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5: Hypertension and stroke
Multiple Risk Factors in Cardiovascular Disease—Abstracts
Funding: The studies presented are supported by grants from the Netherlands Heart Foundation and the Dutch Diabetes Research Foundation
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Risk assessment for cardiovascular disease is primarily carried out as a guide to drug treatment. Because of the high cost of drugs, it has been necessary to do short-term (5-10 year) risk assessment to determine whether a particular drug treatment is cost-effective. This was particularly true of statins drugs which were patent-protected and quite expensive. More recently, since statins have gone off patent, there is a need for how do risk assessment as a guide to drug treatment. Generic statin therapy costs only about one-tenth the costs of patented-statin treatment. Further, aspirin therapy is inexpensive as well. Thus, the two major prevention drugs--statins and aspirin--are generic and cost-effectiveness is no longer an issue. The major issues then become safety and adherence. Selection of patients for drug therapy thus still is important, and identifying patients at lifetime risk for cardiovascular disease becomes more important. For this reason, it can be expected that much of the focus in risk assessment will shift from short-term risk to long-term risk. New modalities for lifetime risk assessment are needed.
A NEW TARGET FOR PREVENTION: INFLUENZA AS A TRIGGER OF ACUTE CORONARY SYNDROMES M. Madjid1,2, S.W. Casscells3. 1Texas Heart Institute Houston, TX, USA, 2 Baylor College of Medicine Houston, TX, USA, 3US Dept of Defense Washington, DC, USA Influenza in a preventable trigger of acute coronary syndromes. Influenza epidemics are almost always associated with sharp increases in cardiovascular events. Multiple studies have shown that influenza vaccination is associated with a remarkable reduction in risk of multiple cardiovascular endpoints including secondary MI, sudden cardiac arrest, stroke, composite interventional endpoints and hospitalization for cardiac causes. Influenza triggers acute coronary syndromes by destabilizing the already-present atherosclerotic vulnerable plaques. Influenza infection in apo E-deficient mice causes platelet aggregation, a marked increase in inflammatory cells in atherosclerotic plaques, and synergistic local and systemic inflammation. Influenza infection also increases the pro-thrombotic tendency. These data suggest an important role for influenza in development of acute cardiovascular events and a cardioprotective role for influenza vaccine. American Heart Association (AHA) and American College of Cardiology (ACC) have recently included influenza vaccination in their secondary prevention guidelines. However, the use of influenza vaccine in cardiac patients is still below the optimum level (about 50% in US). Influenza vaccination needs to be included in the cardiology prevention practice guidelines. Vaccination rate in patients with cardiovascular disease (CVD) needs to be improved. Clinical trials are needed to identify other high risk groups who may additionally benefit from influenza vaccination or use of antiviral agents for CVD prevention. Funding: US DoD T5 grant # W81XWH-04-20035
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WHAT IS CHANGING? SHORT-TERM VS. LONG-TERM RISK S. Grundy. University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA
Funding: none 5 HYPERTENSION AND STROKE G. Mancia. University of Milan-Bicocca, Milan, Italy This presentation will first summarize the epidemiological evidence that hypertension is a major risk factor for stroke, blood pressure values in excess of 115 mmHg systolic accounting for about two thirds of the stroke prevalence worldwide. It will then show that the hypertensionrelated risk of stroke is not irreversible because of the evidence obtained in randomized trials that when blood pressure is reduced by treatment the incidence of stroke can be markedly reduced. Few additional points will finally be presented. One, that in order to optimize protection against stroke in the hypertensive population at large BP should be reduced below 140/90 mmHg but that target
Journal of Clinical Lipidology, Vol 2, No 5S, October 2008
values 130/80 mmHg should be pursued in patients at high cardiovascular risk (diabetics and patients with a history of cardiovascular or renal disease) in whom treatment should be started already in the high normal BP range. Two, similar threshold and target BP values should be adopted for secondary prevention of stroke. Three, evidence that some antihypertensive drug classes possess blood pressure-independent specific cerebrovascular protective properties is at present not conclusive, the major protective role being apparently played by BP control which should be assessed also by out-of-office BP measurements. Four, the blood pressure-related protection can nevertheless be increased by complementary types of treatment such as those leading to lipid control, antiplatelet aggregation and prevention of atrial fibrillation. Finally, data will be presented that antihypertensive treatment can prevent stroke also in patients aged 80 years or more. Funding: none
6 THE USE OF A DIETARY PORTFOLIO APPROACH IN HYPERLIPIDIEMIA D.J.A. Jenkins, T.H. Nguyen, C.W.C. Kendall, J.M.W. Wong, A.R. Josse, N. Fozdar, A. Marchie, R.G. Josse, L.A. Leiter, W. Singer. St. Michael's Hospital and University of Toronto, Toronto, Canada Background: Major advances have been made in the pharmacological control of serum lipids and by comparison little use has been made of dietary components largely because individually the reductions in LDL-C are relatively small. ATP III recommended the use of viscous fiber and plant sterols to strengthen the diet effect and the FDA have added soy protein and nuts for which cholesterol lowering health claims can be made. Theoretically, if a low saturated fat, low cholesterol diet results in a 10% LDL-C reduction and the other food components (plant sterols, viscous fiber, nuts and soy protein) contribute 5% each to LDL-C reduction, the combination diet could achieve a 30% LDL-C reduction. Results: In one month metabolic studies, approximately 30% reductions were seen in LDL-C comparable to 20mg of lovastatin with reduction also in CRP.
