Cardiovascular reactivity to mental stress test, autonomic balance and baroreflex sensitivity in hypertensive patients

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Grover

~ - 1 ] CAN DISCUSSING A PATIENT'S CALCULATED CORONARY RISK INCREASE THE EFFECTIVENESS OF DYSLIPIDEMIA THERAPY? PRELIMINARY RESULTS OF THE CHECK-UP STUDY S.A. Grover, I. Lowensteyn, L. Coupal, S. Marchand, M. Kaouache, C. Brewer. The Montreal General Hospital, Montreal, Quebec, Canada Objectives: Current international lipid guidelines recommend treating dyslipidemia after calculating each patient' s coronary risk. We randomized patients to receive printed risk profiles (RP) based on Framingham data before and after initiating lipid treatment or usual care (UC) to determine if ongoing feedback would improve patient compliance with lifestyle modification and statin therapy (based on current Canadian guidelines). Methods: Patients age 30 70, were eligible for statin treatment (specific drug chosen by the physician) if they had known cardiovascular disease, diabetes, or a 10-year coronary risk >30% with LDL/>2.5mmol/L or total cholesterol (TC)/HDL/>4; 20 30% risk with LDL/>3or TC/HDL/>5. Those with 1020% risk and LDL/>4 or TC/HDL/>6 could receive 3 months of dietary modification and exercise to reach these targets before starting statins. Lipid profiles were completed before randomization and after 3 months to document the change in blood lipids following treatment. Results: Baseline lipids and other risk factors were similar among 537 RP and 553 UC patients. Among 107 patients trying lifestyle modification, RP patients were significantly (p-0.02) more likely to reach lipid targets (39% vs 18%). Among 983 statin treated patients, there were significantly (p~<0.01) greater reductions in TC, LDL, and TC/HDL among RP patients (26% vs 23%, 34% vs 31%, and 26% vs 23%). Conclusions: Ongoing RP feedback doubles the success rate in reaching lipid targets after lifestyle modification and increases the effectiveness of statin therapy. Further follow-up will evaluate the long-term impact of RP on blood lipids and coronary risk and identify possible explanations for the observed effect. ~ 4 - ~ REACHING LIPID TARGETS FOLLOWING STARTING DOSES OF STATINS IN PRIMARY CARE: THE RESULTS OF THE CHECK-UP STUDY S.A. Grover, I. Lowensteyn, M. Kaouache, S. Marchand, L. Coupal, C. Brewer. The Montreal General Hospital, Montreal, Quebec, Canada Objectives: Many dyslipidemia patients do not reach recommended targets. We randomized patients to receive printed risk profiles (RP) based on Framingham data before initiating lipid treatment or usual care (UC) to determine if knowing their calculated coronary risk would improve patient compliance. We also evaluated the effectiveness of statin therapy as selected by 171 family physicians. Methods: Patients age 30~0, were eligible for treatment if they had known cardiovascular disease, diabetes, or a 10-year coronary risk>30% with LDL/>2.5mmol/L or total cholesterol (TC)/HDL />4; 2 0 0 0 % risk with LDL/>3 or TC/HDL/>5, or 1020% risk and LDL/>4 or TC/HDL/>6. (Canadian guidelines). Lipid profiles were completed before randomization and after 3 months to document which patients reached the above targets. Using logistic regression analyses we also compared specific statins after adjustment for baseline lipids and RP vs UC. Results: Among 983 patients, 750 (76%) received atorvastatin, 142 (14%) simvastatin, 46 (5%) pravastatin and 45 (5%) other statins. Overall, 62% of patients reached LDL targets, 61% TC/HDL targets, and 48% both targets. Atorvastatin treated patients were significantly (p<0.05) more likely to reach LDL and TC/HDL targets (67%, 65%) than patients treated with simvastatin (51%, 53%), pravastatin (37%, 41%), or other statins (43%, 36%). Simvastatin patients also reached each target more than pravastatin patients (p<0.05). Conclusions: Following 3 months of statins selected by physicians, 52% of patients did not reach both lipid targets. Follow-up over 12 months will determine if physicians do successfully titrate treatment to target. ~ - 3 ] CARDIOVASCULAR REACTIVITY TO MENTAL STRESS TEST, AUTONOMIC BALANCE AND BAROREFLEX SENSITIVITY IN HYPERTENSIVE PATIENTS L. Guasti 1, D. Zanotta 1, L.T. Mainardi 2, C. Simoni 1, D. Garganico 1, C. Crespi 1, G. Gaudio 1, A. Maffiolini 1, A.M. Grandi 1, S. Cerutti 2, A. Venco 1. JInternal Medicine, University of Insubria, Varese,"2Department

of Biomedical Engineering, Polytechnic University, Milano, Italy Increased reactivity to various stress tests has been associated with increased morbility in hypertension. The aim of this study was to investigate whether

