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ischemic heart disease
AJH
1999;12:33S–34S
A Chronotherapeutic Approach to the Management of High-Risk Patients With Hypertension/Ischemic Heart Disease Introduction Henry R. Black, Chairman
H
eart disease is the most common cause of death in the United States. As all of us are aware, hypertension remains a major risk factor for cardiovascular disease and mortality. We who are responsible for treating diseases of the heart and blood vessels must achieve better control of hypertension if we hope to reduce, in any meaningful way, the unacceptable toll taken by cardiovascular diseases. According to NHANES III phase 2 (1991–1994),1 the rates of awareness, treatment, and control of hypertension have fallen since NHANES III phase 1 (1988 –1991). As clinicians, we need to recognize and deal with this problem, using all the techniques at our disposal, and to begin to include options that may differ from the routines we are used to. One of the newer management approaches is the application of the study of naturally occurring bodily rhythms (chronobiology) to patient management, hence chronotherapy. This supplement, based on the symposium entitled “A Chronotherapeutic Approach to the Management of High Risk Patients With Hypertension and Ischemic Heart Disease,” addresses these issues and presents the benefits of a chronotherapeutic approach in controlling hypertension and perhaps reducing the incidence of cardiovascular disease.
From the Department of Preventive Medicine, Rush-PresbyterianSt. Luke’s Medical Center, Chicago, Illinois. Address correspondence and reprint requests to Henry R. Black, MD, Rush-Presbyterian-St. Luke’s Medical Center, Suite 117, 1725 W. Harrison Street, Chicago, IL 60612.
© 1999 by the American Journal of Hypertension, Ltd. Published by Elsevier Science, Inc.
OVERVIEW OF PROGRAM From James Muller’s article we learn about the circadian variation of many cardiovascular events, including myocardial infarction (MI), sudden coronary death, ischemic stroke, unstable angina, and non–Qwave acute MI. All of these demonstrate a peak incidence in the morning hours.2 Muller goes on to discuss the triggers of such events, such as the morning rise in cortisol and catecholamines, which can promote increased vascular tone, cardiac contractility, and heart rate. He suggests that blunting these morning surges might have a beneficial effect.3 In his article, Dr. William White talks about the relevance of myocardial oxygen demand, a key indicator of the workload on the heart. Because it is difficult to measure this parameter directly, a surrogate marker—rate-pressure product (heart rate multiplied by systolic BP)—is used. Dr. White goes on to describe the results of a recently published clinical trial in which the use of the chronotherapeutic agent COERverapamil, was shown to decrease the rate-pressure product significantly more than the extended- release preparation of nifedipine GITS.4 In his article, Dr. William Elliott describes the circadian variation of various events and discusses the particular risks of nocturnal hypotension in the elderly. Among these are the risk of increased cerebral ischemia and a danger of other ischemic phenomena, such as anterior ischemic optic neuropathy.5 Finally, Dr. Suzanne Oparil addresses the particular challenge of treating the hypertensive patient who already has coronary artery disease. Dr. Oparil discusses the importance of cardiovascular triggers in this higher-risk group and makes the point that the management of hypertensive patients with coronary 0895-7061/99/$20.00 PII S0895-7061(98)00277-5
34S
AJH–FEBRUARY 1999 –VOL. 12, NO. 2, PART 2
BLACK
heart disease would be helped by using an agent that lowers blood pressure effectively and decreases the parameters that tend to make angina worse, such as heart rate.6 THE CONVINCE TRIAL To confirm the benefits of chronotherapy in managing patients with hypertension, a major multinational clinical trial has been undertaken by Searle (Skokie, IL). The Controlled Onset Verapamil Investigation of Cardiovascular Endpoints (CONVINCE) trial will involve more than 15,000 patients enrolled in 14 countries in North America and Europe.2 CONVINCE compares two treatment regimens. One treatment cohort will receive COER-verapamil as the initial treatment while the other will receive either a b-blocker (atenolol) or diuretic (hydrochlorothiazide) as initial treatment, as chosen for them by their study physician. Study participants will be followed for an average of 5 years to determine which of the two regimens better reduces heart attack, stroke, and cardiovascular death. The trial is designed to determine if nondihydropyridine calcium antagonists are at least equivalent to standard-of-care therapy in protecting against cardiovascular events. An important secondary endpoint is to ascertain just when these events occur, which will
validate the rationale of using a chronotherapeutic approach to treatment. The articles in this supplement provide an overview of the issue of chronobiology and chronotherapeutics. It will be important to know whether the results of CONVINCE and ongoing trials affect our management of patients with hypertension. REFERENCES 1.
National Center for Health Statistics: Health, United States, 1996. Hyattsville, MD, US Public Health Service, 1997.
2.
Black HR, Elliott WJ, Neaton JD, et al: Rationale and design for the Controlled ONset Verapamil INvestigation of Cardiovascular Endpoints (CONVINCE) trial. Controlled Clin Trials 1998;19:370 –390.
3.
Muller JE: Circadian variation in cardiovascular events. Am J Hypertens 1999;12:35S– 42S.
4.
White WB: Heart rate and the rate-pressure product as determinants of cardiovascular risk in patients with hypertension. Am J Hypertens 1999;12:50S–55S.
5.
Elliott WJ: Circadian variation in blood pressure: implications for the elderly patient. Am J Hypertens 1999;12: 43S– 49S.
6.
Oparil S: Management of the hypertensive patient with coronary artery disease. Am J Hypertens 1999;12:56S– 62S.
