P13
Adherence with statins in a real-life setting is better when cardiovascular risk factors increase
T Couffinhal1, P Latry2, M Molimar3, B Begaud3, M Lafitte1, K Martin-Latry3
1
University Hospital of Bordeaux – Hospital Haut Leveque, Departement of Cardiology, Pessac, France, 2Direction Regionale du Service Medical de l'Assurance Maladie d'Aquitaine, CNAM-TS, Bordeaux, France, 3Inserm U 657, Universite Victor Segalen Bordeaux 2, Bordeaux, France
Topic: Pharmacoepidemiology
Background: Several studies have shown poor adherence to statin treatments and several associated factors have been highlighted: younger age, insufficient revenue, absence of cardiovascular morbidity, women, number of coprescribed drugs. While the factors for poor adherence have been highlighted, the impact of their combination on adherence is not clear. Purpose: To estimate adherence for statins and whether it differs according to the number of cardiovascular risk factors.
Methods: A cohort study was conducted using data from the French social security insurance database. Patients were included if they submitted a reimbursement form for a prescription for statins between September 1 and December 31, 2004, and did not receive any statin treatment for 6 months previous to this. Patients were followed up 15 months. Statin use was considered a proxy for hypercholesterolemia. the cohort was split into three groups according to their number of additional cardiovascular risk factors that included age and gender, diabetes mellitus and cardiovascular disease (using co-medications as a proxy). Adherence was assessed for each group by using four parameters: (i) proportion of days covered by statins, (ii) regularity of the treatment over time, (iii) persistence, and (iv) the patient s understanding of the treatment.
Results: 16,397 newly treated patients were identified. Of these statin users, 21.7 % did not have additional cardiovascular risk factors. thirty-one percent had two cardiovascular risk factor and 47% had at least three risk factors. All the parameters showed a sub-optimal adherence whatever the group: days covered ranged from 56 % to 72 %, regularity ranged from 23 % to 33 % and persistence ranged from 44 % to 59 %, but adherence was better for those with a higher number of cardiovascular risk factors.
Conclusions: the results confirm that long-term drug treatments are a difficult challenge, particularly in patients at lower risk.
P347
Atorvastatin worsens glucose metabolism and insulin sensitivity in hypercholester-olemic patients
K Koh1, Michae Quon2
1
Gachon University, Incheon, Republic of Korea 2NIH, Diabetes Unit, Bethesda, United States of America
Topic: Lipids and atherosclerosis
Background: We hypothesized atorvastatin, particularly at high dose, may increase insulin levels and worsen glucose metabolism with reducing plasma levels of adiponectin and insulin sensitivity in hypercholesterolemic patients.
Methods: this was a randomized, single-blind, placebo-controlled, parallel study. Age, sex, and body mass index were matched. Forty-four patients were given on placebo and 42, 44, 43, and 40 patients were given daily on atorvastatin 10, 20, 40, and 80 mg, respectively during a 2 month treatment period.
Results: Atorvastatin 10, 20, 40, and 80 mg significantly reduced LDL cholesterol (mean % changes; 39, 47, 52, and 56%) and apolipoprotein B levels (33, 37, 42, and 46%) after 2 months therapy when compared with baseline (all P<0.001 by paired t-test) or when compared with placebo (P<0.001 by ANOVA). Atorvastatin 10, 20, 40, and 80 mg significantly increased insulin (25, 42, 31, and 45%) and glycated hemoglobin levels (2, 5, 5, and 5%) from baseline (all P<0.05 by paired t-test) or when compared with placebo (P=0.009 for insulin and P=0.008 for glycated hemoglobin by ANOVA). Atorvastatin 10, 20, 40, and 80 mg decreased plasma adiponectin levels (4, 10, 3, and 9%) and decreased insulin sensitivity (1, 3, 3, and 4%) when compared with baseline (P=0.124, P=0.004, P=0.084, and P=0.040 for adiponectin; P=0.312, P=0.008, P<0.001, and P=0.008 for insulin sensitivity by paired t-test) or when compared with placebo (P=0.183 for adiponectin and P=0.033 for insulin sensitivity by ANOVA). However, the magnitude of these percent changes (glycated hemoglobin, insulin, adiponectin, and QUICKI) were not significantly different among the four different doses of atorvastatin despite dose-dependent changes in LDL cholesterol and apolipoprotein B reduction.
Conclusions: Atorvastatin significantly increased insulin and glycated hemoglobin levels and reduced insulin sensitivity in hypercholesterolemic patients independent of dosage and the extent of LDL cholesterol and apolipoprotein B reduction.
P348
Postprandial lipemia in familial combined hyperlipidemia, familial hypercholesterolemia and healthy subjects
A Pavlidis, G Kolovou, K Anagnostopoulou, P Petrou, K Sorodila, A Valaora, K Salpea, D Cokkinos
Onassis Cardiac Surgery Center, Athens, Greece
Topic: Lipids and atherosclerosis
Purpose: Familial combined hyperlipidemia (FCH) is the most common familial dyslipidemia among patients who suffer early myocardial infarction. Familial hypercholesterolemia (FH) is a monogenic disorder of lipid metabolism secondary to low density lipoprotein receptor mutations that has been strongly linked to premature coronary artery disease (CAD). Postprandial hypertriglyceridemia is also associated with CAD. the purpose of this study was to evaluate postprandial lipemia after an oral fat tolerance test (OFTT) in men with FCH and compare them to FH and healthy subjects.
Methods: the study population consisted of 83 subjects. OFTT was given to 34 men with FCH, 29 men with FH and 20 healthy men. the FCH and FH groups were further divided according to the lipid phenotype, on the basis of Fredrickson s classification, into five subgroups: FCH IIA (n=13), FCH IIB (n=10), FCH IV (n=11), FH IIA (n=21) and FH IIB (n=8). TG concentrations were measured before, 2, 4, 6 and 8 h after OFTT and the postprandial response was evaluated by the areas under the curve (AUC) for TG concentrations.
Results: the TG levels after OFTT were significantly higher in FCH compared to FH and healthy groups (AUC in mg/dl/h; 2678±1415 vs. 1503±1147 and 1011±652 respectively, p<0.001). the postprandial TG levels were significantly increased in FCH IV and FCH IIB groups compared to FCH IIA (AUC in mg/dl/h; 3220±824 vs. 3409±770 and 1863±577 respectively, p<0.001). FCH IIA group demonstrated higher TG levels at 2, 6 and 8h, compared to FH IIA group (p=0.05, p=0.017 and p=0.013 respectively). there were no significant differences between FH IIB and FCH IIB subgroups.
Conclusions: FCH and FH patients demonstrate an exaggerated postprandial response, that could partially contribute to the high cardiovascular risk. this abnormal response is even more pronounced in FCH subjects with a mixed lipid phenotype. these patients should be identified early and treated with the appropriate hypolipidemic regime.
(W) P349: Castelli risk index updated. Correlation between apolipoprotein B/apolipoprotein A1 and total cholesterol/HDL-cholesterol ratios in a healthy population
DA Siniawski, WM Masson, P Sorroche, W Scordo, L Casanas, J Krauss, AM Cagide
Italian Hospital of Buenos Aires, Buenos Aires, Argentina
Topic: Lipids and atherosclerosis
Background: Total cholesterol/HDL-cholesterol ratio (TC/HDLr) was proposed as a coronary risk marker approximately 25 years ago by Dr. W. Castelli and the goal suggested was <4.5. Recent studies demonstrated that apolipoprotein B/apolipoprotein A1 ratio (ApoB/ApoAr) is an independent coronary risk predictor. For various reasons, many patients can not access to apolipoprotein measurements. Objetives: Determine in a healthy population from Argentina TC/HDLr values corresponding to the decile 1 of the ApoB/ApoAr (0.43, odds ratio 1.00) in the INTERHEART study (IH). Suggest updated TC/HDLr goals to improvecoronary riskcateg-orization and targets in patients with high vascular risk.
Methods: Apolipoprotein levels were measured by kinetic nephelometry in samples obtained from blood givers. Correlations between ApoB/ApoAr and TC/HDLr were assessed. Two linear regression analyses models were performed for ApoB/ApoAr versus TC/HDLr: in the total population and in the very low risk subpopulation (sP) composed of non-smoking subjects with a body mass index <25. ROC analysis was done to assess the accuracy of the Castelli index to discriminate between subjets with ApoB/ApoAr > or =0.43. People with diabetes, hypertension, cardiovascular disease, or receiving lipid-lowering drugs were excluded.
Results: 283 subjets were included. Men: 64%, smokers: 31%, with ApoB/ApoAr >0.43: 82%. General characteristics (mean±SD): age: 42±14 years, BMI 26±4, TC 199±40 mg/dL, HDL-C: 49±13 mg/dL, TC/HDLr: 4.31±1.28, ApoB: 95.2±28 mg/dL, ApoA: 157.6±31 mg/dL, ApoB/ApoAr: 0.62±0.21. Correlations between ApoB/ApoAr and TC/HDLr in the total population and sP were: 0.90 and 0.91 respectively. In the lineal regression models ApoB/ApoAr value of 0.43 (decile 1 of IH) corresponded to a TC/HDLr of 3.22 and 3.17 in the total population and sP respectively. the AUC for the TC/HDLr for detecting an ApoB/ApoAr >0.43 was 0.936 (95% CI 0.897–0.975) and the optimal cut-off point 3.24 (sensitivity 91%, specificity 84%, positive predictive value 96%, negative predictive value 68%).
