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Effects of treatment on endothelial function, angiogenesis and thrombogenesis in hypertension
2A
ORALS: Assessment of Cardiovascular Risk: Why and How?
OR-4 WHO SHOULD HAVE THEIR CHOLESTEROL MEASURED? A COMPARISON OF SELECTIVE CHOLESTEROL SCREENING METHODS Sarah Wilson, Atholl Johnston, John Robson, Neil Poulter, David Collier, Gene Feder, Mark Caulfield. Clinical Pharmacology, Barts and The London, London, United Kingdom; General Practice and Primary Care, Barts and The London, London, United Kingdom; Clinical Pharmacology, Imperial College, London, United Kingdom. The purpose of this study was to compare three methods for identifying high risk individuals for cholesterol measurement. This targets resources to those at greatest risk of future heart disease. A cohort of 3450 individuals from the 1998 Health Survey for England with no record of coronary heart disease, hypertension, diabetes or a family history of premature coronary disease was defined [1]. Each individuals 10 year coronary heart disease risk was calculated from the Framingham equation using measured cholesterol values [2]. Recommendations for selective cholesterol measurement were determined using the Sheffield Tables, different age thresholds or by calculating 10 year coronary heart disease risk using estimated cholesterol values [3,4]. Cholesterol measurement was considered necessary in those individuals whose risk exceeded 15% over 10 years. The optimal value for each test was defined as the maximum sum of the sensitivity and specificity. To identify all those at greater than 15% risk the Sheffield Tables recommended cholesterol measurement in 62% of this population. This gives a sensitivity of 100% (95% Confidence Interval, 98 to 100) but a specificity of 41% (95% CI, 39-42). Using a threshold of 50 years required cholesterol measurement in 31% of this population to identify 88% of those at greater than 15% risk. This gives a sensitivity of 88% (95% CI, 84-93) and a specificity of 73% (95% CI, 71-74). The sum of sensitivity and specificity was maximised using an average total to high density lipoprotein cholesterol ratio of 7 in the Framingham risk equation. This required screening 16% of this population to identify 92% of those at greater than 15% risk. This gives a sensitivity of 92% (95% CI, 88-96) and a specificity of 89% (95% CI, 88-90). In this population using an estimated total to high density lipoprotein cholesterol ratio of 7 and screening on the basis of an estimated 10 year coronary risk of 15% or more had the highest specificity and reduced the number of cholesterol measurements in low risk individuals. Although there was a reduction in sensitivity using this method all individuals with a risk of 30% or more were identified for actual cholesterol measurement. This method of selective cholesterol screening may help clinicians to target investigations and treatment to those at greatest risk of future coronary heart disease. [1]HSE 1998, The Stationery Office, Department of Health [2]Anderson KM et al. Circulation 1991; 83: 356-62 [3]Ramsay LE et al. Journal Human Hypertension 1999;13: 569-592 [4]Robson et al. British Medical Journal 2000; 320:702-704 Key Words: Guidelines, Cholesterol Screening, Coronary Heart Disease Risk
OR-5 DO THE SPECIALISTS STRATIFY THE CARDIOVASCULAR RISK BETTER THAN GENERAL PRACTITIONERS? Vivencio Barrios, Josefa Navarro-Cid, Alberto Caldero´n, Carlos Campo, Luis M. Ruilope. Cardiology, Hospital Ramo´n y Cajal, Madrid, Madrid, Spain; Hypertension Unit, Hospital 12 de Octubre, Madrid, Madrid, Spain. The CONTROLRISK study was aimed to know the cardiovascular risk (CVR) profile of the Spanish hypertensive patients attended in primary care medicine (PCM) and compared it to that of the patients who attend a specialist outpatient clinic (SOC). We investigated whether the spe0895-7061/02/$22.00
AJH–April 2002–VOL. 15, NO. 4, PART 2
