Bedreaga, Minodora

Blendea, Dan

Crisan, Sorin

Duncea, Caius

Zarich, Stuart

Elsevier - Publisher Connector 

Changes in left ventricular structure and function predict the onset of hypertension in adult normotensives with a family history of hypertensive disease: A seven-year follow-up study 

276A ABSTRACTS - Vascular Disease, Hypertension, and Prevention JACC March 19,2003 
Conclusions: A regular dose of C increases WR. A second dose consumed shortly after 
produces a smaller but discernible adverse effect on WR adding up to a prolonged total 
effect. This finding has impoltant implications for arterial stiffening and the pulsatile load 
of the heart and may be involved in the pathogenesis of hypertension. 
1133-118 Changes in Lefl Ventricular Structure and Function 
Predict the Onset of Hypertension in Adult 
Normotensives With a Family History of Hypertensive 
Disease: A Seven-Year Follow-Up Study 
Dan Blendea Caius Duncea, Stuarl &rich. Sorin Crisan, Minodora Bedreaga. Roman 
Vlaicu. University of Medicine and Pharmacy, Cluj-Napoca, Romania, Bridgeport 
Hospital, Bridgeport. CT 
Background: Alterations in left ventricular (LV) structure and function have been previ- 
ously shown in normotensive offspring of hypertensive (HT) families but their significance 
is still unclear. 
Methods: To verify if these alterations have predictive value for the onset of HT disease, 
205 norrnotensive adults (mean age 43+/-10 yrs) with family history of HT. were exam- 
ined echocardiographically (2D, M mode, Doppler) at baseline and then repeatedly at 12 
months intewals, during a follow-up period of 7.1 yrs (range 4-7.5 yrs). 
Results: During this period, 57 subjects (26%) became hypertensive (H group). These 
subjects had higher values for the baseline LV mass index (LVMl)(97 +/- 25 g/m2 YS 81 
+/- 21 g/m2: p<O.Ol), lower age adjusted E/A ratios (1.1 +/- 0.4 vs 1.4 +/- 0.4; p<O.OOl). 
and lower LV longitudinal fractional shortening (0.16 +/- 0.03 vs 0.19 +/- 0.03; p=O.O36) 
compared to those who did not develop HT (N group). The subjects in the H group had 
also higher initial systolic blood pressure (SBP) (134 +/- 12 mmHg vs 117 +/- 11 mmHg; 
pcO.01) and a higher number of 1 st degree relatives with HT (2.9 +/- 0.3 vs 1.5 +I- 0.4 ; 
p= 0.044). 
There was no significant difference in baseline LVEF, LV clrcumferentlal fractIonal short- 
ening, LV and diastolic diameter and left atrial size between H and N subjects at base- 
line. 
SBP at the end of the follow-up was predicted independently by the initial SBP 
(beta=0.359; pcO.Ol), age (beta 0.01, p=O.O42) and LVMI (beta=0.165; p<O.Ol). 
During the follow-up period, the subjects who subsequently developed HTN. experienced 
a significant increase in LVMI (from 97+/-25 g/m2 to 104 +/- 26 g/m2; p=O.O39), and 
increase in aortic diameter (from 32 +/- 4 mm to 36 +I- 6 mm; pcO.01). The paired differ- 
ences for all these parameters were significantly higher in the H group compared to the N 
group. H subjects had also higher variations in LV-E/A between the echo exams in the 
follow-up period when compared to the N group (coeff var 25% vs 12%; pcO.01). 
Conclusions: Increased LV mass and alterations in LV diastolic and systolic longitudinal 
function predict the onset of HT in normotensives with family history of HT. Increased 
variability in LV diastolic function seem to appear during the period of developing HT. 
1133-119 N-Terminal Pro-Brain Natriuretic Peptide Predicts 
Cardiovascular Events in Hypertension: A LIFE 
Substudy 
Michael H. Olsen, Kristian Wachtell, Christian Tuxen, Eigil Fossum. Lia E. Bang, 
Christian Hall. Hans Ibsen. Jens Rokkedal. Richard B. Devereux. Per Hildebrandt 
Glostrup University Hospital, Copenhagen, Denmark, Frederiksberg University Hospital, 
Copenhagen, Denmark 
Background: N-terminal pro brain natriuretic peptide (NT-proBNP) is a strong cardio- 
vascular risk factor in patients with chronic heart failure as well as in the general popula- 
tion. We wanted to investigate whether high NT-proBNP could predict the composite 