Conclusions: these results suggest that the Castelli index goal <4.5 should be revised and updated to <3.2. this target resembles the TC/HDLr observed in the decile 1 of the IH study.
P350
Lipid profile of Spanish patients with coronary heart disease treated with statins. Dyslipidemia International Study (DYSIS-SPAIN)
JR Gonzalez-Juanatey1, C Guijarro2, E Alegria3, JV Lozano4, B Gonzalez-Timon5, E Gomez-Salinas5, G Vitale5, J Millan6
1
University Clinical Hospital of Santiago de Compostela, Santiago de Compostela, Spain, 2Hospital Fundaciœn Alcorcœn, Madrid, Spain, 3University Clinic of Navarra, Pamplona, Spain, 4Health Centre Serreria 2, Valencia, Spain, 5Merck Sharp Dohme, Madrid, Spain 6University Hospital General Gregorio Maranon, Madrid, Spain
Topic: Lipids and atherosclerosis
Introduction: LDL-C is the therapeutic target for cardiovascular prevention and the NCEP ATP III guidelines recommend statins to reduce LDL-C levels. Patients with coronary heart disease (CHD) are considered as high cardiovascular risk; therefore they have a lower LDL-C target. Some studies have found that low HDL-C and high triglycerides (TGs) may have a role in coronary risk but statins have limited actionon them. the aim of this analysis was to describe the lipid profile of Spanish statin-treated patients with coronary heart disease (CHD).
Methods: Analysis of 3710 Spanish patients included in DYSIS, a cross-sectional study carried out with 22063 participants in Europe and Canada, on patients = 45 year-old treated with statins for at least 3 months. Data were recorded from patient's clinical charts. We used the ATP-III recommendations to classify patient's risk and define the LDL-C goal and normality or not of the HDL-C and triglycerides concentrations.
Results: In 3710 patients (median age 65.0 year-old, 47.3% women, 69.0% with hypertension, 39.0% with diabetes mellitus), 23.8% were diagnosed with CHD (68.0% men, 27.6% women, p<0,001); in this subpopulation 75.1% were hypertensive, 44.8% were diabetics, 16.8% were smokers and 25.6% had a family history of premature CHD. LDL-C was not at goal in 46.9% of patients with CHD vs. 51.4% of patients without CHD (p<0.05). the prevalence of low HDL-C (<40 mg/dl [men], <50 mg/dl [women]) was 34.9%, higher compared to patients without CHD (29.8%, p<0.001) and TGs were elevated in 35.1% comparing to 38.4% in patients without CHD. Lipid profiles were abnormal in 8.2% of CHD patients.
Conclusions: In this analysis of coronary heart disease patients, despite better control of LDL-C and TGs than the total Spanish population of the study, almost 50% of CHD patients do not reach LDL-C target; the prevalence of low HDL-C in these patients is significantly higher and one third show high TGs. A considerable number of CHD patients had an abnormal lipid profile; as a result it may be of interest to explore new therapies in order to reach LDL-C goal which may prevent cardiovascular disease with an integrated approach to other lipid risk factors as low HDL-C and high TGs.
P351
Prevalence of low HDL-C in statin treated patients with cardiovascular disease. the Dyslipidemia International Study (DYSIS-SPAIN)
E Alegria1, J Millan2, C Guijarro3, JV Lozano4, E Gomez-Salinas5, B Gonzalez-Timon5, G Vitale5, JR Gonzalez-Juanatey6
1
University Clinic of Navarra, Pamplona, Spain, 2University Hospital General Gregorio Maranon, Madrid, Spain, 3Hospital Fundaciœn Alcorcœn, Madrid, Spain, 4Health Centre Serreria 2, Valencia, Spain, 5Merk Sharp and Dohme, Madrid, Spain 6University Clinical Hospital of Santiago de Compostela, Santiago de Compostela, Spain
Topic: Lipids and atherosclerosis
Background and objective: Secondary prevention pretends to reduce cardiovascular (CV) events and to achieve it; multiple risk factors should be controlled as hypertension, obesity, diabetes or dyslipidemia. LDL-C is the usual target to treat dyslipidemia, but HDL-C has demonstrated to be a CV risk factor especially on coronary heart disease. the aim of this post-hoc analysis was to assess the prevalence of low HDL-C levels in statin treated patients with cardiovascular disease (CVD) included in DYSIS study.
Methods: Analysis of 3.710 Spanish patients included in DYSIS, a cross-sectional study carried out with 22.063 participants in Europe and Canada, on patient's = 45 year-old treated with statins for at least 3 months. Data were recorded from patient's clinical charts. We used the ATP-III recommendations to classify patient's risk and define the LDL-C goal and normality or not of the HDL-C and triglycerides concentrations.
Results: In 3710 Spanish patients (median age 65.0 year-old), 35.7% had established CVD (62.1% men and 34.0% women; p<0,001), of those 76.3% were hypertensive, 45.4% diabetics, 17.6% smokers and 24.6% had family history of premature coronary heart disease (CHD). LDL-C was not at goal in 51.1% of CVD patients vs 49.9% of non-CVD patients. the prevalence of low HDL-C (<40 mg/dl [men], <50 mg/dl [women]) was 35.7% and it was higher than in patients without CVD (26.4%, p<0.001) and 36.8% had elevated TG (=150 mg/dL) comparing to 38.2% in patients without CVD. the lipid profile was abnormal on 10.4% of CVD patients and it was significantly higher in women than men (14.3% vs 8.4%, p=0.01)
Conclusions: At this analysis, almost 50% of patients with CVD do not achieve LDL-C goal, despite statin treatment and a considerable amount show an abnormal lipid profile. Low HDL-C could be an important cardiovascular risk factor as the prevalence of HDL-C is higher on patients with cardiovascular disease. Treatment of low HDL-C added on statin therapy may help to prevent the development of cardiovascular events.
P352
Family history of premature myocardial infarction is associated with higher blood pressure in middle aged women
J Pitha1, M Lejskova2, P Stavek1, S Zecova3
1
Institute of Clinical and Experimental Medicine, Prague, Czech Republic, 2Institute for Postgraduate Medical Education, Prague, Czech Republic, 3Charles University Prague, 1st Faculty of Medicine, Prague, Czech Republic
Topic: Hypertension
Background: Many candidate genes for cardiovascular diseases are now intensively investigated. Nevertheless, family history is still one of the most important cardiovascular risk factors. We analyzed the impact of family history of premature myocardial infarction on cardiovascular risk factors in middle aged women.
Methods: Women aged 45–54 years representing 5% of population sample (n=883) underwent complete evaluation of cardiovascular risk factors. Positive family history was defined as a history of fatal/no fatal myocardial infarction in father before age of 60 and/or in mother before age of 65 years. Differences between these two groups were analyzed by unpaired t-test or by or ? 2 test (STATA).
Results: We found strong evidence, that women with positive family history (n=77) were more frequently treated for hypertension than women with negative family history (n=806) (40 vs. 27 %; p=0.018); had substantially higher systolic and diastolic blood pressure (123.5±18.0 vs. 118.5±18.0; p=0.009 and 82.1±10.0 vs. 78.5±10.0 mmHg; p=0.002); we also found weak evidence, that they had slightly higher plasma non-HDL cholesterol (4.1±1.1 vs. 3.9±0.9mmol/l; p=0.066) and apolipoprotein B (1.1±0.3 vs. 1.0±0.2 g/l; p=0.055). No other risk factors, including age, smoking behavior, history of diabetes, body mass index, waist circumference, glycaemia, C-reactive protein and other plasma lipids were associated with positive family history.
Conclusion: Family history of premature myocardial infarction was strongly associated with hypertension and blood pressure and weakly with non-HDL cholesterol and apolipoprotein B in middle aged women.
P353
Do particular types of left ventricular hypertrophy influence the duration and dispersion of QT interval in hypertensive patients?
J Kunisek1, L Zaputovic2, Z Cubranic2, L Kunisek2, V Persic1, A Ruzic1, M Zuvic Butorac3, S Vuckovic Rapaic1
1
thalassotherapia Opatija, Opatija, Croatia, 2Clinical Hospital Center Rijeka, Rijeka, Croatia, University of Rijeka, Technical Faculty, Rijeka, Croatia
Topic: Hypertension
Aim: the greater excitability of concentric and eccentric LVH types is a known fact. We sought to investigate the possible electrophysiological background (QT intervals and dispersion) of that phenomenon particulary in relation to the asymmetric type.
Methods: During the 5.5 years, 158 patients (70 men) with essential hypertension and without clinical evidence of ishaemic heart disease were included in the study according to prespecified criteria. All medication was discontinued 48 hours before exercise testing and Holter monitoring. Patients were divided into three groups with regard to LVH type: concentric (RWT>0.45 and IVS/LVPW=1.3), eccentric (LVISd>32 and RWT<0.45), asymmetric (IVS/LVPW>1.3), and three subgroups according to the degree of LVH: mild (IVS or LVPW 11–12 mm), moderate (IVS or LVPW 13–14mm) and severe (IVS or LVPW =15 mm). An upper normal limit for QTc interval was 420 ms for men and 430 ms for women; for QT dispersion it was 70 ms.