cialists stratified the CVR better than general practitioners (GPs). For this purpose, with the clinical data provided by the physicians, we centrally classified the CVR level and compared it with the CVR assessed by the physician. For reminding the risk stratification, we gave to all the investigators (from SOC and PCM) the WHO/ISH 1999 table. We present the preliminary data of the first enrolled patients. To date, 6.858 patients have been included, 3.694 from SOC and 3.164 from PCM. The demographic characteristics are: age 63.1⫾11 vs 63.3⫾11 (SOC vs PCM; p⫽ns); females 52.1% vs 56.6% (p⬍0.05); BMI 28.5⫾4.5 vs 29⫾4.8 kg/m2 (p⫽ns). Systolic blood pressure (BP) was higher in the SOC patients: 160.5⫾16 vs 159.5⫾16 (p⫽0.017). However, diastolic BP was similar in both groups: 93.1⫾10 vs 92.7⫾10. When the CVR assessed by the core lab was compared to that considered by the physicians we observed significant differences in both PCM and SOC. In PCM, although 54% of the patients were actually of high or very high risk (30% very high), the physicians considered high/very high risk only in 42% (13% very high). The investigator correctly classified the CVR in 47% of low risk patients, 68% of medium risk, 54% of high risk and 35% of very high risk patients. In SOC, 71% were high/very high risk patients (38% very high), but the physicians identified high/very high risk in only 52% (18% very high). The classification performed by the physician was correct in 43.5% of low risk patients, 63.5% of medium risk, 55% of high risk and 18% of very high risk patients. Conclusions. Despite the documentation to remind CVR stratification was provided, the GPs as well as the specialists tend to underestimate the CRV of hypertensive population. The rate of very high risk patients who were correctly classified was even lower for the group of specialists than for the group of GPs (18% vs 35%). These data suggest that CVR stratification is not better performed in SOC than in PCM, moreover it seems to be even worse in SOC Key Words: Cardiovascular Risk Stratification, Primary Care Medicine, Specalists
OR-6 EFFECTS OF TREATMENT ON ENDOTHELIAL FUNCTION, ANGIOGENESIS AND THROMBOGENESIS IN HYPERTENSION Dirk C. Felmeden, Charles C.G. Spencer, Natali A.Y. Chung, Andrew D. Blann, Gregory Y.H. Lip, Gareth D. Beevers. University Department of Medicine, City Hospital NHS Trust, Birmingham, United Kingdom. Hypertensive patients are at particular risk of cardiovascular complications, related to endothelial dysfunction, thrombogenesis, and possibly abnormal angiogenesis. These processes can be assessed by flow-mediated dilatation (FMD), plasma levels of von Willebrand Factor (vWF) [as indices of endothelial dysfunction], tissue factor (TF, an index of thrombogenesis), vascular endothelial growth factor (VEGF) and its soluble receptor, sFlt-1 [indices of angiogenesis]. We assessed endothelial function, thrombogenesis and angiogenesis in 76 patients with hypertension (71 males; mean age 64; mean blood pressure 167/72 mm Hg) and additional risk factors, and related them to patients cardiovascular (CHD) and cerebrovascular (CVA) risk, using the Framingham equation. Patients were compared with 48 healthy controls. In hypertensives, the effects of 6 months intensified blood pressure (BP) and (where appropriate) lipid-lowering treatment were investigated. In the hypertensive patients, plasma TF, VEGF and vWf levels were higher, but sFlt-1 levels and FMD were lower (all p⬍0.001) compared with the controls. TF correlated positively with systolic and diastolic blood pressure, as well as 10-year CHD risk and CVA risk scores (all p⬍0.001), and negatively with FMD (p⬍0.001). Following treatment, total cholesterol, blood pressure, levels of TF, VEGF and vWf all fell, whereas FMD and sFlt-1 increased (all p⬍0.001). Plasma levels of TF correlated positively with VEGF (Spearman, r⫽0.640, p⬍0.001) and © 2002 by the American Journal of Hypertension, Ltd. Published by Elsevier Science Inc.
AJH–April 2002–VOL. 15, NO. 4, PART 2
ORALS: Assessment of Cardiovascular Risk: Why and How?
vWf (r⫽0.382,p⬍0.001), with a negative correlation between TF levels and FMD (r⫽-0.578,p⬍0.001). In hypertension, the processes of thrombogenesis, endothelial function and angiogenesis are abnormal, and correlate with overall cardiovascular risk and with each other. Indices of endothelial dysfunction, thrombogenesis and angiogenesis are beneficially affected by intensive BP/lipid treatment. Key Words: Thrombogenesis-Tissue Factor, Angiogenesis-VEGF, Endothelial Function-FMD
tot. Chol [mmol/l] HDL [mmol/l] SBP [mmHg] DBP [mmHg] FMD [%] TF [pg/ml] VEGF [pg/ml] sFlt-1 [ng/ml] vWF [IU/dl]
3A
Baseline
after 6 months treatment
p-value
5.8 (1.0) 1.3 (0.4) 167 (15) 92 (11) 4.8 (1.3) 83 (41–210) 400 (210–1450) 4.3 (1.7–20) 138 (28)
5.3 (1.3) 1.3 (0.4) 144 (13) 83 (10) 7.3 (1.7) 65 (25–130) 270 (180–1050) 6 (2.2–20) 129 (33)
<0.001 0.316 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001
ORALS: Assessment of Cardiovascular Risk: Why and How?
