- Email: [email protected]
Hypertension With Acute Coronary Syndrome and Heart Failure
THE EMCREG-INTERNATIONAL CONSENSUS PANEL RECOMMENDATIONS
Hypertension With Acute Coronary Syndrome and Heart Failure Deborah B. Diercks, MD E. Magnus Ohman, MD
From the Department of Emergency Medicine, University of California, Davis Medical Center, Sacramento, CA (Diercks); and Department of Medicine, Division of Cardiology, Duke University Medical Center, Duke Clinical Research Institute, Durham, NC (Ohman).
0196-0644/$-see front matter Copyright © 2008 by the American College of Emergency Physicians. doi:10.1016/j.annemergmed.2007.11.012
[Ann Emerg Med. 2008;51:S34-S36.]
ACUTE CORONARY SYNDROME Pathophysiology The heart bears the burden of target organ damage in patients with hypertension. Increased systolic blood pressure leads to myocardial hypertrophy, left ventricular hypertrophy, and impaired diastolic function. Diminished relaxation decreases coronary perfusion pressure and can lead to ischemia and myocardial infarction. Interestingly, nearly 50% of patients with acute heart failure syndromes present with increased blood pressure and maintenance of reasonable systolic function. A rapid increase in systolic blood pressure causes acute redistribution of fluid from the systemic to the pulmonary vasculature. It is postulated that acute heart failure syndromes from hypertension are due to congestion, rather than decreased cardiac output. In turn, the congestion increases left ventricular wall stress, decreases subendocardial perfusion, and may lead to myocardial apoptosis and necrosis.1 It has been well documented that hypertension is associated with increased risk of developing cardiovascular disease, as well as being associated with prognostic implications.2,3 The nature of this increased risk is multifactorial and involves narrowed coronary arteries, alterations in structural remodeling, and platelet activation.4,5 Hypertension results in cardiac hypertrophy without significant change in cardiac microcirculation, which may result in a heart that is less able to fulfill the output demands of normal circulation.5 This also may result in impaired coronary reserve, which in turn may increase the ischemic burden. In addition, chronic heart failure also results in structural changes within the arteries and arterioles. Hypertrophy may result in thickening of the media, which can decrease lumen area.4 Another mechanism that can further result in an acute coronary syndrome is the impact that hypertension has on coagulation and platelet activation.4 Changes to the coagulation and fibrinolytic pathway have been documented.4 In hypertensive patients, activity of plasminogen activator inhibitor has been shown to be high and impaired fibrinolysis has been shown to exist even after adjustment for other cardiac risk factors. The platelet activation in patients with hypertension is a S34 Annals of Emergency Medicine
result of increased shear force and endothelial activation and dysfunction. These factors lead to increased platelet aggregation that may lead to thrombus formation.6 Diagnostic Characteristics The objective in treatment of hypertension in patients with an acute coronary syndrome is reduction of ischemic symptoms.2 In patients with no history of increased blood pressure or mild hypertension, optimal blood pressure is therefore driven by characteristics based on the individual patient’s symptomatology. In patients who have a history of hypertension blood pressure or blood pressure greater than 160/ 100 mm Hg, reduction should be limited to 20% to 30% below the mean starting arterial blood pressure.2 This goal is similar to the guidelines for the management of hypertensive urgencies.7,8 Treatment The treatment of hypertension in the setting of an acute coronary syndrome often requires multiple agents. As shear forces, endothelial dysfunction, and platelet activation all play a role in the increased risk of morbidity associated with hypertension in the patient with acute coronary syndrome, treatment needs to address all of these areas. The guidelines for the American Heart Association/American College of Cardiology suggest the use of nitroglycerin and -blockers for the acute management of hypertension in the setting of acute coronary syndrome.2 Most antihypertensive agents have some antiplatelet function. This includes -blockers that have been shown to reduce plasminogen-activating inhibitor.5 The presence of severely increased blood pressure affects the treatment of patients with an acute coronary syndrome. In patients with an ST-segment-elevation myocardial infarction, the use of thrombolytics is contraindicated in patients with blood pressure greater than 185/100 mm Hg. In addition, in patients with severe hypertension and altered mental status, antithrombin agents should be used with caution until evaluation of the altered mental status is complete.