Results: the mean values of QT and QTc interval were borderline (380.6±47.3 ms and 425.0±34.4 ms, respectively), while the QT dispersion was normal (34.5±19.1 ms). the QTc interval and QT dispersion were increased in severe concentric and eccentric LVH (443 and 480 ms for QTc; 53 and 45 ms for QTd, respectively), but not significantly. QT dispersion in men with severe LVH was significantly enlarged (67.5 vs. 30 ms, p=0.047). the QT interval was significantly longer in patients with complex ventricular arrhythmias (p=0.037).
Conclusion: QTc interval and QT dispersion tend to increase proportionally to the left ventricular mass only in the concentric and eccentric type of LVH. this could explain the greater arrhytmogenicity of the concentric and eccentric in relation to the asymmetric LVH type.
P354
Acute and long-term effects of different intensity of exercise on blood pressure of hypertensive patients with chronic heart failure
G Caminiti, M Volterrani, A Cerrito, ME Lippi, B Sposato, A Franchini, A Arisi, G Rosano
IRCCS San Raffaele Pisana Hospital, Rome, Italy
Topic: Hypertension
Background: To evaluate if intervaal teraining (IT) is more effective than endurance training in improving exercise capacity blood pressure (BP) and heart rate of hypertensive subjects with chronic heart failure (CHF)
Methods: We enrolled 36 (M/F 22/14) CHF patients (NYHA class II) median age 62±7 ys. they were divided into 2 groups according to the exercise protocol. Group IT (20 patients): interval training (exercise between 50% and 80% of VO2 peak); group ET (16 patients) endurance training (exercise at 60% VO2 peak). the follow up period was 12 weeks. At baseline and 12 weeks patients underwent a cardiopulmonary test. A twenty-four hour ambulatory BPs was performed after the first and the last session of the exercise protocol.
Results: After the first exercise session there were not significant between groups differences on daytime and nighttime systolic BP and diastolic BP. After 12 weeks of training VO2 peak increased in both groups in a similar manner (IT+13; ET+11%; p0.18). ET group had a greater increase of time of exercise (+173 sec vs +112 sec; p 0.03) than ET group. ET had a lower reduction of rest heart rate (–4 bpm vs 9 bpm) and a lower improvement of heart rate recovery al I minute (–6.2 bpm vs –11.3 bpm; p0.01) After the last session IT group had a greater reduction of daytime (–16% vs 7; p 0.02) and nighttime (–19% vs 8; p 0.006) diastolic blood pressure, and lower daytime (–12% vs 9; p 0.07) and nighttime (–13% vs 6; p 0.002) heart rate than ET group.
Conclusions: IT seems to determine greater effects on exercise capacity and blood pressure control in hypertensive patients with CHF.
P355
Metabolic disorders in patients with arterial hypertension (AH) and metabolic syndrome (MS) depending on blood pressure (BP) and intima-media thickness
O Rekovets, YM Sirenko, SY Savitskiy, EA Pavluyk, AS Vaschylko, GF Primak
National Scientific Center “M.D. Strazhesko Institute of Cardiology, MAS of Ukraine”, Kiev, Ukraine
Topic: Hypertension
Background: It is not clear relation ship between degrees of manifestation insulin resistance and increased blood pressure and atherosclerosis in patients with arterial hypertension (AH) and metabolic syndrome (MS).
Objection: to evaluate the changers of some characteristics of insulin sensitivity in patients with AH and MS and intima-media thickness and increased blood pressure.
Methods: We studied on 124 patients (52 men and 72 women) with average age 50.3±1.0 years old with mild to moderate AH and clinical signs of MS (according to ATP III), patients with diabetes mellitus were excluded from the study. All patients were performed oral glucose tolerance test (OGTT) with estimation of serum glucose and insulin level and calculation of HOMA index, the total cholesterol, triglycerides (TG), HDL cholesterol determination, calculated body mass (BMI index), measured office BP, and ABMP (Ambulatory Blood Pressure Monitoring) estimated intima-media thickness (IMT).
Results: 36 patients (29%) had insulin resistance (IR) with HOMA >3. 88 patients (71%) had not insulin resistance (HOMA <3). Patients with HOMA >3 had higher BMI 34,60 ± 0,82 kg/m2 than patients without IR 32,21 ± 0,40kg/m2 (p<0,001). Patients who had insulin resistance had higher BP than who did not have insulin resistance: office SBP 157,72 ± 1,56 vs 156,16 ± 0,91 mmHg, p<0,001, office DBP 92,06 ± 0,60 vs 91,22 ±0,38 mmHg, p < 0,01. ABMP SBP 135,79 ± 2,12 vs 133,94 ± 1,33 mmHg, p<0,001, DBP 81,22 ± 1,45 vs 80,45 ± 0,98 mmHg. Patients with IR had higher cholesterol and TG and HDL less than patients without IR: cholesterol 6,79 ± 0,15 vs 6,23 ± 0,12 mmol/l, p<0,01, TG 2,12 ± 0,20 vs 1,71 ± 0,60 mmol/l, p<0,01, HDL level 1,13 ± 0,03 vs 1,19 ± 0,02 mmol/l, p<0,01. Patients with IR hah more aggressive atherosclerosis compared without IR patients. Patients with HOMA > 3 had IMT 1,52 ± 0,01 vs 1,27 mm, p<0,01, who had HOMA < 3.
Conclusions: Patients with AH and insulin resistance had higher body mass index, office blood pressure and BP during ABMP, level of cholesterol, triglycerides, intima-media thickness (IMT) and less HDL cholesterol compared patients without insulin resistance.
P356
Plasma brain natriuretic peptide: a biochemical marker of effective blood pressure management in pregnancy
A Ascione1, F Stoppoloni1, G Vernetti1, A Sciarappa1, M Borgia1
1
Buon Consiglio Fatebenefratelli Hospital, Naples, Italy, 2Vincenzo Monaldi Hospital, Naples, Italy
Topic: Hypertension
Objective: To investigate plasma brain natriuretic peptide (BNP) concentrations in association with blood pressure (BP) in pregnant women at baseline and after antihypertensive drug treatment.
Patients and methods: We prospectively examined 86 women with newly diagnosed essential hypertension without target organ damage by blood pressure holter monitoring, whose mean age was 27.7 +/– 10.9 years. they were before three months gone with child. Mean blood systolic/diastolic pressure in 24 hours was 146,5/98,8 mmhg. Treatment initiation began with metildopa 250 mg/bis in day and was doubled at 4 weeks in cases of inadequate BP control. If indicated, at 8-week-follow-up metildopa 500 mg/bis in die alone or with nyphedipine 30 mg was added. BNP levels were measured at baseline and after 2 months of antihypertensive treatment.
Results: At baseline plasma BNP levels were found to be related to systolic BP (r = 0.27, P<0.001), independent of age, weight, smoking status, and left ventricular mass index estimated by echocardiography (P = 0.002). Additionally, higher BNP concentrations were observed in patients with stage 2 hypertension compared with those with stage 1 (median 34.9 vs. 25.9 pg/ml, P = 0.022). Multivariate analysis showed a positive association between BNP and systolic BP variability (P = 0.034). At follow-up, 60.1% of the participants who had achieved BP control showed decreased BNP levels in contrast to those with poor BP control (median change –14.5 vs. –1.3 and median range from –34.4 to –4.4 vs. –9.6 to 10.9, respectively, P<0.001).
Conclusion: In this hypertensive population of pregnant, increased BNP concentrations are associated with higher BP levels and systolic BP variability. the fall of BNP observed in those who achieved BP control indicates that BNP could be used as a biochemical marker of effective BP control and target organ protection
P357
Correlations between the metabolic syndrome and other cardiovascular risk factors on the outcome of hypertensive patients
E Belu1, R Musetescu1, A E Musetescu2, V Belu3, D -D Ionescu1, V Mechirova4
1
Cardiology Center, Craiova, Romania, 2University of Medicine and Pharmacy of Craiova, Craiova, Romania, 3Cardiology Depart., Campulung, Romania, 4University of Medicine, Kosice, Slovak Republic
Topic: Hypertension
Purpose: the metabolic syndrome (MS) includes several interrelated cardiovascular risk factors that have been shown to increase the risk of heart disease. Taking into account the numerous cases of patients suffering from hypertension and metabolic syndrome (MS) in this area and the short data regarding the profile of the romanian hypertensive patient, we have propounded to assess the risk profile for these patients.
Method: We have included in the study group patients admitted in Craiova Cardiology Center in 2007 from the County registry of hypertension and we have divided them in 2 subgroups: individuals with hypertension and metabolic syndrome according to NCEP criteria and the second subgroup of hypertensives without metabolic syndrome. the follow-up period lasted for two years. We performed multivariate logistic regression analyses in order to assess the relationships between hypertension, metabolic syndrome, target organ disease, dyslipidemia, visceral obesity and diabetes mellitus.
Results: We have evaluated 542 patients with metabolic syndrome and hypertension mean age of 55,12 years. there were 48,72% men and 51,28 % women. the risk of end stage renal disease was estimated at 2,56%. the profile of our MS patients was depicted by older age, higher systolic pressure, higher body mass indexes the procent of patients with diabetes mellitus was 34,19%, but 27,35% from them had impaired fasting glucose. this population had more left ventricular hypertrophy, renal and cardiac diseases were more prevalent (p<0.01), and they received more antihypertensive drugs (p<0.05). there were only 17,09% from our patients who achieved the target values of blood pressure.
