Transcript Patient and methods

Cardiovascular Risk Factors in Patients with
Uncontrolled and Long-Term Acromegaly:
Comparison with Matched Data from
the General Population and the Effect of
Disease Control
J. Clin. Endocrinol. Metab. 2010 95:3648-3656
originally published online May 12, 2010
R1 Hyun Jun Joung/Pf. Sung Woon Kim
Introduction


Acromegaly
 chronic GH and IGF-I excess status
 increased morbidity and Mortality d/t cardiovascular, cerebrovascular
disease
 aggravated by comorbidities like obesity, hypertension, impaired glucose
homeostasis, or dyslipidemia
unclear whether and to what extent acromegalic patients are at risk for CHD
 So far, the existing data : mainly refer to heterogeneous cohorts and to
pathological examination of old series of patients
 Recently, CHDrisk in patients with acromegaly was evaluated through the
calculation of the FRS(Framingham risk score)
 FRS : based on the analysis of conventional risk factors (sex, age, left
ventricular mass, HTN, smoking habit, DM, and lipid status)

The aim of the study
 to evaluate the prevalence of cardiovascular risk factors and the FRS in
patients with active acromegaly
 to evaluate the longitudinal effect of disease control on CHD risk factors
in acromegaly.
 in comparison with age- and gender-matched controls from the general
popullation
Patient and methods
Patients with acromegaly
 The acromegalic study population
 Recruited From the GPOS
 includes patients eligible for treatment with pegvisomant
 collects follow-up data during pegvisomant-induced disease
control.
 GPOS
 observational, multicenter, surveillance study to monitor safety
and efficacy of pegvisomant (=GH antagonist)
 comprises noninterventional data collection
 Data of the sixth interim analysis of GPOS (data close July
15, 2007) were evaluated for this study
Patient and methods
cross-sectional study and control population
 Cross-sectional study
 the criteria
 active acromegaly at baseline with elevated IGF-I levels
 complete risk factor assessment available at baseline
 no clinical evidence of ischemic heart disease (history,
symptoms, and resting EKG)
 age from 45–74 yr.
 A total of 133 acromegalic patients from GPOS fulfilling the
citeria
 Mean disease duration : 15.1±7.8 yr
 mean IGF-I levels at baseline were 1.74±0.72-fold ULN
 Control population
 were matched to 665 controls (ratio 1:5) from the HNR Study.
 HNR Study : to assess the prognostic value of modern risk
stratification methods, recruiting from general population
 for age and gender
Patient and methods
longitudinal study
 Longitudinal study
 Sixty-two of the 133 patients (31 men) with data available
from a 12 months follow up visit
 was treated with pegvisomant as monotherapy for acromegaly
 42 patients (62%) : Noramalized IGF-1 level
 controlled patients
 20 patients (38%) : reduced IGF-1 level
 partially controlled patients
Patient and methods
risk factor assessment
 GPOS
 Assessed by personal interview and lab measurements
 Cardiovascular medication :
 Lipid lowering medication
 Antihypertensive and antidiabetic medication (38%)
 BP : in supine position, manually according to the Riva-Rocci
method.
 DM : self reproted, taking an antidiabetic drug, PP2hr>200
 Hypercholesterolemia : total cholesterol levels that were 200
mg/dl or greater
 HNR study
 BP : in sitting position, automatic oscillometric BP device
 14% were on lipid-lowering medication,and 21% were on
antihypertensive medication
 Other : using the same criteria
Patient and methods
 Cardiac evaluation and determination of the FRS at 10 yr
 using the multivariate scoring system of the Framingham
Heart Study
 were stratified into low , intermediate , and high
midterm risk groups
 Statistical analysis
 Cross-sectional study : were compared by oneway ANOVA,
Mann-Whitney U test. or x2 test, as appropriate. given as odds
ratios with their95%confidence intervals
 longitudinal study : evaluated using Wilcoxon sign-rank test
and McNemar statistics as appropriate.
 Two sided P values 0.05 were considered significant.
results
Cardiac End Points
cross-sectional study
results
matched analysis
Results
..
Results
longitudinal analysis : HTN
Results
longitudinal analysis : FPG
Results
longitudinal analysis : FRS
 after 12 months of treatment with pegvisomant :
 controlled patients : 14.3 ± 7.2  10.8 ± 0.9% (P 0.19)
 partially controlled patients : 13.1 ± 8.3  12.6 ± 1.3% (P 0.62)
conclusion
 in a large cohort of patients with active acromegaly
compared with age- and gender-matched controls.
 hypertension and diabetes : increased prevalence
 HDL and LDL cholesterol levels : lower
 triglyceride levels were not different from the normal
population
 the FRS :increased risk of coronary artery disease only female
patients
 Control of acromegaly led to a significant improvement of
cardiovascular risk factors and to a reduction of the FRS in
both males and females