In long term ad libitum studies, at 3 years significant rises in HDL-C of 4-5% were seen with reductions in LDL-C of -7% (60 ITT subjects) and -17% (31 completers). Falls were seen in systolic and diastolic blood pressure. Removal of 2g plant sterols/day from the diet resulted in an approximately 10% rise in LDL-C. Addition of fruit (strawberries) to the diet improved palatability and reduced levels of circulating oxidized LDL. Conclusion: The combination or dietary portfolio approach is an effective strategy which can be developed further to minimize the reduction in LDL-C in the context of hyperlipidemia. Funding: The Almond Board of California, California Strawberry Commission, Loblaw Companies Limited, Canadian Research Chairs Program
7 PREVENTION IN LOWER RISK POPULATIONS S. Giampaoli. Istituto Superiore di Sanità, Rome, Italy High level of traditional risk factors for cardiovascular disease (CVD) – age, blood pressure (BP), total serum cholesterol (TC), diabetes, and smoking habit – explain most incident cardiovascular events. Persons with high levels of risk factors have high event rates whereas persons with favourable levels of risk factors rarely develop CVD. Favorable cardiovascular risk profile includes all these conditions: systolic/ diastolic BP<120/80mmHg, TC<200mg/dl, no smoking habit, no treatment for hypertension and dyslipidemia, no diabetes. Favorable risk profile group was studied and followed up by the ARIC, MRFIT, Chicago Gas Company studies and the Italian CUORE Project. Less than 10% of adult population fell in this group. Incidence of coronary and stroke events was rare, and age-adjusted death rate was lower when compared with unfavourable, high and very high risk profile. Similar results were published by studies focusing on health behaviours instead of risk factors, in particular the Nurses and Health Professionals studies and the EPIC-Norfolk Prospective population study.
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Funding: The studies presented are supported by grants from the Netherlands Heart Foundation and the Dutch Diabetes Research Foundation
4
3
Risk assessment for cardiovascular disease is primarily carried out as a guide to drug treatment. Because of the high cost of drugs, it has been necessary to do short-term (5-10 year) risk assessment to determine whether a particular drug treatment is cost-effective. This was particularly true of statins drugs which were patent-protected and quite expensive. More recently, since statins have gone off patent, there is a need for how do risk assessment as a guide to drug treatment. Generic statin therapy costs only about one-tenth the costs of patented-statin treatment. Further, aspirin therapy is inexpensive as well. Thus, the two major prevention drugs--statins and aspirin--are generic and cost-effectiveness is no longer an issue. The major issues then become safety and adherence. Selection of patients for drug therapy thus still is important, and identifying patients at lifetime risk for cardiovascular disease becomes more important. For this reason, it can be expected that much of the focus in risk assessment will shift from short-term risk to long-term risk. New modalities for lifetime risk assessment are needed.