Conclusions: the study shows the poor adherence to treatment of hypertensive patients with metabolic syndrome. these patients are achieving the target values for blood pressure in a very small percent. the number of important cardiovascular events is increased in the case of these young patients with a very high risk profile.
P358
Trends in threshold SBP and its impact on mortality in the hypertensive patients in 25 years of follow-up
UO Andersen, GB Jensen
Copenhagen City Heart Study, Copenhagen, Denmark
Topic: Hypertension
Aims: To evaluate trends in threshold SBP (the SBP-value before start of antihypertensive therapy) and to evaluate the impact of threshold SBP on mortality.
Design and methods: Copenhagen City Heart Study is a prospective longitudinal epidemiological study. the study population consists of subjects that in the next survey start antihypertensive therapy. the subjects were followed over 25 years with 1 to 4 measurements on each subject. the BP measurement was fully standardised and measurement method was unchanged throughout the observation period. A questionnaire concerning risk factors and medical therapy exercise was completed by the participants and double-checked by the technicians. Data were analysed by random effect model for trends and by Cox analysis.
Results: threshold SBP did not change during 25 years of follow-up. Men, obese and elderly started antihypertensive therapy at a higher threshold value than their counterparts. Mortality increased by increasing threshold value.
Conclusion: Hypertensive patients that start treatment on low SBP-values survive better that the patients that start antihypertensive treatment on high SBP values. In the past 25 years threshold SBP has not decreased. It is essential to start antihypertensive therapy earlier if we want to improve life expectancy in the hypertensive population.
P359
the relationship between the sleep quality and blood pressure values before and after therapy with rilmenidine
S Farsky, R Sidlo
Slovak League against Hypertension, Martin, Slovak Republic
Topic: Hypertension
the study was aimed at determining a potential correlation between the morning values of blood pressure and the sleep quality during the previous night in patients with fixed hypertension treated with medicaments, and at finding whether a therapy with rilmenidine has positive effects not only on the value of blood pressure, but also improves the sleep quality through decrease in the sympathicus activity.
We have examined 993 patients with essential hypertension, that have not reached the target values of blood pressure in spite of a therapy with medicaments, and the abdominal obesity was found in 79% of the patients. the therapy with rilmenidine was added to their previous treatment, and the study duration was 3 months. At the beginning and at the end of the study, there were performed anthropometric and basic biochemistry examinations, a repeated measurement of the blood pressure and heart rate in 10 min intervals in outpatient departments of general practitioners, as well as an evaluation of the sleep quality according to the Athens Insomnia Scale questionnaire.
After adding rilmenidine to their hypertension therapy, there was found a decrease in systolic pressure, diastolic pressure, heart rate and sleep quality. the decrease was highly significant (p<0.0001). the coefficients of correlation between the systolic blood pressure values and the sleep quality were 0.08 (p<0.0226) at the beginning of the study and 0.14 (p < 0.0001) at the end of the study, and were 0.08 (p<0.015) between the diastolic blood pressure values and the sleep quality at the end of the study. the coefficients of correlation between a difference of the systolic blood pressure values and a difference between results of the questionnaire at the beginning and the end of the study were –0.09 (p< 0.0064).
Results of our study acknowledged a positive effect of rilmenidine in hypertension therapy due to a significant decrease of the blood pressure, slowing the heart rate and improvement of the sleep quality evaluated by the standardized questionnaire. In addition, interesting associations were found between the sleep quality and values of the systolic blood pressure, and partly also diastolic blood pressure before the start of therapy with rilmenidine and during the therapy. these results are in concordance with the actual literature data that demonstrated that a decreased length and an impaired quality of sleep have a negative effect on blood pressure values and occurrence of hypertension as well as the overall cardiovascular risk in adolescent and adults persons.
P360
High prevalence of prehypertension and hypertension among young and middle-aged bank employees in Hungary
S Steiner1, E Helis1, JG Fodor1, P Turton1, S Sonkodi2, B Sonkodi2
1
University of Ottawa Heart Institute, Ottawa, Canada, 2SZTE, AOK, I. Belgyógyászati Klinika, Szeged, Hungary
Topic: Hypertension
Purpose: Hungary has one of the highest mortality rates due to strokes among the European Union countries. As elevated blood pressure (BP) is the principal risk factor for strokes, we assessed BP levels in a sample of working population in Budapest, Hungary.
Methods: 1000 bank employees (mean age±SD =32.5±8.1) were screened for their BP and other CV risk factors at their worksite. the respondents included 304 males (mean age±SD =30.9±6.4) and 696 females (mean age±SD =33.2±8.9). Respondents were classified as normotensives, prehypertensives (PHTN) and hypertensives (HTN) according to their BP levels. the BP and heart rate (HR) were measured using an automated instrument. Body height, body weight and waist circumference (WC) were measured and BMI was calculated. Self-reported information regarding smoking was recorded. Group comparisons were made by ANOVA followed by Tukey s post hoc test.
Results: 46% of respondents were identified as PHTN (systolic blood pressure (SBP) between 120–139 mmHg or diastolic blood pressure (DBP) between 80–89 mmHg) and 17.3% as HTN (SBP = 140 mmHg and/or DBP = 90 mmHg and/or on hypertensive medications). A progressive and significant increase in HR, WC and BMI was ascertained as BP levels increased (see Table). Interestingly, no age difference was found between normotensives and PHTN, while HTN individuals were significantly older. Almost a third (29%) of all respondents were smokers. Conclusions: the high prevalence of elevated BP and smoking might provide a partial explanation for the excessive stroke mortality and unfavourable cardiovascular profile of Hungary as compared with other European countries.
All data are shown as mean± SD.∗P < 0.0001 for comparison against normotensives.# P < 0.0001 for comparison of PHTN vs. HTN.
P361
the influence of depression disorders on the blood pressure in adolescents
V Romero, J Villasmil, E Silva, G Bermudez
Instituto de Enfermedades Cardiovasculares, Maracaibo, Venezuela
Topic: Psychosocial factors and stress
Objective: To determine the effects of depression on the blood pressure (BP) in adolescents.
Methods: this study was carried out in a random sample of schools from Maracaibo, Venezuela. the participants were 560 adolescents, males (n= 310) and females (n= 250), age-mean = 14.19 years (SD=1.52), who were systolic and diastolic BP recorded in two schools day, in sitting position and using oscillometric method (Dinamap). the adolescents completed the Zung self-rating depression scale to assess depression symptoms, and they were classified according the result of this scale in 3 categories: Normal (N), Minimum Depression (MiD) and Moderate Depression (MoD). Statistics Methods: the data are presented as mean ± standard deviation. the One-way ANOVA was used to study the effects of the different depression categories on the BP levels, and the Tukey test was applied for the mean comparisons.
Results: the prevalence of MoD was 8.2% (n=46) and it was 28.2% (n=158) for MiD in all subjects. the systolic/diastolic BP values were: 103.1± 10.3/57.6±5.6 mmHg in adolescents with MoD, 106.8±12.2/60.7±6.9 mmHg in subjects with MiD and 108.6±12.2/60.5±6.7 mmHg in N adolescents. the ANOVA showed statistically significant effects of the depression disorders on both systolic BP (F = 4.816) and diastolic BP (F = 4.384). the analysis post hoc evidenced systolic and diastolic BP values statistically lower in adolescents with MoD than those with MiD (p<0.01) or N (p<0.01).
Conclusions: the present results provide evidence for an association between depression disorders and low BP in the adolescent population. this study do not evaluated the mechanism behind the findings; however, it is possible that there is a relationship between symptoms of depression and some indications of abnormal autonomic nervous function; this abnormality would explain the low BP. More investigations are needed to explore these associations in adolescents.
P362
Correlates of nondipping blood pressure pattern among middle-aged men and women
E Clays1, D De Bacquer1, K Van Herck1, M De Buyzere2, M Kornitzer3, F Kittel3, G De Backer1
1
Ghent University, Ghent, Belgium, 2Ghent University Hospital, Ghent, Belgium, 3Free University of Brussels (ULB), Brussels, Belgium
Topic: Cardiovascular epidemiology
Purpose: there is a growing body of evidence suggesting that nondipping (i.e. a lack of nocturnal blood pressure (BP) fall) has prognostic value for cardiovascular disease (CVD). Knowledge of the underlying mechanisms and associative factors is still incomplete. Some sociodemographic and behavioral factors have been shown to correlate with nondipping, while very little is known about psychosocial correlates. the aim of this study was to examine correlates of nondipping in a sample of healthy middle-aged workers.
Methods: Results are based on observations in 170 day-time workers (60% male, mean age 51 years) from the Belstress II study with no history of CVD. Socio-demographic (gender, age, educational level), behavioral (smoking status, alcohol consumption, physical activity, sleep pattern) and psychosocial factors (job stress according to the Demand-Control model, and symptoms of depression, anxiety and vital exhaustion based on the CES-D scale) were assessed by means of questionnaires. Height and body weight were measured during standardized bio-clinical examinations. On a regular working day, participants wore an ambulatory BP monitor (Spacelabs Medical) during 24 hours. Nondipping was defined as a decline from wake to sleep BP of less than 10%. Associations were studied bymultiple logistic regression analysis. Results: Nondipping in systolic blood pressure (SBP) was present in 22% and nondipping in diastolic blood pressure (DBP) in 9% of the study sample. the prevalence of nondipping was higher in females, lower educated and obese persons. After adjusting for gender, educational level and body mass index, the risk for nondipping in SBP was (borderline) significantly increased by high symptoms of depression (OR = 2.25; 95% CI = 0.97–5.23), anxiety (OR = 3.32; 95% CI = 1.43–7.72) and vital exhaustion (OR = 2.24; 95% CI = 0.89–5.60), while nondipping in DBP was (borderline) significantly related to sleep problems (OR = 2.68; 95% CI = 0.85–8.40), job strain (defined as the ratio of demands over control) (OR per 1 SD in job strain = 1.74; 95% CI = 1.10–2.77), high symptoms of depression (OR = 2.83; 95% CI = 0.90–8.94) and vital exhaustion (OR = 2.99; 95% CI = 0.90–9.96). No associations were found with age, smoking, alcohol consumption and physical activity.