1999;12:33S–34S
A Chronotherapeutic Approach to the Management of High-Risk Patients With Hypertension/Ischemic Heart Disease Introduction Henry R. Black, Chairman
H
eart disease is the most common cause of death in the United States. As all of us are aware, hypertension remains a major risk factor for cardiovascular disease and mortality. We who are responsible for treating diseases of the heart and blood vessels must achieve better control of hypertension if we hope to reduce, in any meaningful way, the unacceptable toll taken by cardiovascular diseases. According to NHANES III phase 2 (1991–1994),1 the rates of awareness, treatment, and control of hypertension have fallen since NHANES III phase 1 (1988 –1991). As clinicians, we need to recognize and deal with this problem, using all the techniques at our disposal, and to begin to include options that may differ from the routines we are used to. One of the newer management approaches is the application of the study of naturally occurring bodily rhythms (chronobiology) to patient management, hence chronotherapy. This supplement, based on the symposium entitled “A Chronotherapeutic Approach to the Management of High Risk Patients With Hypertension and Ischemic Heart Disease,” addresses these issues and presents the benefits of a chronotherapeutic approach in controlling hypertension and perhaps reducing the incidence of cardiovascular disease.
From the Department of Preventive Medicine, Rush-PresbyterianSt. Luke’s Medical Center, Chicago, Illinois. Address correspondence and reprint requests to Henry R. Black, MD, Rush-Presbyterian-St. Luke’s Medical Center, Suite 117, 1725 W. Harrison Street, Chicago, IL 60612.
© 1999 by the American Journal of Hypertension, Ltd. Published by Elsevier Science, Inc.
OVERVIEW OF PROGRAM From James Muller’s article we learn about the circadian variation of many cardiovascular events, including myocardial infarction (MI), sudden coronary death, ischemic stroke, unstable angina, and non–Qwave acute MI. All of these demonstrate a peak incidence in the morning hours.2 Muller goes on to discuss the triggers of such events, such as the morning rise in cortisol and catecholamines, which can promote increased vascular tone, cardiac contractility, and heart rate. He suggests that blunting these morning surges might have a beneficial effect.3 In his article, Dr. William White talks about the relevance of myocardial oxygen demand, a key indicator of the workload on the heart. Because it is difficult to measure this parameter directly, a surrogate marker—rate-pressure product (heart rate multiplied by systolic BP)—is used. Dr. White goes on to describe the results of a recently published clinical trial in which the use of the chronotherapeutic agent COERverapamil, was shown to decrease the rate-pressure product significantly more than the extended- release preparation of nifedipine GITS.4 In his article, Dr. William Elliott describes the circadian variation of various events and discusses the particular risks of nocturnal hypotension in the elderly. Among these are the risk of increased cerebral ischemia and a danger of other ischemic phenomena, such as anterior ischemic optic neuropathy.5 Finally, Dr. Suzanne Oparil addresses the particular challenge of treating the hypertensive patient who already has coronary artery disease. Dr. Oparil discusses the importance of cardiovascular triggers in this higher-risk group and makes the point that the management of hypertensive patients with coronary 0895-7061/99/$20.00 PII S0895-7061(98)00277-5
34S
AJH–FEBRUARY 1999 –VOL. 12, NO. 2, PART 2
BLACK
heart disease would be helped by using an agent that lowers blood pressure effectively and decreases the parameters that tend to make angina worse, such as heart rate.6 THE CONVINCE TRIAL To confirm the benefits of chronotherapy in managing patients with hypertension, a major multinational clinical trial has been undertaken by Searle (Skokie, IL). The Controlled Onset Verapamil Investigation of Cardiovascular Endpoints (CONVINCE) trial will involve more than 15,000 patients enrolled in 14 countries in North America and Europe.2 CONVINCE compares two treatment regimens. One treatment cohort will receive COER-verapamil as the initial treatment while the other will receive either a b-blocker (atenolol) or diuretic (hydrochlorothiazide) as initial treatment, as chosen for them by their study physician. Study participants will be followed for an average of 5 years to determine which of the two regimens better reduces heart attack, stroke, and cardiovascular death. The trial is designed to determine if nondihydropyridine calcium antagonists are at least equivalent to standard-of-care therapy in protecting against cardiovascular events. An important secondary endpoint is to ascertain just when these events occur, which will
validate the rationale of using a chronotherapeutic approach to treatment. The articles in this supplement provide an overview of the issue of chronobiology and chronotherapeutics. It will be important to know whether the results of CONVINCE and ongoing trials affect our management of patients with hypertension. REFERENCES 1.
National Center for Health Statistics: Health, United States, 1996. Hyattsville, MD, US Public Health Service, 1997.
2.
Black HR, Elliott WJ, Neaton JD, et al: Rationale and design for the Controlled ONset Verapamil INvestigation of Cardiovascular Endpoints (CONVINCE) trial. Controlled Clin Trials 1998;19:370 –390.
3.
Muller JE: Circadian variation in cardiovascular events. Am J Hypertens 1999;12:35S– 42S.
4.
White WB: Heart rate and the rate-pressure product as determinants of cardiovascular risk in patients with hypertension. Am J Hypertens 1999;12:50S–55S.
5.
Elliott WJ: Circadian variation in blood pressure: implications for the elderly patient. Am J Hypertens 1999;12: 43S– 49S.
6.
Oparil S: Management of the hypertensive patient with coronary artery disease. Am J Hypertens 1999;12:56S– 62S.