endpoint (CEP) of cardiovascular death, non-fatal stroke or non-fatal myocardial infarc- 
tion in patients with hypertension and left ventricular hyperlrophy as well. Methods: After 
two weeks of placebo treatment and yearly for 4-5 years clinical, laboratory, and 
echocardiographic variables were assessed in 164 hypertensive patients from the LIFE 
Echo substudy, aged 55-60 (mean 66~7) years. with electrocardiographic LV hypettro- 
phy. NT-proBNP was measured by immunoassay (Elecsys proBNP) at baseline and after 
one year of treatment. 
Results: CEP occurred in 25 patients. Baseline NT-proBNP above the median value of 
165 pg/ml was associated with higher incidence of CEP (16.7% vs 6.7%, P<O.O5). 
Known cardiovascular disease (n=60) defined as diabetes (n=20), or history of either 
ischemic heart disease (n=26), cerebrovascular disease (n=l9), peripheral vascular dis- 
ease (n=5) or chronic heart failure (n=2). was also associated with higher incidence of 
CEP (24.6% vs. 8.9%, P<O.Ol). NT-proBNP above the median value was not associated 
with higher incidence of CEP in this high-risk group (24.3% vs. 21.7%, NS), but was in 
the remaining 124 “low-risk” hypertensive patients (14.6% vs. 4.3%, kO.01). In Cox 
regression analyses controlling for treatment assignment NT-proBNP (PcO.05) predicted 
CEP slightly more strongly than prior cardiovascular disease (kO.054) and current/prior 
smoking (P=O.O6). Systolic blood pressure, gender and body mass index did not enter 
the model. NT-proBNP levels after one year of treatment also tended to predict the CEPs 
that occurred subsequently (18.6% vs. 9.2%, P=O.O7). Conclusion: NT-proBNP is a 
Strong cardiovascular risk factor in patients with hypwtension and LV hypemophy, espe- 
cially in the group without diabetes or clinically overt cardiovascular disease. Further- 
more, our data suggest the possible use of NT-proBNP - even measured dunng 
treatment. as a practical tool for risk stratification in hypertension. 
1133-146 Genetic Analysis of Multiple Risk Factor Syndrome in 
Rats 
Takehiro Watanabe, Yi-Qiang Liang. Hyoe Inomata, Kazuyuki Yanai, Yoko lizuka, 
Takanari Gotoda, Norihiro Kate, International Medical Center of Japan, Tokyo, Japan, 
Tokyo University, Tokyo, Japan 
Background: According to epidemiological studies, cardiovascular risk factors tend to 
cluster in certain individuals, which has been widely recognized as the multiple risk factor 
syndrome. To clarity pathophyslological mechanisms underlying the multiple risk factor 
syndrome, we performed extensive genetic analysis using a unique model organism, the 
spontaneously hypertensive rat (SHR). 
Methods: We undertook genome-wide screens in 2 F2 cohorts independently produced 
from the Wistar-Kyoto rat and SHR of a Japanese colony (151 males in F2-1 and 175 
males in F2-2). In addition to blood pressure. plasma lipid, glucose and insulin levels, 
and body weight, in vitro phenotypes associated with insulin resistance and fat pad 
weight were evaluated in F2-1, while part of F2-2 (n=32) were fed high-fat-high-choles- 
terol (HFHC) diet between 15 and 17 weeks of age. 
Results: In the entire progeny, the most significant linkage to blood pressure was found 
near D3Mitl4 on rat chromosome 3 (maximal LOD score=5.0), where linkage to triglycer- 
ide levels was concomitantly observed. Also, suggestive linkage was observed for blood 
pressure and cholesterol levels on rat chromosome 19. Significant linkage to body weight 
was observed near DZMit5 on rat chromosome 2 (maximal LOD score=4.0 in FZ-2). 
There was a suggestive evidence of linkage to in vitro phenotypes, i.e., glucose uptake 
and lipolysis measured in isolated adipocytes, in a region between D4Mghl7 and 
D4Mghll on rat chromosome 4. far distant from the Cd36 locus. In several chromosomal 
regions, statistical significance of lknkage was enhanced after HFHC diet. 
Conclusion: We have identified the clustering of linkages to more than 1 phenotypic traits 