HEART FAILURE Pathophysiology The mechanisms for the development of heart failure are complex. Hypertension leads to the development of heart failure Volume , . : March
Diercks & Ohman through a complex process that results in remodeling of the myocardium.4 Chronic pressure overload, as in hypertension, results in persistent myocardial stress, which results in myocardial hypertrophy and an increase in myocardial thickness. Over time, this results in fiber hypertrophy, shortening, and impaired relaxation of the cardiac muscle.9 This mechanism is a result of changes at the cellular level. The remodeling of the myocardium is a result of cardiomyocyte size increase and changes in the interstitial and cardiovascular collagen matrix deposition.5,10 It has been suggested that although this is the mechanism attributed to the development of diastolic dysfunction, it may also occur to some extent in systolic dysfunction. These mechanisms relate the impact that hypertension has on the development of heart failure over time. However, there is limited understanding surrounding the pathophysiology of an increased blood pressure in the setting of acute heart failure symptoms. Management Consideration Patients with acute decompensated heart failure often present with increased blood pressure,11 which can occur in patients with systolic or diastolic dysfunction. In addition, the presence of increased blood pressure in the setting of acute symptoms may be an independent predictor of mortality. In an analysis from a large registry of heart failure patients, a third of the patients with systolic dysfunction presented with a systolic blood pressure greater than 140 mm Hg, whereas more than half of the patients with diastolic dysfunction had a blood pressure greater than 140 mm Hg. Further analysis from this data set showed that presenting systolic blood pressure was an independent predictor of inhospital and postdischarge mortality. The lowest rate of mortality was observed in patients presenting with a systolic blood pressure greater than 160 mm Hg, regardless of left ventricular function. This finding led the authors to suggest that systolic blood pressure at admission may have significant implications for the treatment of these patients.11 Treatment In patients with acute decompensated heart failure, symptoms may result from fluid shifts into the pulmonary vasculature. This occurs as a result of increased afterload and total body fluid overload. The association of blood pressure on prognosis has led to the suggestion that patients with acute symptoms should be stratified according to their initial blood pressure and treatment based on these stratifications.12 This approach addresses the “vasoactive” aspects of heart failure. Treatment for patients with blood pressure with increased systolic blood pressure (⬎140 mm Hg) has focused on the use of vasodilators. The first-line agent in this setting is nitroglycerin, which can be administered as bolus doses or a continuous infusion. The doses of nitroglycerin required to Volume , . : March
Hypertension With Acute Coronary Syndrome and Heart Failure produce a hemodynamic response are much higher than routinely used for an acute coronary syndrome. Doses may require rapid titration to greater than 120 g/min.13 Nitroprusside or intravenous angiotensin-converting enzyme inhibitors are also options for blood pressure reduction in this patient population. These agents are also acceptable treatments for the management of any patient with heart failure.14 Research is currently under way to define the role of agents such as vasopressin antagonist, adenosine antagonist, endothelin antagonists, and ularitide as potential treatment options for this group of patients.12 Although not an agent chosen specifically to lower blood pressure in congestive heart failure, nesiritide may decrease blood pressure in this setting. However, the US Food and Drug Administration notified physicians in July 2005 of an increase risk of renal failure and a trend toward an increase in 30-day mortality with the use of nesiritide in patients with decompensated heart failure.