Conclusions: this study found that nondipping was associated with female gender, lower educational level, obesity, sleep problems, job strain, and symptoms of depression, anxiety and vital exhaustion in a sample of middle-aged workers. the role of psychosocial factors should be considered when examining nondipping.
P364
Factors associated with prediabetes in adult children of patients with premature coronary heart disease; the study of families of patients with premature coronary heart disease
MV Konnov, LM Dobordzhginidze, AD Deev, NA Gratsiansky
Institute of Physico-Chemical Medicine, Moscow, Russian Federation
Topic: Diabetes
Objective: To elucidate associations of impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) in adult children of patients with premature coronary heart disease (CHD) and/or elevated low density lipoprotein cholesterol (LDL-C) with some their own characteristics and those of their parents.
Methods: We examined members of 210 families of patients with premature CHD (91.4%) and/or with LDL-C =3.36 mmol/l including 136 consorts of patients-probands, and 251 children aged 16–37 years. Children had neitherovert vascular disease nor diabetes mellitus (DM). Characteristics analyzed included tobacco smoking, alcohol consumption, oral contraceptives use, height, body mass index, waist circumference, heart rate (HR), systolic/diastolic BP, total and high density lipoprotein cholesterol, LDL-C, triglycerides, serum basal glucose, IFG, IGT, DM (ADA criteria) and (in parents) education level and menses. High BP was defined as pre-hypertension or hypertension (NHBPEP-4 or JNC-7 depending on age). IFG and IGT of children were combined and designated prediabetes (preDM). Associations were assessed by logistical regression analysis with age, sex adjustment.
Results: PreDM was found in 35 of 251 children (13.9%). DM of neither parent-proband nor of any parent was related to preDM in children. Factors related to the presence of preDM with p<0.1 in univariate analysis (children s high BP, HR, triglycerides, waist circumference, alcohol consumption of proband, and basal glucose, diastolic BP, metabolic syndrome, height and waist circumference of non-proband) were included into stepwise regression procedure. Characteristics independently linked with preDM turned out to be own high BP; basal glucose of non-proband; and own HR (table).
Conclusion: In this group of grown-up children of patients with premature CHD: 1) preDM was not related to DM of their parents; 2) preDM was not related to any studied characteristic of parent with premature CHD; 2) basal glucose of parent – nonproband, and own high BP and HR were independently associated with preDM.
P365
Risk factors for cardiac autonomic neuropathy in diabetes and the significance of a multifactorial intervention for its prevention
C Voulgari1, M Psallas1, A Kokkinos1, V Argiana1, I Moyssakis2, D Perrea3, N Katsilambros1, N Tentolouris1
1
First Department of Propaedeutic Medicine, Athens University Medical School, Laiko General Hospital, Athens, Greece, 2Laiko General Hospital, Department of Cardiology, Athens, Greece, 3Laboratory for Experimental Surgery and Surgical Research, Athens University Medical School, Athens, Greece
Topic: Diabetes
Purpose: Cardiac autonomic neuropathy (CAN) is a common diabetes complication and confers an increased cardiovascular risk Literature data on the association between CAN with clinical and metabolic correlates in diabetic subjects are limited, especially in type 2 diabetes. We aimed to examine the relationship between CAN with clinical and metabolic parameters, and other diabetes complications.
Methods: We consecutively recruited 1000 diabetic subjects (type 1 diabetes=400; type 2 diabetes=600). Participants with overt nephropathy, and macrovascular complications were excluded. CAN was diagnosed when two out of the four classical autonomic function tests were abnormal.
Results: In type 1 diabetes, multivariate logistic regression analysis, after adjustment for gender, age, central fat distribution, diabetes duration and lipids demonstrated that the odds (OR, 95% confidence intervals) of CAN increased with factors such as pubertal diabetes onset [1.08 (1.03–1.24), P<0.001], higher central fat distribution [1.36 (1.01–2.02, P=0.03], higher blood pressure [1.16 (1.03–1.05), P=0.01], HbA1c [1.69 (1.07–2.76), P=0.02] and fasting glucose levels [1.01 (1.00–1.01), P<0.001], higher LDL-cholesterol [1.01 (1.00–1.02), P=0.03] and triglycerides levels [1.58 (1.24–1.48), P=0.03], microalbuminuria [1.24 (1.12–1.36), P=0.02], retinopathy [1.13 (1.04–1.41), P=0.01] and smoking [1.10 (1.02–1.40), P=0.02]. the same analysis in patients with type 2 diabetes, after adjustment for gender, age, blood pressure, lipids, and antidiabetic treatment demonstrated that central fat distribution [1.08 (1.00–1.39), P=0.02], longer diabetes duration [1.20 (1.09–1.34), P=0.006], higher HbA1c [1.19 (1.02–1.38), P=0.02], fasting glucose [1.21 (1.12–1.31, P=0.002)], LDL-cholesterol [1.35 (1.04–1.75), P=0.02], triglycerides levels [1.30 (1.00–1.68), P=0.03], microalbuminuria [1.20 (1.14–1.36), P<0.001], retinopathy [1.24 (1.16–1.35), P=0.008], smoking [1.22 (1.14–1.49), P<0.001] and smoking severity (>20 cigarettes/day) [1.32 (1.26–1.64), P<0.001] were independently associated with higher odds of CAN.
Conclusions: In type 1 diabetes, the risk of CAN is associated with pubertal diabetes onset, worse glycaemic control, higher blood pressure levels, and dyslipidaemia, presence of microvascular complications and smoking. In patients with type 2 diabetes the risk of CAN increased with central fat distribution, longer diabetes duration, worse glycaemic control, dyslipidaemia, retinopathy and/or microalbuminuria, smoking and smoking severity. Our findings emphasize the need for a multifactorial intervention for the prevention of CAN in diabetes.
P366
Absence of gender influence on the prognosis of diabetic patients in an outpatient setting, the Barbanza Diabetes Study
R C Rafael CarlosVidal Perez, F Otero-Ravina, E Rodriguez Moldes, C De Frutos, L Vaamonde, L Grigorian Shamagian, P Mazon Ramos, JR Gonzalez-Juanatey
University Clinical Hospital of Santiago de Compostela, Santiago de Compostela, Spain
Topic: Diabetes
the Barbanza Diabetes Study group
Purpose: Previous data have shown that in the patients of male sex, the diabetes mellitus has a lesser impact over the cardiovascular prognosis. the aim of our study was to assess the influence of the gender and prior cardiovascular disease on the prognosis of diabetic patients in an outpatient setting.
Methods: Multicenter prospective cohort study involved 1423 consecutive patients with diabetes mellitus who were recruited by 31 primary care physicians. the patients characteristics were recorded and they were followed up for 45±10 months.
Results: We studied patients (50% male) with mean age 66 years old. Women were significantly older (67 vs. 64 years, p<0.001) and with more risk factors (64 vs. 53% with more than one, p<0.01) compared with men. Women had less prior cardiovascular disease (24 vs. 29%, p<0.05) or microalbuminuria (32 vs 44%, p<0.001) in this cohort. there were also differences in treatment, women had more renin-angiotensin blockade drugs (60% vs. 50%, p<0.01) and insulin prescribed (20 vs. 11%, p<0.001). At the end of follow up there were no significant differences on cardiovascular mortality (women 2.4% and men 3.7%, p=0.354) or cardiovascular hospital admissions (12.5% vs. 14.8%, p=0.351). On the other hand a greater cardiovascular mortality in patients with prior cardiovascular disease was found (6.1 vs 2.1%, p<0.05), but in this group there were not gender related differences. We adjusted by age, risk factors and treatment this last finding and we didn't find differences between both sexes in the cardiovascular event rate (death, admissions) with a hazard ratio 0.64 (95% confidence interval 0.38–1.08), and neither differences in patients without prior cardiovascular disease were found. the age and microalbuminuria were, in both sexes, the only significant prognosis factors for outcome.
Conclusion: the cardiovascular impact of diabetes is the same in men and women in our outpatient setting; this finding could justify the absence of gender differences in the strategies of cardiovascular prevention in diabetic patients.