OR-4 WHO SHOULD HAVE THEIR CHOLESTEROL MEASURED? A COMPARISON OF SELECTIVE CHOLESTEROL SCREENING METHODS Sarah Wilson, Atholl Johnston, John Robson, Neil Poulter, David Collier, Gene Feder, Mark Caulfield. Clinical Pharmacology, Barts and The London, London, United Kingdom; General Practice and Primary Care, Barts and The London, London, United Kingdom; Clinical Pharmacology, Imperial College, London, United Kingdom. The purpose of this study was to compare three methods for identifying high risk individuals for cholesterol measurement. This targets resources to those at greatest risk of future heart disease. A cohort of 3450 individuals from the 1998 Health Survey for England with no record of coronary heart disease, hypertension, diabetes or a family history of premature coronary disease was defined [1]. Each individuals 10 year coronary heart disease risk was calculated from the Framingham equation using measured cholesterol values [2]. Recommendations for selective cholesterol measurement were determined using the Sheffield Tables, different age thresholds or by calculating 10 year coronary heart disease risk using estimated cholesterol values [3,4]. Cholesterol measurement was considered necessary in those individuals whose risk exceeded 15% over 10 years. The optimal value for each test was defined as the maximum sum of the sensitivity and specificity. To identify all those at greater than 15% risk the Sheffield Tables recommended cholesterol measurement in 62% of this population. This gives a sensitivity of 100% (95% Confidence Interval, 98 to 100) but a specificity of 41% (95% CI, 39-42). Using a threshold of 50 years required cholesterol measurement in 31% of this population to identify 88% of those at greater than 15% risk. This gives a sensitivity of 88% (95% CI, 84-93) and a specificity of 73% (95% CI, 71-74). The sum of sensitivity and specificity was maximised using an average total to high density lipoprotein cholesterol ratio of 7 in the Framingham risk equation. This required screening 16% of this population to identify 92% of those at greater than 15% risk. This gives a sensitivity of 92% (95% CI, 88-96) and a specificity of 89% (95% CI, 88-90). In this population using an estimated total to high density lipoprotein cholesterol ratio of 7 and screening on the basis of an estimated 10 year coronary risk of 15% or more had the highest specificity and reduced the number of cholesterol measurements in low risk individuals. Although there was a reduction in sensitivity using this method all individuals with a risk of 30% or more were identified for actual cholesterol measurement. This method of selective cholesterol screening may help clinicians to target investigations and treatment to those at greatest risk of future coronary heart disease. [1]HSE 1998, The Stationery Office, Department of Health [2]Anderson KM et al. Circulation 1991; 83: 356-62 [3]Ramsay LE et al. Journal Human Hypertension 1999;13: 569-592 [4]Robson et al. British Medical Journal 2000; 320:702-704 Key Words: Guidelines, Cholesterol Screening, Coronary Heart Disease Risk
OR-5 DO THE SPECIALISTS STRATIFY THE CARDIOVASCULAR RISK BETTER THAN GENERAL PRACTITIONERS? Vivencio Barrios, Josefa Navarro-Cid, Alberto Caldero´n, Carlos Campo, Luis M. Ruilope. Cardiology, Hospital Ramo´n y Cajal, Madrid, Madrid, Spain; Hypertension Unit, Hospital 12 de Octubre, Madrid, Madrid, Spain. The CONTROLRISK study was aimed to know the cardiovascular risk (CVR) profile of the Spanish hypertensive patients attended in primary care medicine (PCM) and compared it to that of the patients who attend a specialist outpatient clinic (SOC). We investigated whether the spe0895-7061/02/$22.00
AJH–April 2002–VOL. 15, NO. 4, PART 2