SUMMARY RECOMMENDATIONS Acute Coronary Syndrome In patients with acute coronary syndrome, systolic blood pressure greater than 160 mm Hg and/or diastolic blood pressure greater than 100 mm Hg should be treated. The goal of treatment is to reduce the blood pressure by 20% to 30% from baseline value. Intravenous (or sublingual) nitroglycerin and intravenous -blockers are the preferred agents. Thrombolytics should be avoided in the presence of systolic blood pressure greater than 185 mm Hg and/or diastolic blood pressure greater than 110 mm Hg. Heart Failure and Pulmonary Edema Patients with acute heart failure and pulmonary edema should be stratified according to initial systolic blood pressure into 3 strata: greater than or equal to 140 mm Hg, 90 mm Hg to 139 mm Hg, or less than 90 mm Hg. Vasodilator treatment (in addition to diuretics) is recommended for patients with systolic blood pressure greater than or equal to 140 mm Hg or from 90 mm Hg to 139 mm Hg. Intravenous (or sublingual) nitroglycerin is the preferred agent. Intravenous angiotensin-converting enzyme inhibitors may be useful in this group of patients. Spontaneous reduction in blood pressure is common within the first 24 hours after acute heart failure and may require adjustment or termination of intravenous antihypertensive agents. Funding and support: By Annals policy, all authors are required to disclose any and all commercial, financial, and other relationships in any way related to the subject of this article, that might create any potential conflict of interest. See the Manuscript Submission Agreement in this issue for examples of specific conflicts covered by this statement. Dr. Diercks is part of the SCIOS speakers bureau. Annals of Emergency Medicine S35
Hypertension With Acute Coronary Syndrome and Heart Failure Address for correspondence: Deborah B. Diercks, MD, Department of Emergency Medicine, University of California, Davis Medical Center, 2315 Stockton Blvd., PSSB 2100, Sacramento, CA 95817; E-mail [email protected]. REFERENCES 1. Gheorghiade M, De Luca L, Fonarow GC, et al. Pathophysiologic targets in the early phase of acute heart failure syndromes. Am J Cardiol. 2005;96:11G-17G. 2. Braunwald E, Antman EM, Beasley JW, et al. ACC/AHA 2002 guideline update for the management of patients with unstable angina and non-ST-segment elevation myocardial infarction—summary article: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients With Unstable Angina). J Am Coll Cardiol. 2002;40:1366-1374. 3. Safar ME. Systolic blood pressure, pulse pressure and arterial stiffness as cardiovascular risk factors. Curr Opin Nephrol Hypertens. 2001;10:257-261. 4. Nadar SK, Tayebjee MH, Messerli F, et al. Target organ damage in hypertension: pathophysiology and implications for drug therapy. Curr Pharm Des. 2006;12:1581-1592. 5. Cohuet G, Struijker-Boudier H. Mechanisms of target organ damage caused by hypertension: therapeutic potential. Pharmacol Ther. 2006;111:81-98.
S36 Annals of Emergency Medicine
Diercks & Ohman 6. Skyschally A, Erbel R, Heusch G. Coronary microembolization. Circ J. 2003;67:279-286. 7. Elliot WJ. Clinical features and management of selected hypertensive emergencies. J Clin Hypertens (Greenwich). 2004;6: 587-592. 8. Heusch G, Schulz R, Haude M, et al. Coronary microembolization. J Mol Cell Cardiol. 2004;37:23-31. 9. Sasayama S, Franklin D, Ross J Jr. Hyperfunction with normal inotropic state of the hypertrophied left ventricle. Am J Physiol. 1977;232:H418-425. 10. Manabe I, Shindo T, Nagai R. Gene expression in fibroblasts and fibrosis: involvement in cardiac hypertrophy. Circ Res. 2002;91: 1103-1113. 11. Gheorghiade M, Abraham WT, Albert NM, et al. Systolic blood pressure at admission, clinical characteristics, and outcomes in patients hospitalized with acute heart failure. JAMA. 2006;296: 2217-2226. 12. Shin D, Brandimarte F, De Luca L, et al. Review of current and investigational pharmacologic agents for acute heart failure syndromes. Am J Cardiol. 2007;99:4A-23A. 13. Elkayam U, Akhter MW, Kan S. Intravenous nitroglycerin in the treatment of decompensated heart failure: potential benefits and limitations. J Cardiovasc Pharmacol Ther. 2004;9:227-241. 14. Heart Failure Society of America. HFSA 2006 comprehensive heart failure practice guideline. J Card Fail. 2006;12:e1-2.