P367
Increased ventricular arrhythmogeneity in subjects with type 2 diabetes and cardiac autonomic neuropathy: assessment of the ventricular gradient
C Voulgari1, I Moyssakis2, P Dilaveris3, D Perrea4, D Papadogiannis1, C Stefanadis1, N Tentolouris1
1
First Department of Propaedeutic Medicine, Athens University Medical School, Laiko General Hospital, Athens, Greece, 2Laiko General Hospital, Department of Cardiology, Athens, Greece, 3Department of Cardiology, Hippokration General Hospital, Athens University Medical School, Athens, Greece, 4Laboratory for Experimental Surgery and Surgical Research, Athens University Medical School, Athens, Greece
Topic: Diabetes
Purpose: Cardiac autonomic neuropathy (CAN) is a common diabetes complication associated with dispersion of ventricular repolarization and arrhythmia provocation. QT-prolongation has often been criticized as a poor indicator of ventricular arrhythmogeneity. the spatial QRS-T angle (spQRS-Ta) is a novel vectorcardiographic marker, akin to the concept of the ventricular gradient, a robust index of ventricular electrophysiological heterogeneity and a dominant predictor of cardiovascular morbidity and mortality. We examined differences in the spQRS-Ta in subjects with type 2 diabetes (T2DM) with and without CAN.
Methods: A total of 232 subjects with T2DM (105 with CAN and 127 without CAN) (age 58.4±9.1 years) and 232 matched (by age and sex) controls were studied. Diagnosis of CAN was based on the classical autonomic function tests. All subjects underwent a digital 15-min ECG and 30-min heart rate recordings. ECG parameters were measured using the MEANS program. Indices of the heart rate variability (HRV) were obtained using the VariaCardio system. Ankle-brachial-pressure index (ABI), LV mass index (LVMi) and myocardial performance index (Tei-index) were assessed by ultrasonography.
Results: the spQRS-Ta was higher in the subjects with T2DM in comparison with the controls (24.5±10.7 vs. 9.7±4.5, P<0.001) and in the subjects with CAN than in those without CAN (30.1±11.3 vs. 19.5±7.1, P<0.001). No differences were found in the QT-interval between the studied groups. Multivariate linear regression analysis in the subjects with T2DM demonstrated independent associations between the spQRS-Ta, the presence and the severity of CAN (P<0.001), HbA1c (P<0.001), duration of diabetes (P=0.004), HOMA-IR (P<0.001), diabetic cardiomyopathy (P=0.02) and sympatho-vagal imbalance (P<0.001).
Conclusions: the spQRS-Ta is increased in patients with T2DM and CAN, suggesting ventricular repolarization heterogeneity. the metabolic and cardiovascular factors associated with the presence of CAN in diabetes (duration and degree of hyperglycaemia, diabetic treatment) were also independently associated with ventricular arrhythmogeneity, assessed by spQRS-Ta. SpQRS-Ta was also independently associated with the structural and functional substrate involved in diabetic cardiomyopathy. QT and its parameters were found to be impaired by CAN. SpQRS-Ta is an effective, noninvasive, low-cost test for the early detection of CAN and prospective studies will further show if its determination can help clinicians better stratify diabetic individuals and prevent CAN s clinical manifestations and symptoms that may cause lethal outcomes.
P368
Atorvastatin worsens glucose metabolism and insulin sensitivity in patients with metabolic syndrome/type 2 diabetes
K Koh1, M Quon2
1
Gachon University, Incheon, Republic of Korea, 2NIH, Diabetes Unit, Bethesda, United States of America
Topic: Diabetes
Background: We compared the effects of atorvastatin on glucose metabolism and insulin sensitivity in hypercholesterolemic patients with and without metabolic syndrome/diabetes.
Methods: Randomized, single-blind, placebo-controlled, parallel study. Age, sex, and body mass index were matched. Forty-four patients were given on placebo and 42, 44, 43, and 40 patients were given daily on atorvastatin 10, 20, 40, and 80 mg, respectively during a 2 month treatment period. Nineteen patients on placebo and 18, 18, 20, and 18 patients on atorvastatin 10, 20, 40, and 80 mg were metabolic syndrome/diabetes.
Results: Atorvastatin 10, 20, 40, and 80 mg significantly reduced LDL cholesterol (median % changes; 39, 47, 52, and 54%) and apolipoprotein B levels (31, 37, 44, and 48%) after 2 months therapy when compared with baseline (all P<0.001 by paired t-test) or when compared with placebo (P<0.001 by ANOVA). Atorvastatin 10, 20, 40, and 80 mg significantly increased insulin (27, 63, 36, and 58%) and glycated hemoglobin levels (4, 7, 7, and 8%) from baseline (all P<0.05 by paired t-test) or when compared with placebo (P=0.011 for insulin and P=0.004 for glycated hemoglobin by ANOVA). Atorvastatin 10,20,40, and 80 mg decreased plasma adiponectin levels (0, 18, 2, and 11%) and decreased insulin sensitivity (2, 6, 4, and 6%) when compared with baseline (P=0.732, P=0.024, P=0.508, and P=0.128 for adiponectin; P=0.233, P=0.012, P=0.008, and P=0.003 for insulin sensitivity by paired t-test) or when compared with placebo (P=0.147 for adiponectin and P=0.006 for insulin sensitivity by ANOVA). However, the magnitude of these percent changes (glycated hemoglobin, insulin, adiponectin, and QUICKI) were not significantly different among the four different doses of atorvastatin despite dose-dependent changes in apolipoprotein B reduction. these effects were not significantly different between patients with and without metabolic syndrome/diabetes.
Conclusions: Atorvastatin significantly increased insulin and glycated hemoglobin levels and reduced insulin sensitivity in hypercholesterolemic patients with metabolic syndrome/diabetes independent of dosage and the extent of apolipoprotein B reduction.
P369
Type 2 Diabetes Mellitus: a true coronary artery disease risk equivalent?
SNC Barra, J Silva, P Gomes, R Providencia, L Seca, A L Marques
Hospital Center of Coimbra, Coimbra, Portugal
Topic: Diabetes
Purpose: Several studies have suggested the risk of mortality is equivalent for non-diabetic patients with known coronary artery disease (CAD) or previous myocardial infarction (MI) and for diabetic patients without previous known CAD or MI. this study aims to investigate the prognostic power of diabetes mellitus (DM) and CAD in predicting cardiovascular (CV) risk following a MI.
Methods: 178 consecutive patients (70.5±11.7 years old, 64% males) with DM or known CAD admitted with a MI. Data collected: admission glycemia, creatinine, haemoglobin [Hb] and C Reactive Protein (PCR); maximum troponin levels (MaxTrop); glomerular filtration rate (GFR) by MDRD formula; maximum Killip Class (mKC); CAD extension; GRACE risk score (GS). Patients were followed for 24 months. Patients were divided in 2 groups (Group A diabetics without known CAD; Group B: non-diabetics with previous known CAD).
Results: Patients of Group A had significantly higher: intra-hospital mortality (17.7% vs 6.2%, p=0.03, OR 3.33), GS (173.9 vs 157.2, p=0.027), risk for acute heart failure (50.4% vs 33.9%, p=0.032, OR 1.99); average mKC (1.92 vs 1.60, p<0.001), PCR (4.52 vs 1.37, p=0.004) and, as expected, admission glycaemia (12.62 vs 7.21). Patients in both groups did not differ in admission Hb, MaxTrop (despite a trend for higher MaxTrop in group A; 52.3 vs 40.9, p=0.2), creatinine, GFR and, surprisingly, CAD extension (the number of arteries and segments with significant stenotic lesions was not significantly different in both groups). Cardiovascular risk during follow-up was similar in patients from both groups, as evidenced by a similar mortality rate, risk for recurrent angina, reinfarction, stroke and decompensated heart failure.
Conclusions: Diabetic patients without previous known CAD had a higher mortality rate and a higher risk for acute heart failure. However, DM was truly a CAD risk equivalent in what concerns myocardial necrosis extension and CAD severity as analyzed by coronariography. Also, CV risk during a 2 year follow-up was not significantly different in both groups, attesting the equivalence between DM and known CAD. this highlights the importance of aggressive therapeutic approach for all diabetic patients with a MI.
P370
Difference of positive remodeling area between DM and non-DM heart disease subjects
Y Miyaishi, H Adachi, J Murakami, H Hoshizaki, S Oshima
Gunma Prefectural Cardiovascular Center, Maebashi, Japan
Topic: Diabetes
Background and Purpose: Compensatory enlargement of coronary artery is frequently investigated in patients with angiographically normal coronary arteries by intracoronary ultrasound examinations (IVUS). Although diabetes mellitus (DM) is well known to be one of the coronary risk factors, little is known whether it also affects on positive remodeling or not. We investigated the effect of diabetes mellitus on development of positive remodeling.
Method: We investigated consecutive 112 ischemic heart disease patients who had been performed percutaneous coronary interventions (PCI) to mid-LAD (left anterior descending) lesions using IVUS procedure from May 2008 to June 2009 in our hospital. We measured external elastic membrane (EEM) diameter and minimum lumen diameter at the proximal site of LAD, with no significant stenosis. the positive remodeling ratio was determined as follows; EEM diameter∗100/minimum lumen diameter. Patients were assigned into DM or non-DM groups (PG 193.5mg/dl v.s. 124.5mg/dl, respectively).
Results: there was no significant difference in minimum lumen diameter between DM and non-DM groups (3.29+/–0.70v.s.3.50+/–0.75mm, respectively). However, positive remodeling ratio was significantly (p<0.05) grater in DM group (149+/–26%) than in non-DM group (138+/−24%).
Conclusion: It is revealed that the positive remodeling is more advanced in diabetic patients although coronary artery seems to be normal angiographically.