cialists stratified the CVR better than general practitioners (GPs). For this purpose, with the clinical data provided by the physicians, we centrally classified the CVR level and compared it with the CVR assessed by the physician. For reminding the risk stratification, we gave to all the investigators (from SOC and PCM) the WHO/ISH 1999 table. We present the preliminary data of the first enrolled patients. To date, 6.858 patients have been included, 3.694 from SOC and 3.164 from PCM. The demographic characteristics are: age 63.1⫾11 vs 63.3⫾11 (SOC vs PCM; p⫽ns); females 52.1% vs 56.6% (p⬍0.05); BMI 28.5⫾4.5 vs 29⫾4.8 kg/m2 (p⫽ns). Systolic blood pressure (BP) was higher in the SOC patients: 160.5⫾16 vs 159.5⫾16 (p⫽0.017). However, diastolic BP was similar in both groups: 93.1⫾10 vs 92.7⫾10. When the CVR assessed by the core lab was compared to that considered by the physicians we observed significant differences in both PCM and SOC. In PCM, although 54% of the patients were actually of high or very high risk (30% very high), the physicians considered high/very high risk only in 42% (13% very high). The investigator correctly classified the CVR in 47% of low risk patients, 68% of medium risk, 54% of high risk and 35% of very high risk patients. In SOC, 71% were high/very high risk patients (38% very high), but the physicians identified high/very high risk in only 52% (18% very high). The classification performed by the physician was correct in 43.5% of low risk patients, 63.5% of medium risk, 55% of high risk and 18% of very high risk patients. Conclusions. Despite the documentation to remind CVR stratification was provided, the GPs as well as the specialists tend to underestimate the CRV of hypertensive population. The rate of very high risk patients who were correctly classified was even lower for the group of specialists than for the group of GPs (18% vs 35%). These data suggest that CVR stratification is not better performed in SOC than in PCM, moreover it seems to be even worse in SOC Key Words: Cardiovascular Risk Stratification, Primary Care Medicine, Specalists
OR-6 EFFECTS OF TREATMENT ON ENDOTHELIAL FUNCTION, ANGIOGENESIS AND THROMBOGENESIS IN HYPERTENSION Dirk C. Felmeden, Charles C.G. Spencer, Natali A.Y. Chung, Andrew D. Blann, Gregory Y.H. Lip, Gareth D. Beevers. University Department of Medicine, City Hospital NHS Trust, Birmingham, United Kingdom. Hypertensive patients are at particular risk of cardiovascular complications, related to endothelial dysfunction, thrombogenesis, and possibly abnormal angiogenesis. These processes can be assessed by flow-mediated dilatation (FMD), plasma levels of von Willebrand Factor (vWF) [as indices of endothelial dysfunction], tissue factor (TF, an index of thrombogenesis), vascular endothelial growth factor (VEGF) and its soluble receptor, sFlt-1 [indices of angiogenesis]. We assessed endothelial function, thrombogenesis and angiogenesis in 76 patients with hypertension (71 males; mean age 64; mean blood pressure 167/72 mm Hg) and additional risk factors, and related them to patients cardiovascular (CHD) and cerebrovascular (CVA) risk, using the Framingham equation. Patients were compared with 48 healthy controls. In hypertensives, the effects of 6 months intensified blood pressure (BP) and (where appropriate) lipid-lowering treatment were investigated. In the hypertensive patients, plasma TF, VEGF and vWf levels were higher, but sFlt-1 levels and FMD were lower (all p⬍0.001) compared with the controls. TF correlated positively with systolic and diastolic blood pressure, as well as 10-year CHD risk and CVA risk scores (all p⬍0.001), and negatively with FMD (p⬍0.001). Following treatment, total cholesterol, blood pressure, levels of TF, VEGF and vWf all fell, whereas FMD and sFlt-1 increased (all p⬍0.001). Plasma levels of TF correlated positively with VEGF (Spearman, r⫽0.640, p⬍0.001) and © 2002 by the American Journal of Hypertension, Ltd. Published by Elsevier Science Inc.
AJH–April 2002–VOL. 15, NO. 4, PART 2
ORALS: Assessment of Cardiovascular Risk: Why and How?
vWf (r⫽0.382,p⬍0.001), with a negative correlation between TF levels and FMD (r⫽-0.578,p⬍0.001). In hypertension, the processes of thrombogenesis, endothelial function and angiogenesis are abnormal, and correlate with overall cardiovascular risk and with each other. Indices of endothelial dysfunction, thrombogenesis and angiogenesis are beneficially affected by intensive BP/lipid treatment. Key Words: Thrombogenesis-Tissue Factor, Angiogenesis-VEGF, Endothelial Function-FMD
tot. Chol [mmol/l] HDL [mmol/l] SBP [mmHg] DBP [mmHg] FMD [%] TF [pg/ml] VEGF [pg/ml] sFlt-1 [ng/ml] vWF [IU/dl]
3A
Baseline
after 6 months treatment
p-value
5.8 (1.0) 1.3 (0.4) 167 (15) 92 (11) 4.8 (1.3) 83 (41–210) 400 (210–1450) 4.3 (1.7–20) 138 (28)
5.3 (1.3) 1.3 (0.4) 144 (13) 83 (10) 7.3 (1.7) 65 (25–130) 270 (180–1050) 6 (2.2–20) 129 (33)
<0.001 0.316 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001