Volume , . : March
Hypertension With Acute Coronary Syndrome and Heart Failure Deborah B. Diercks, MD E. Magnus Ohman, MD
From the Department of Emergency Medicine, University of California, Davis Medical Center, Sacramento, CA (Diercks); and Department of Medicine, Division of Cardiology, Duke University Medical Center, Duke Clinical Research Institute, Durham, NC (Ohman).
0196-0644/$-see front matter Copyright © 2008 by the American College of Emergency Physicians. doi:10.1016/j.annemergmed.2007.11.012
[Ann Emerg Med. 2008;51:S34-S36.]
ACUTE CORONARY SYNDROME Pathophysiology The heart bears the burden of target organ damage in patients with hypertension. Increased systolic blood pressure leads to myocardial hypertrophy, left ventricular hypertrophy, and impaired diastolic function. Diminished relaxation decreases coronary perfusion pressure and can lead to ischemia and myocardial infarction. Interestingly, nearly 50% of patients with acute heart failure syndromes present with increased blood pressure and maintenance of reasonable systolic function. A rapid increase in systolic blood pressure causes acute redistribution of fluid from the systemic to the pulmonary vasculature. It is postulated that acute heart failure syndromes from hypertension are due to congestion, rather than decreased cardiac output. In turn, the congestion increases left ventricular wall stress, decreases subendocardial perfusion, and may lead to myocardial apoptosis and necrosis.1 It has been well documented that hypertension is associated with increased risk of developing cardiovascular disease, as well as being associated with prognostic implications.2,3 The nature of this increased risk is multifactorial and involves narrowed coronary arteries, alterations in structural remodeling, and platelet activation.4,5 Hypertension results in cardiac hypertrophy without significant change in cardiac microcirculation, which may result in a heart that is less able to fulfill the output demands of normal circulation.5 This also may result in impaired coronary reserve, which in turn may increase the ischemic burden. In addition, chronic heart failure also results in structural changes within the arteries and arterioles. Hypertrophy may result in thickening of the media, which can decrease lumen area.4 Another mechanism that can further result in an acute coronary syndrome is the impact that hypertension has on coagulation and platelet activation.4 Changes to the coagulation and fibrinolytic pathway have been documented.4 In hypertensive patients, activity of plasminogen activator inhibitor has been shown to be high and impaired fibrinolysis has been shown to exist even after adjustment for other cardiac risk factors. The platelet activation in patients with hypertension is a S34 Annals of Emergency Medicine
result of increased shear force and endothelial activation and dysfunction. These factors lead to increased platelet aggregation that may lead to thrombus formation.6 Diagnostic Characteristics The objective in treatment of hypertension in patients with an acute coronary syndrome is reduction of ischemic symptoms.2 In patients with no history of increased blood pressure or mild hypertension, optimal blood pressure is therefore driven by characteristics based on the individual patient’s symptomatology. In patients who have a history of hypertension blood pressure or blood pressure greater than 160/ 100 mm Hg, reduction should be limited to 20% to 30% below the mean starting arterial blood pressure.2 This goal is similar to the guidelines for the management of hypertensive urgencies.7,8 Treatment The treatment of hypertension in the setting of an acute coronary syndrome often requires multiple agents. As shear forces, endothelial dysfunction, and platelet activation all play a role in the increased risk of morbidity associated with hypertension in the patient with acute coronary syndrome, treatment needs to address all of these areas. The guidelines for the American Heart Association/American College of Cardiology suggest the use of nitroglycerin and -blockers for the acute management of hypertension in the setting of acute coronary syndrome.2 Most antihypertensive agents have some antiplatelet function. This includes -blockers that have been shown to reduce plasminogen-activating inhibitor.5 The presence of severely increased blood pressure affects the treatment of patients with an acute coronary syndrome. In patients with an ST-segment-elevation myocardial infarction, the use of thrombolytics is contraindicated in patients with blood pressure greater than 185/100 mm Hg. In addition, in patients with severe hypertension and altered mental status, antithrombin agents should be used with caution until evaluation of the altered mental status is complete.