on a few chromosomes, suggesting the potential existence of genes controllmg multiple 
cardiovascular risk factors at least in rats. Our data also provide a substantial evidence 
for a gene-environment interaction, that is, some quantitative trait loci become prominent 
after a certain dietary intewention. Further investigation including the development of 
congenic strains is currently in progress to resolve these issues. 
1133-147 Cardiovascular Morbidity and Mortality in Hypertensive 
Patients With Atrial Fibrillation: The LIFE Study 
Kristian Wachtell. Bjijrn Horn&am, Mika Lehto, David J. Slotweiner, Eva Gerdts, Peter 
Aurup, Bjijrn DahlW, Hans Ibsen, Steve Julius, Sverre E. Kjeldsen. Markku S. Niemlnen, 
Jens E. Rokkedal, Richard 8. Devereux, Glostrup University Hospital, Glostrup, 
Denmark, The Weill Medical College of Cornell University, New York, NY 
Background: OptImaI treatment of hypertensive patients with atrial fibrillation (AF) to 
reduce the risk of cardiovascular morbidity and mortality remains unclear. 
Methods: As part of the LIFE study, 324 patients (42% women) with AF and hyperten- 
sion (mean age 70+6, pressure 176+14196+10 mmHg) and electrocardiographic left ven- 
tricular (LV) hypertrophy, were assigned to losartan- or atenolol-based therapy for 1,365 
patient-years of follow-up. 
Results: The primary composite endpoint occurred in 36 patients in the losartan-group 
(n=l50) vs. 64 in the atenolol-group (wl74); relative risk (RR) 0.60 [95% Cl 0.40.0.921. 
P=O.O18. Cardiovascular deaths occurred I” 20 vs. 37 patients in the losartan- and 
atenolol-group, respectively: RR 0.58 [Cl 0.34-I ,011, P=O.O53. Stroke occurred in 16 vs. 
37 patients (RR 0.56 [Cl 0.31.0.971, P=O.O40), and myocardlal infarction in 11 vs. 7 
patients (P=NS). There was a trend towards lower all-cause mortality; 30 vs. 46 (RR 0.67 
[Cl 0.43.1.071, P=O.O92), and hospitalization for heart failure took place in 15 vs. 23 
patients (P=NS). Adjustment for blood pressure levels during follow-up had little impact 
on cardiovascular benefit of losartan. 
Conclusion: Los&an was more effective than atenolol-based therapy in reducing the 
risk of the primary composite endpoint of cardiovascular morbidity and mortality as well 
as the secondary endpoints of stroke and cardiovascular death, I” hypertensive patients 
with electrocardiographic LV hypertrophy and AF and there was a trend towards lower 
ail-cause mortality. Hypertensive patients with electrocardiographic LV hypertrophy and 
AF seem to benefit more, for the same blood pressure lowering, from losartan than from 
conventional antihypertensive and antiarrhyihmic treatment by atenolol. 
1133-148 Cardiovascular Safety of Vardenafil in Patients 
Receiving Antihypertensive Medications: A Post-Hoc 
Analysis of Five Placebo-Controlled Clinical Trials 
Robert A. Kloner, Puneet Mohan, Thomas Segerson, Marc Thibonnier, Christ&w 
Norenbarg, Harin Padma-Nathan, Good Samaritan Hospital, Los Angeles, CA, The Male 
Clinic, Beverly Hills, CA 
Background: Hypertension is associated with erectile dysfunction (ED). Phosphodi- 
esterase-5 (PDEd) inhibitors may potent&e blood pressure (BP) reduction of antihyper- 
tensive agents (HTM). This study evaluated the cardiovascular safety of vardenafil, a 
potent, selective PDE-5 inhibitor when used with HTM. 
Methods: Data ware extracted from 5 double-blind Phase Ill trials in which 2,716 men 
with ED received vardenafil 5, 10, or 20 mg or placebo as needed for up to 26 weeks. 
Adverse events and vital signs were tabulated at all visits; in a patient subgroup (n=703), 
vital signs were recorded 11 min to 5 h post-dose. Vardenafil doses were pooled and 
analyzed by HTM use. 
Results: In 2,605 patients valid for safety (vardenafil-1,812, placebo-793), 21 HTM was 


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Changes in left ventricular structure and function predict the onset of hypertension in adult normotensives with a family history of hypertensive disease: A seven-year follow-up study

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