P371
Natriuretic peptides in at risk cohorts: considerations for clinical interpretation
CM Conlon1, C Kelleher1, I Dawkins2, C O Loughlin2, M Ledwidge2, K Mc Donald2
1
University College Dublin, School of Public Health, Physiotherapy & Population Science, Dublin, Ireland, 2St Vincent's University Hospital, Dublin, Ireland
Topic: Biomarkers
the STOP HF Investigators
Background: B-type natriuretic peptide (BNP) has been proffered as a screening tool for echocardiography referral and detection of LVSD. However, despite its excellent sensitivity there are concerns surrounding its poor specificity and the significant issue of false positives. the literature has repeatedly established associates of higher BNP, however, there is a dearth of information on the magnitude of impact of these associates and whether these factors confound BNP expression.
Objective: To identify the principal associates of BNP and examine the extent of association within a population with cardiovascular risk-factors taking cardio-active therapies.
Methodology: We explored the baseline data set of the ongoing Screening to Prevent Heart Failure Study, a prospective study of primary care based individuals with cardiovascular risk-factors and no documented ventricular dysfunction. Univariate and multivariate (logistic regression) models determined associates of BNP. Using sub-set analyses, the foremost associates of BNP were established and the extent to which they were associated with BNP was examined.
Results: Complete data was available in 1122 individuals (mean age 65, 47% Male, 66% Hyper-tension, 49% Hypercholesterolemia, 25% Obesity, 16% Coronary artery disease–49% of whom had myocardial-infarction (MI), 15% Smoking; 11% Diabetes). the most common medications were Statins (63%), Anti-platelet (49%), Beta-blockers (30%), ACE-Inhibitors (28%), AIIA (26%), thiazides (20%), Calcium-Antagonists (16%) and Anti-diabetics (11%). Median biomarker levels fell within normal ranges. Multivariate associates of BNP were age, female, systolic and diastolic blood-pressure, heart-rate, beta-blockers, arrhythmia (all p<.001), calcium-antagonist and MI (all p<0.5).
BNP was examined in the context of age, plotting it against age for each individual. A linear regression line was fitted through Log (BNP) for both gender. Using the age-framework, potential associates of BNP were assessed by plotting the median-BNP by sliding decade of age for those with and without a particular risk-factor (looking for a prominent departure between the lines that persisted with age). In particular, beta-blockers were associated with a 1.7-fold increase in BNP.
Conclusions: In defining cut-offs for BNP screening, at minimum, certain characteristics, comorbidities and therapies must be accounted for. In addition to age-referencing, not accounting for beta-blockers in particular, may in part explain the low specificity associated with BNP screening to date. In research efforts, caution should be taken in using BNP as an end-point in populations on beta-blockers.
P373
Usefulness of natriuretic peptides in primary health care, an explorative study in elderly patients
M Olofsson, K Boman
Research Unit, Department of Medicine and Geriatrics, Skelleftea, Sweden
Topic: Biomarkers
Background: High levels of negative predictive value (NPV) has been shown (95–100%) for younger patients.
Aim: Primarily to explore the (NPV), positive predictive value (PPV), sensitivity and specificity of natriuretic peptides. Secondarily, to evaluate the impact of gender and age in elderly patients with systolic heart failure (HF).
Methods: this is an explorative study from one primary health care centre where 109 patients with symptoms of HF were referred for an echocardiographic examination followed by a cardiovascular consultation. Blood samples for NtproBNP and BNP were collected and stored frozen. Systolic HF was diagnosed in 48 patients (46% men, 54% women, mean age 79 years) while 61 patients (21% men, 79% women, mean age 76 years) had no HF. We explored cut off values for Nt-proBNP from 100 to 500 ng/L partly based on FDA recommendations. To establish corresponding BNP cut-off values we analyzed the quotient between NT-proBNP/BNP in patients with both systolic and diastolic HF who had the highest median levels.
this resulted in cut-off values for BNP from 10 to 50 pg/ml.
Results: Table 1. Shows results of the highest NPV, sensitivity, PPV and specificity for NTproBNP and BNP including all 109 patients. In a linear regression analysis, Nt-proBNP (β= 0,035; p<0,001) and BNP (β= 0,030; p<0,001) were associated with age, but not with gender. In a multivariate analysis age (β= 0,036; p<0,001) and male gender (β=0,270; p=0,014) were associated with Nt-proBNP, while age only significantly associated with increasing levels of BNP (β= 0,030; p<0,001).
Conclusion: Natriuretic peptides in an elderly population showed high NPVs, but not as high as in younger patients with HF in other studies. Age and male gender were associated with higher levels of NT-proBNP while only age was related to BNP.
P372
Can glucose metabolism markers predict post-prandial glycaemia in non-diabetic acute coronary syndrome patients?
S Monteiro, C Lourenco, R Teixeira, E Jorge, R Batista, P Lazaro, P Monteiro, L Providencia
University Hospitals of Coimbra, Coimbra, Portugal
Topic: Biomarkers
Introduction: Glucose metabolism abnormalities are important prognostic predictors in acute coronary syndrome (ACS) patients. Several recent studies have suggested the importance of several glucose metabolism markers and the performance of an oral glucose tolerance test (OGTT) in all non-diabetic ACS patients. However, a question persists: is there a correlation between these markers and post-prandial glycaemia, as assessed by the OGTT?
Aim: To evaluate, in a population of patients not known to be diabetic, admitted for ACS and submitted to OGTT during hospital stay, if there is a relationship between admission glycaemia (AG), glycaemia variation (GV) and glycaemia normalization (GN) and the post-prandial glycaemia determined in the OGTT.
Population and methods: Retrospective analysis of 259 patients not known to be diabetic, admitted for ACS in a single centre and submitted to OGTT during their hospital stay. GV was defined as the difference between AG and the lowest glycaemia value during hospital stay; GN was defined as the difference between AG and the first fasting glycaemia.
Results: After OGTT performance, only 79 patients (30.5%) had a normal glucose metabolism, while 92 (35.5%) showed impaired fasting glucose or impaired glucose tolerance and 88 (34.0%) where diagnosed as diabetics. Patients with an higher post-prandial glycaemia in the OGTT were older, less frequently in Killip class I on admission, had more often high blood pressure, dyslipidaemia, an abnormal ECG and higher heart rate at admission, a diagnosis of myocardial infarction and lower glomerular filtration rate. the spearman correlation test showed that both AG, GV and GN had a positive correlation with higher post-prandial glycaemia values, with the correlation being best for AG (coefficient 0.468; p<0.001) and worst for GN (coefficient 0.281; p<0.001). Multivariate analysis confirmed that all three markers were independent predictors of the post-prandial glycaemia in the OGTT.
Conclusions: In ACS patients without a previous history of diabetes, there is a good correlation between markers of glucose metabolism impairment and post-prandial values of glycaemia determined by OGTT. this fact, never before described, may improve our knowledge of metabolic abnormalities in ACS patients, thus contributing to their better clinical management.
P374
Human growth hormone and IGF-1 in risk stratification of patients with acute myocardial infarction
M Pytliak1, V Vargova1, M Felsoci2, V Mechirova1, A Mandulakova3
1
Safarik University Medical School, Kosice, Slovak Republic, 2Louis Pasteur University Hospital, Kosice, Slovak Republic, 3Hospital in Vranov, nad Toplou, Vranov nad Toplou, Slovak Republic
Topic: Biomarkers
Background: Recently, an increasing number of new biochemical markers has been reported in cardiovascular risk stratification. Clinical risk management of cardiovascular disease would greatly benefit from event stratifying biomarkers. the aim of this study was to compare the concentrations of growth hormone (GH) and insuline like growth factor-1 (IGF-1) in patients with acute myocardial infarction (AMI) hospitalized in intensive care units compared with the control group. Furthermore, authors assessed a possible correlation between the levels of GH and IGF-1 and markers of myocardial necrosis troponin, and a correlation with left ventricular ejection fraction measured on the seventh day after AMI.
Methods: We examined group of 35 patients in the age of 50–60 years with ST segment elevation myocardial infarction (STEMI), defined as clinical manifestations of ischemia, ECG criteria and positivity of cardiospecific enzymes. the control group consisted of 17 patients who were admitted to the hospital for the differential diagnosis of chest pain. these patients had a normal ECG record, negative cardiospecific enzymes, and (if indicated) a negative ergometric examination during hospitalization. For the determination of GH and IGF-1 concentration, blood was collected in peracute phase of 4.5 hours ± 30 minutes after the chest pain had appeared followed by the second specimen on the 7th day after AMI. Echocardiography was performed on the 7-th day of hospitalization.
Results: When compared patients with AMI with control group, their GH levels were significantly higher in peracute phase (1.42 ± 0.25 vs. 0.48 ± 0.07 ng/ml respectively, p<0.001) and nonsignificantly higher on the 7th day after AMI (0.52 ± 0.09 vs. 0.48 ± 0.07 ng/ml respectively). In the group of patients with AMI, GH levels were about 2 to 3-fold higher in peracute stage than on the 7-th day of AIM (1.42 ± 0.25 vs. 0:52 ± 0.09 ng/ml, p<0.01). GH levels correlated positively with troponin levels in peracute phase (r = 0.68159, p = 0.0051) and negatively with the values of ejection fraction measured on the 7th day after AMI (r = −0.733747, p = 0.0018). IGF-1 was positively correlated with left ventricular ejection fraction (r = 0.78741, p = 0.0005).
Conclusion: Based on our data, we suggest that monitoring of the concentration of GH and IGF-1 in peracute phase of AMI might be of clinical importance in risk stratification, early detection of development of left ventricular dysfunction and eventually treatment monitoring.