HEART FAILURE Pathophysiology The mechanisms for the development of heart failure are complex. Hypertension leads to the development of heart failure Volume , . : March
Diercks & Ohman through a complex process that results in remodeling of the myocardium.4 Chronic pressure overload, as in hypertension, results in persistent myocardial stress, which results in myocardial hypertrophy and an increase in myocardial thickness. Over time, this results in fiber hypertrophy, shortening, and impaired relaxation of the cardiac muscle.9 This mechanism is a result of changes at the cellular level. The remodeling of the myocardium is a result of cardiomyocyte size increase and changes in the interstitial and cardiovascular collagen matrix deposition.5,10 It has been suggested that although this is the mechanism attributed to the development of diastolic dysfunction, it may also occur to some extent in systolic dysfunction. These mechanisms relate the impact that hypertension has on the development of heart failure over time. However, there is limited understanding surrounding the pathophysiology of an increased blood pressure in the setting of acute heart failure symptoms. Management Consideration Patients with acute decompensated heart failure often present with increased blood pressure,11 which can occur in patients with systolic or diastolic dysfunction. In addition, the presence of increased blood pressure in the setting of acute symptoms may be an independent predictor of mortality. In an analysis from a large registry of heart failure patients, a third of the patients with systolic dysfunction presented with a systolic blood pressure greater than 140 mm Hg, whereas more than half of the patients with diastolic dysfunction had a blood pressure greater than 140 mm Hg. Further analysis from this data set showed that presenting systolic blood pressure was an independent predictor of inhospital and postdischarge mortality. The lowest rate of mortality was observed in patients presenting with a systolic blood pressure greater than 160 mm Hg, regardless of left ventricular function. This finding led the authors to suggest that systolic blood pressure at admission may have significant implications for the treatment of these patients.11 Treatment In patients with acute decompensated heart failure, symptoms may result from fluid shifts into the pulmonary vasculature. This occurs as a result of increased afterload and total body fluid overload. The association of blood pressure on prognosis has led to the suggestion that patients with acute symptoms should be stratified according to their initial blood pressure and treatment based on these stratifications.12 This approach addresses the “vasoactive” aspects of heart failure. Treatment for patients with blood pressure with increased systolic blood pressure (⬎140 mm Hg) has focused on the use of vasodilators. The first-line agent in this setting is nitroglycerin, which can be administered as bolus doses or a continuous infusion. The doses of nitroglycerin required to Volume , . : March
Hypertension With Acute Coronary Syndrome and Heart Failure produce a hemodynamic response are much higher than routinely used for an acute coronary syndrome. Doses may require rapid titration to greater than 120 g/min.13 Nitroprusside or intravenous angiotensin-converting enzyme inhibitors are also options for blood pressure reduction in this patient population. These agents are also acceptable treatments for the management of any patient with heart failure.14 Research is currently under way to define the role of agents such as vasopressin antagonist, adenosine antagonist, endothelin antagonists, and ularitide as potential treatment options for this group of patients.12 Although not an agent chosen specifically to lower blood pressure in congestive heart failure, nesiritide may decrease blood pressure in this setting. However, the US Food and Drug Administration notified physicians in July 2005 of an increase risk of renal failure and a trend toward an increase in 30-day mortality with the use of nesiritide in patients with decompensated heart failure.