A NEW TARGET FOR PREVENTION: INFLUENZA AS A TRIGGER OF ACUTE CORONARY SYNDROMES M. Madjid1,2, S.W. Casscells3. 1Texas Heart Institute Houston, TX, USA, 2 Baylor College of Medicine Houston, TX, USA, 3US Dept of Defense Washington, DC, USA Influenza in a preventable trigger of acute coronary syndromes. Influenza epidemics are almost always associated with sharp increases in cardiovascular events. Multiple studies have shown that influenza vaccination is associated with a remarkable reduction in risk of multiple cardiovascular endpoints including secondary MI, sudden cardiac arrest, stroke, composite interventional endpoints and hospitalization for cardiac causes. Influenza triggers acute coronary syndromes by destabilizing the already-present atherosclerotic vulnerable plaques. Influenza infection in apo E-deficient mice causes platelet aggregation, a marked increase in inflammatory cells in atherosclerotic plaques, and synergistic local and systemic inflammation. Influenza infection also increases the pro-thrombotic tendency. These data suggest an important role for influenza in development of acute cardiovascular events and a cardioprotective role for influenza vaccine. American Heart Association (AHA) and American College of Cardiology (ACC) have recently included influenza vaccination in their secondary prevention guidelines. However, the use of influenza vaccine in cardiac patients is still below the optimum level (about 50% in US). Influenza vaccination needs to be included in the cardiology prevention practice guidelines. Vaccination rate in patients with cardiovascular disease (CVD) needs to be improved. Clinical trials are needed to identify other high risk groups who may additionally benefit from influenza vaccination or use of antiviral agents for CVD prevention. Funding: US DoD T5 grant # W81XWH-04-20035
S2
WHAT IS CHANGING? SHORT-TERM VS. LONG-TERM RISK S. Grundy. University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA
Funding: none 5 HYPERTENSION AND STROKE G. Mancia. University of Milan-Bicocca, Milan, Italy This presentation will first summarize the epidemiological evidence that hypertension is a major risk factor for stroke, blood pressure values in excess of 115 mmHg systolic accounting for about two thirds of the stroke prevalence worldwide. It will then show that the hypertensionrelated risk of stroke is not irreversible because of the evidence obtained in randomized trials that when blood pressure is reduced by treatment the incidence of stroke can be markedly reduced. Few additional points will finally be presented. One, that in order to optimize protection against stroke in the hypertensive population at large BP should be reduced below 140/90 mmHg but that target
Journal of Clinical Lipidology, Vol 2, No 5S, October 2008
values 130/80 mmHg should be pursued in patients at high cardiovascular risk (diabetics and patients with a history of cardiovascular or renal disease) in whom treatment should be started already in the high normal BP range. Two, similar threshold and target BP values should be adopted for secondary prevention of stroke. Three, evidence that some antihypertensive drug classes possess blood pressure-independent specific cerebrovascular protective properties is at present not conclusive, the major protective role being apparently played by BP control which should be assessed also by out-of-office BP measurements. Four, the blood pressure-related protection can nevertheless be increased by complementary types of treatment such as those leading to lipid control, antiplatelet aggregation and prevention of atrial fibrillation. Finally, data will be presented that antihypertensive treatment can prevent stroke also in patients aged 80 years or more. Funding: none
6 THE USE OF A DIETARY PORTFOLIO APPROACH IN HYPERLIPIDIEMIA D.J.A. Jenkins, T.H. Nguyen, C.W.C. Kendall, J.M.W. Wong, A.R. Josse, N. Fozdar, A. Marchie, R.G. Josse, L.A. Leiter, W. Singer. St. Michael's Hospital and University of Toronto, Toronto, Canada Background: Major advances have been made in the pharmacological control of serum lipids and by comparison little use has been made of dietary components largely because individually the reductions in LDL-C are relatively small. ATP III recommended the use of viscous fiber and plant sterols to strengthen the diet effect and the FDA have added soy protein and nuts for which cholesterol lowering health claims can be made. Theoretically, if a low saturated fat, low cholesterol diet results in a 10% LDL-C reduction and the other food components (plant sterols, viscous fiber, nuts and soy protein) contribute 5% each to LDL-C reduction, the combination diet could achieve a 30% LDL-C reduction. Results: In one month metabolic studies, approximately 30% reductions were seen in LDL-C comparable to 20mg of lovastatin with reduction also in CRP.
In long term ad libitum studies, at 3 years significant rises in HDL-C of 4-5% were seen with reductions in LDL-C of -7% (60 ITT subjects) and -17% (31 completers). Falls were seen in systolic and diastolic blood pressure. Removal of 2g plant sterols/day from the diet resulted in an approximately 10% rise in LDL-C. Addition of fruit (strawberries) to the diet improved palatability and reduced levels of circulating oxidized LDL. Conclusion: The combination or dietary portfolio approach is an effective strategy which can be developed further to minimize the reduction in LDL-C in the context of hyperlipidemia. Funding: The Almond Board of California, California Strawberry Commission, Loblaw Companies Limited, Canadian Research Chairs Program
7 PREVENTION IN LOWER RISK POPULATIONS S. Giampaoli. Istituto Superiore di Sanità, Rome, Italy High level of traditional risk factors for cardiovascular disease (CVD) – age, blood pressure (BP), total serum cholesterol (TC), diabetes, and smoking habit – explain most incident cardiovascular events. Persons with high levels of risk factors have high event rates whereas persons with favourable levels of risk factors rarely develop CVD. Favorable cardiovascular risk profile includes all these conditions: systolic/ diastolic BP<120/80mmHg, TC<200mg/dl, no smoking habit, no treatment for hypertension and dyslipidemia, no diabetes. Favorable risk profile group was studied and followed up by the ARIC, MRFIT, Chicago Gas Company studies and the Italian CUORE Project. Less than 10% of adult population fell in this group. Incidence of coronary and stroke events was rare, and age-adjusted death rate was lower when compared with unfavourable, high and very high risk profile. Similar results were published by studies focusing on health behaviours instead of risk factors, in particular the Nurses and Health Professionals studies and the EPIC-Norfolk Prospective population study.
S3