P375
Heart Fatty Acid Binding Protein (h-FABP) is an optimal point of care diagnostic test in early phase of non-ST elevation Acute Coronary Syndromes
M Rus, MI Popescu, AI Ardelean, C Costescu, EE Babes, VV Babes
University of Medicine and Pharmacy, Oradea, Romania
Topic: Biomarkers
Introduction: the heart-type specific Fatty Acid Binding Protein (h-FABP) is a small, cytosolic protein (15 kDa) which may be useful for both rapid confirmation and exclusion of acute myocardial infarction.
Objective: To determine the usefulness of a qualitative h-FABP rapid test (Cardio Detect-med) in a group of patients with acute coronary syndrome without persistent ST-segment elevation.
Method: In group of 100 (66 males, 34 females; 64 smokers) consecutive patients (mean age 61,66 years; median 62,5 years) with acute coronary syndrome without ST-segment elevation on admission (median onset-to-door interval was 6 hours (range 1 to 24 hours); Ecg exam at admission showed non ST-segment elevation (normal Ecg or ST depression or T wave inversion) and without renal insufficiency and muscle injury.
Qualitative tests for serum h-FABP and quantitative for cardiac troponin I (cut-off value = 0.1çg/L) and CK-MB (cut-off value 24 U/L) were performed on admission and 3 hours later. the ultimate diagnosis of NSTEMI was confirmed in case of a second positive result of cTnI measurement. Each patient uderwent diagnostic coronarography to confirm level of coronary artery stenosis.
Results: NSTEMI was finally diagnosed at 56 pts out of total 100 (56%). Diagnostic sensitivity, specificity, positive, negative predictive value and accuracy on admission and after 3 hour for h-FABP, CK-MB and cTnI are shown on the table.
h-FABP- heart Fatty Acid Binding Protein, CK-MB-fraction MB of creatine kinase, cTnI -cardiac troponin I.
P376
Does uric acid have a pathogenetic role in left ventricular remodelling and arrhythmogenesis in patients after myocardial infarction ?
S Lypovetska, MI Shved
Ternopil State Medical University, Ternopil, Ukraine
Topic: Biomarkers
Background: the role of serum uric acid (SUA) in the process of atherosclerosis and atherotrombosis is controversial. Epidemiological studies have recently shown that SUA may be risk factor for cardiovascular diseases and negative prognostic marker for mortality in subjects after myocardial infarction.
Aim: To investigate the potential impact of SUA levels on left ventricular structural, functional changes and arrhythmogenesis in patients after myocardial infarction.
Methods: 127 patients (59,2±0,8 years old) after myocardial infarction were included in cross-sectional study. the subjects were divided in two groups with high and normal SUA level. Echocardiographic assessment, Holter monitoring were performed.
Results: Patients with high SUA (n=86) compared to those with low SUA (n=41) had higher left ventricular mass 6,9 vs 147,4± index (220,9±0,01) and left atrial dimension (4,0<8,3, p±0,5 vs 3,5±0,8, p<0,01), while did not differ in ejection fraction. Concentric and excentric hypertrophy were observed in 58,1 % and 38,4 % patients with hyperuricemia, 26,8 % and 31,7% - with normouricemia. Diastolic dysfunction was more often investigated in 0,01). SUA levels<pati-patients with high SUA than with normal (94,2 % vs 36,6 %, p correlated significantly with mitral E wave velocity (r=0,61, p<0,01), E wave 0,05). there was no<0,01), E/A ratio (r=0,21, p<decelaration time (r=0,26, p difference in frequency of atrial fibrilation and supraventricular prematures in both groups, while high grade ventricular prematures according to Lown Wolf were observed in 2,5 times more often in patients with high SUA Also they had increased Q-T dispersion more than 70 ms and decreased heart rate variability (SDNN less than 100 ms). Involment of His-Purkinje system was more often observed inpatients with hyperuricemia (74,4 % vs 26,8 %, p<0,01).
Conclusion: Elevated SUA level is associated with left ventricular hypertrophy and diastolic dysfunction in patients after myocardial infarction, reflecting increased cardiovascular risk Left ventricular hypertrophy plays important role in arrhytmogenesis and along with hyperuricemia it is a strong risk factor for future cardiac events as well as sudden cardiac death.
P377
Serial measurements of NT-proBNP in with unstable angina pectoris treated by statins
A Astvatsatryan, M Senan
European Regional Educational Academy, Faculty of Medicine, Yerevan, Armenia
Topic: Biomarkers
It is well known that brain natriuretic peptide (BNP) and N-terminal fragment (NT-proBNP) levels in the blood are used for screening, diagnosis of acute congestive heart failure (CHF) and may be useful to establish prognosis in heart failure, as both markers are typically higher in patients with worse outcome. the plasma concentrations of both BNP and NT-proBNP are also typically increased in patients with asymptomatic or symptomatic left ventricular dysfunction. there is no strict level of BNP that perfectly separates patients with and without heart failure. there are limited data on evolution of BNP/NTproBNP levels in unstable angina pectoris (UA). HMG-CoA reductase inhibitors (statins) substantially improve clinical outcomes in pts with CAD. therefore, we tried to assess the clinical significance of serial measurements of serum NT-proBNP in UA treated with different types of statins (Pravastatin and Atorvastatin).
Methods: 42 pts (14 female, aged 46±21) with UA were involved in our study with follow up 20 weeks. In 24 hours after admission pts were randomized on Pravastatin (P) 80 mg/daily (Group P, n=20) or Atorvastatin 40 mg/daily (Group A, n=22). All pts were on standard therapy (heparin, aspirin, beta-blockers, nitrates, 33 were on ACE inhibitors). Total cholesterol (TCL) was measured on admission and on 20 week On 12 hrs and 24 hrs after admission blood samples were collected for NT-proBNP.
Results: Serum NT-proBNP concentration was higher in Group P 1969 pg/ml [75–44775] than in Group A 12339 pg/ml [776–41667], (p<0.03) after 12 hour and 1037 pg/ml [96–32345] vs. 11930 pg/ml [105–65022], p<0.01 after 24h. Unexpectedly, in the Group A NT-proBNP decreased during first week of the treatment (p<0,001), while in Group P NT-proBNP remained at the same high level. the primary end-point (a composite end-point of death, non-fatal MI, rehospitalization for worsening angina at 20 weeks) was better in Group A: 13.8% vs. 18.54% (p < 0.05) but robust£ endpoints like death/MI were similar in both groups (11.2% vs. 11.9%; p=NS). the difference in the primary end-point was driven by rehospitalization for recurrent angina (6.3% vs. 8.9%). During all follow up, TCL drops more significantly in Group A. On the end of follow up TCL became normal in 10 pts (49.9%) in Group P and 16 (72.7%) in Group A (p<0.03) without significant hepatic enzyme elevations.
Conclusion: Near normal NT-proBNP values or their rapid decrease within first 24 hrs of the treatment of UA, indicate good prognosis, while persistent elevated NT-proBNP during treatment suggests high-risk pts. A seems to be more preferable than P in pts with UA.
P378
Absorption and filtration apheresis columns lower LDL equally, but have different effects on inflammatory biomarkers
A Hovland, RI Hardersen, TE Mollnes, KT Lappegard
Nordland Hospital, Bodo, Norway
Topic: Biomarkers
Purpose: Low density lipoprotein (LDL) apheresis is well established in hypercholesterolemia otherwise uncontrolled. this treatment affects biomarkers of importance in atherosclerosis. Hence we systematically compared three different LDL apheresis columns in this regard.
Methods: three patients with heterozygous familial hypercholesterolemia participated in a cross-over study with six concurrent treatments with three different LDL apheresis columns: DL75 (whole blood adsorption), LA15 (plasma adsorption) and EC50W (plasma filtration). Blood samples were drawn before and after treatment. A range of biochemical parameters and inflammatory biomarkers, including LDL-cholesterol, high-sensitivity C Reactive Protein (hs-CRP) and numerous cytokines, were compared. Due to inter-individual variation, cytokine concentrations were normalized for evaluation of column effect.
Results: All three columns gave a 66–69% decrease in LDL. the reduction was highly significant (p<0.001) without inter-column differences. Hs-CRP dropped 75%, 69% and 46% for columns DL75, LA15 and EC50W, respectively (p<0.001 for all). Normalized changes in cytokines are shown in the table below. Of notice is the considerable increase in IL-1ra and IP-10 with the whole blood column DL75, and the decrease in TNF-α and VEGF with the adsorptive columns DL75 and LA15. Other cytokines, including IL-6, showed less change. the column EC50W induced a 13.3 fold increase in the anaphylatoxin C3a but left C5a-levels unchanged. the other two columns gave a modest increase in C3a and a reduction in C5a.
Conclusions: the LDL-apheresis columns DL75, LA15 and EC50W all lowered LDL-cholesterol significantly and to the same extent. Hs-CRP was also significantly reduced. However, several cytokines with importance for coronary atherosclerosis including IL-1ra, IP-10, MCP-1 and TNF-α were differently affected by the columns, as were the anaphylatoxins C3a and C5a. this should be kept in mind in LDL-apheresis, as these patients are at high risk for atherosclerotic events.
Normalized mean values of selected biomarkers after LDL apheresis with three different columns. Pretreatment value = 1, n=18, p<0.05.
