCrea>l.2 mg/dl and/or Crsat Ckara rwe@Oml/min/l.73 mq) (RF). Subjects with obesity (BMIx30), diabetes, familial hypercholestero!emis, ard advanced renal failure (PCreab2.5 mg/dl and/or Crest Clesra~30ml/rtrin/l .73 mq) were excluded The hypertensive sub@cfe sere mmpered with 102 nonrmtensive subjects (NT), matched for age, sex, and BMI, Serum Q(a) levels were measured bya double-antibody ELlSA and spa(a) isoforrns by immututblofting. The serum Lp(a) levels and the frequency distribution of ape(a) isotorms were comparable in hypertensive and NT subjects. Pfasma triglycerides, total-, LDL-, snd HDL-eholeeterol and afmlipeproteins (Al, All, B, Cll, CIH, E) Ievals wre eempsrabke in HT and RFsubj-de. Lp(a) tevels wre significsntfy greater in RF (median 12.9 mg/dl) than HT (7.9 nrg/dl), but ffra frequemcydistributkm of LMWap@a) QQ&2! UAltr !-P(a) A!T 11043 16.649.4 hT llr3Q4 21#24 14.1*16.6 26.7?A w 66*16’ 55*153’ 22.7*24.8” 30.0% did rot d~er bsfwaan these groups, indicating that the increase in Lp(a) ia not genetically determined and is a likely consequenea of decreeeed renel catabolism of this lipoprotein. In a separate study, 40 essential hypertensive subjects with impaired renal function wre randomly assignedto antihypertensivetreatmentwitheither amk%tipine,10 rr?gq.d. @=~), or ena@W .20 mg q.d. (n=20). After one year, bothtreatments decrsasad signflicentlysystolicsnd diastolicbleed pressurebut no ettwt was observedon serum Q(a) mnmntratiens (amlodipine:medisn frem 12.0 to 11.6 m?jdl;enalapril: rrredianfrom 12.6 to 12.3 rn@dl). Thus, ihcreesedLp(a) levelscan cenfributeto an i_weaead cerdWascukar risk i~ h~deneive PSfienfS~h mikiirrpeirmenfof renal fu~ion. Tr~fmenf WffI am!cdpine or enelapnl doea net affect serum Lp(a) Ievek. Iipopretein(a), Spolipcqrroteine,amlodipir+e,enalapril Kay words:

RESPONSIVENESS IN YOUNG HYPERTENSIVES K. Masuo*zH. Mikami*, T. Ogihara*.Dept. of GeriaticMed. OsakaUniversityMedicalSchool,Osaka,Japan. To evaluatethe genderdifferencesin ameliorativeeffectson insulin(INS)sensitivityand sympatheticresponsivenessduring 5-yr treatment with captopril(C) or nifedipine-retard(N) in young, non-obese hypertensives(HT).26 normotensive men with C, 38 (NTM), 13NT women (NTF), 81 HTM treated HTF treated with C, 78 HTM treated with N, and 44 HTF treated with N were measured hlood glucose, plasma insulin(lNS),norepinephrine(NE)every 30min for 2 hrs after 75g oral glucose ingestion every year for 5 yrs. Six groups were matchedin age and BMI(41Myrs, 23.0+1.3 kg/m2). BP reduction after Tx were similar to each other among 4 HT groups during 5 yrs. At entry period, AUC of BG, AUC of INS,AUC of NE in HT were significantlygreaterthan those in NT (P<.05, P<.01, Pc.01). Although there were no gender differences in AUC of BG and AUC of INS, AUC of NE in HTF were significantly greater than in HTM(P<.05) at entry period. AUCof INS decreasedsignificantlyafter l-yr Tx with C in HTM,after2-yrTx with C in HTF, after I-yr Tx with N in HTM and after 2-yr Tx with N in HTF. In HTF and HTM treated with C, AUC of NE decreased after Tx, on the other hand, in HT treated with N regardlessof gender,AUC of NE increased. Ratio of %AINS (max INS-basal INS/basal INS) increasedsignificantlyin both HTF and HTM regardless of kinds of Tx. Ratioof %ANE in both gender HT treated with C increased significantly at 2-yr Tx(F:P<.05, M: P<.05), while the ratio in HTF and HTM treated with N decreased at 5yr(P<.05) and 3-yr of Tx (P< .05). These results demonstrate

that reduced INS sensitivity and responsiveness exist in HT regardless of gender. ACE-1 and Ca channel blocker have ameliorativeeffectson INS sensitivity & [“NSresponsiveness in HT. but those effects are stronger in men than women. ACEU@@?4cvdaom calcium blocker in effect on responsiveness of sympathetic activity. insulin, norepinephrine, ACE-inhibitor, Calcium channel blocker