baseline indexes of simpathovagal balance or baroreflex sensitivity (LFalphaindex) were correlated with heart rate or arterial pressure reactivity to arithmetic mental stress test (AMST). Thirty-four hypertensive, otherwise healthy male subjects ( 3 0 3 0 years) were studied in the morning, without any pharmacological treatment. The AMST was performed during continuous monitoring of electrocardiographic and blood pressure signals. Spectral parameters of RR variability (RRvar: LF/HF ratio, LF normalized units -nu-, HFnu), and a baroreflex sensitivity index (LFalpha-index, cross-spectrum analysis) were calculated at rest, during the test 5 ~ and during recovery 10q The stress test induced a reduction of mean RR (deltaRR: difference between stress value - baseline value: -114±82 ms) and an increase of mean systolic blood pressure (deltaSBP: difference between stress value baseline value: 27±15 mmHg). The LF/HF ratio increased during the test and returned towards baseline values in the recovery (ANOVA for repeated measures: p-.018) whereas the LFalpha-index decreased during the stress test and increased in the recovery phase (p-.009). The deltaRR and the deltaSBP were not correlated with either baseline RRvar or LFalpha-index. In conclusion, baseline indexes of simpathovagal balance and baroreflex sensitivity may not account for changes in haemodynamic variables induced by stress test. Thus, cardiovascular reactivity which follows central stimuli during mental stress is independent from baseline autonomic function and baroreflex sensitivity in hypertensive patients. ~ 4 - ~ REDUCTION OF POSTPRANDIAL ACCUMULATION AND CETP-MEDIATED REMODELLING OF TRIGLYCERIDE-RICH LIPOPROTEIN SUBSPECIES BY ATORVASTATIN IN TYPE IIB HYPERLIPIDEMIA M. Guerin 1, P. Egger 1, W. Le Goff1, C. Soudant 1, R. Dupuis2, M.J. Chapman 1. llnserm U551," 2Pfizer, Paris, France Postprandial triglyceride-rich lipoproteins (TRL) exert direct atherogenic effects at the arterial wall. The effect of atorvastatin, at a daily dose of 40 mg, on the evolution of TRL subspecies and on CETP activity in subjects (n-11) displaying atherogenic Type IIB hyperlipidemia was evaluated following consumption of a mixed meal (1200 kcal; 14% protein, 38% carbohydrate and 48% fat). During postprandial lipemia, the area under the curve (AUC) for plasma triglycerides (-48%; p<0.01), chylomicrons, Sf>400 (-30%; p<0.03), VLDL-1, Sf 6 0 4 0 0 (-51%; p<0.0005) and VLDL-2, Sf 20 60 (-46%; p<0.0005) were significantly reduced by atorvastatin therapy. The postprandial incremental in AUC (iAUC) above baseline concentrations was significantly decreased for plasma triglyceride (-55%; p<0.01), chylomicrons (-40%; p<0.03) and VLDL-1 (-52%; p<0.02). Before atorvastatin therapy, postprandial cholesteryl ester mass transfer from HDL to chylomicrons and VLDL-1 was preferentially stimulated (2.5-fold and 1.8fold respectively) at 4 hours; such changes occurred concomitantly with elevation in mass and particle number of both chylomicrons and VLDL-1. By contrast, following atorvastatin therapy, marked reduction in numbers of apoB-containing particle acceptors led to a marked decrease in both fasting and postprandial CE transfer from HDL to VLDL-1 (-32%; p<0.05). We conclude that atorvastatin mediates not only enhanced catabolism but also diminished production of TRL, which primarily include chylomicrons, chylomicron remnants and VLDL-1, during postprandial lipemia in Type IIB hyperlipidemia. Atorvastatin normalised CETP-mediated CE mass transfer to atherogenic TRL. Therefore atorvastatin acts to significantly reduce the postprandial atherosclerotic burden in the atherogenic IIB dyslipidemic phenotype. ~-~

DOSE-DEPENDENT ACTION OF ATORVASTATIN ON CETP ACTIVITY, ATHEROGENIC apoB-CONTAINING LIPOPROTEINS AND CELLULAR FREE CHOLESTEROL EFFLUX IN TYPE IIB HYPERLIPIDEMIA

M. Guerin 1, R Egger 1, W. Le Goff1, C. Soudant 1, A. Van Tol 2 , R. Dupuis3, M.J. Chapman 1. I INSERM U551, Paris, France," 2Erasmus University,

Rotterdam, The Netherlands," 3Pfizer, Paris, France The dose-dependent and independent effects of atorvastatin, (10 mg and 40 mg) were evaluated on triglyceride-rich lipoprotein (TRL) subclasses, on the major LDL subclasses, on plasma lipid transfer protein activities and on plasma-mediated cellular cholesterol efflux in patients (n-10) displaying Type IIB hyperlipidemia. Plasma concentrations of TRL subclasses and of LDL were markedly diminished after 6 weeks of statin treatment at 10 mg/d (-31% and -36%, respectively p<0.002) and by 42% and by 51% respectively at the 40 mg/d dose. Dense LDL levels were reduced by up

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