SUMMARY RECOMMENDATIONS Acute Coronary Syndrome In patients with acute coronary syndrome, systolic blood pressure greater than 160 mm Hg and/or diastolic blood pressure greater than 100 mm Hg should be treated. The goal of treatment is to reduce the blood pressure by 20% to 30% from baseline value. Intravenous (or sublingual) nitroglycerin and intravenous -blockers are the preferred agents. Thrombolytics should be avoided in the presence of systolic blood pressure greater than 185 mm Hg and/or diastolic blood pressure greater than 110 mm Hg. Heart Failure and Pulmonary Edema Patients with acute heart failure and pulmonary edema should be stratified according to initial systolic blood pressure into 3 strata: greater than or equal to 140 mm Hg, 90 mm Hg to 139 mm Hg, or less than 90 mm Hg. Vasodilator treatment (in addition to diuretics) is recommended for patients with systolic blood pressure greater than or equal to 140 mm Hg or from 90 mm Hg to 139 mm Hg. Intravenous (or sublingual) nitroglycerin is the preferred agent. Intravenous angiotensin-converting enzyme inhibitors may be useful in this group of patients. Spontaneous reduction in blood pressure is common within the first 24 hours after acute heart failure and may require adjustment or termination of intravenous antihypertensive agents. Funding and support: By Annals policy, all authors are required to disclose any and all commercial, financial, and other relationships in any way related to the subject of this article, that might create any potential conflict of interest. See the Manuscript Submission Agreement in this issue for examples of specific conflicts covered by this statement. Dr. Diercks is part of the SCIOS speakers bureau. Annals of Emergency Medicine S35
Hypertension With Acute Coronary Syndrome and Heart Failure Address for correspondence: Deborah B. Diercks, MD, Department of Emergency Medicine, University of California, Davis Medical Center, 2315 Stockton Blvd., PSSB 2100, Sacramento, CA 95817; E-mail [email protected]. REFERENCES 1. Gheorghiade M, De Luca L, Fonarow GC, et al. Pathophysiologic targets in the early phase of acute heart failure syndromes. Am J Cardiol. 2005;96:11G-17G. 2. Braunwald E, Antman EM, Beasley JW, et al. ACC/AHA 2002 guideline update for the management of patients with unstable angina and non-ST-segment elevation myocardial infarction—summary article: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients With Unstable Angina). J Am Coll Cardiol. 2002;40:1366-1374. 3. Safar ME. Systolic blood pressure, pulse pressure and arterial stiffness as cardiovascular risk factors. Curr Opin Nephrol Hypertens. 2001;10:257-261. 4. Nadar SK, Tayebjee MH, Messerli F, et al. Target organ damage in hypertension: pathophysiology and implications for drug therapy. Curr Pharm Des. 2006;12:1581-1592. 5. Cohuet G, Struijker-Boudier H. Mechanisms of target organ damage caused by hypertension: therapeutic potential. Pharmacol Ther. 2006;111:81-98.
S36 Annals of Emergency Medicine
Diercks & Ohman 6. Skyschally A, Erbel R, Heusch G. Coronary microembolization. Circ J. 2003;67:279-286. 7. Elliot WJ. Clinical features and management of selected hypertensive emergencies. J Clin Hypertens (Greenwich). 2004;6: 587-592. 8. Heusch G, Schulz R, Haude M, et al. Coronary microembolization. J Mol Cell Cardiol. 2004;37:23-31. 9. Sasayama S, Franklin D, Ross J Jr. Hyperfunction with normal inotropic state of the hypertrophied left ventricle. Am J Physiol. 1977;232:H418-425. 10. Manabe I, Shindo T, Nagai R. Gene expression in fibroblasts and fibrosis: involvement in cardiac hypertrophy. Circ Res. 2002;91: 1103-1113. 11. Gheorghiade M, Abraham WT, Albert NM, et al. Systolic blood pressure at admission, clinical characteristics, and outcomes in patients hospitalized with acute heart failure. JAMA. 2006;296: 2217-2226. 12. Shin D, Brandimarte F, De Luca L, et al. Review of current and investigational pharmacologic agents for acute heart failure syndromes. Am J Cardiol. 2007;99:4A-23A. 13. Elkayam U, Akhter MW, Kan S. Intravenous nitroglycerin in the treatment of decompensated heart failure: potential benefits and limitations. J Cardiovasc Pharmacol Ther. 2004;9:227-241. 14. Heart Failure Society of America. HFSA 2006 comprehensive heart failure practice guideline. J Card Fail. 2006;12:e1-2.
Volume , . : March