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  • 2 nd most common reason for visit All family physicians should be experts at HTN.
  • Hypertension is an important contributing risk factor for morbidity and mortality from both cardiovascular (CV) and renal disease. Hypertension is one of the most significant contributing factors to the development of CV and renal disease. Complications of hypertension include coronary artery disease, congestive heart failure, stroke, renal disease (including end-stage renal disease), and peripheral vascular disease. These diseases account for significant disability, loss of productivity, and decreased quality of life for many Americans. National High Blood Pressure Education Program Working Group. National High Blood Pressure Education Program Working Group report on primary prevention of hypertension. Arch Intern Med. 1993;153:186-208.
  • Hypertension

    1. 1. Hypertension in Diabetes Mellitus
    2. 2. Hypertension: The Silent Killer Facts & Figures <ul><li>50 million Americans & 1 billion worldwide affected </li></ul><ul><li>Most common primary care diagnosis (35 million visits annually) </li></ul><ul><li>Normotensive at age 55 have 90% lifetime risk of Hypertension </li></ul><ul><li>Continuous & consistent relationship with CVD </li></ul><ul><ul><li>Between ages 40-70, starting from 115/75 </li></ul></ul><ul><ul><li>CVD risk doubles with each increment of 20/10 </li></ul></ul>
    3. 3. Top Three Countries for Diabetes Data from King H et al. Diabetes Care . 1998;21:1414-1431.
    4. 4. What is Hypertension? JNC 7 Definition Hypertension 2003;42:1206-52 Blood Pressure (mm Hg) Category Systolic Diastolic <120 and <80 Normal 120-139 or 80-89 Prehypertension 140-159 or 90-99 Stage 1 hypertension ≥ 160 or ≥100 Stage 2 hypertension
    5. 5. Types of Hypertension <ul><li>Essential hypertension </li></ul><ul><ul><li>90% </li></ul></ul><ul><ul><li>No underlying cause </li></ul></ul><ul><li>Secondary hypertension </li></ul><ul><ul><li>Underlying cause </li></ul></ul>
    6. 6. Causes of Secondary Hypertension <ul><li>Renal </li></ul><ul><ul><li>Parenchymal </li></ul></ul><ul><ul><li>Vascular </li></ul></ul><ul><ul><li>Others </li></ul></ul><ul><li>Endocrine </li></ul><ul><li>Neurogenic </li></ul><ul><li>Miscellaneous </li></ul><ul><li>Unknown </li></ul>
    7. 7. Hypertension: Predisposing factors <ul><li>Age > 60 years </li></ul><ul><li>Sex (men and postmenopausal women) </li></ul><ul><li>Family history of cardiovascular disease </li></ul><ul><li>Smoking </li></ul><ul><li>High cholesterol diet </li></ul><ul><li>Co-existing disorders such as diabetes, obesity and hyperlipidaemia </li></ul><ul><li>High intake of alcohol </li></ul><ul><li>Sedentary life style </li></ul>
    8. 8. Hypertension: A Significant CV and Renal Disease Risk Factor National High Blood Pressure Education Program Working Group. Arch Intern Med. 1993;153:186-208.
    9. 9. CV Mortality Risk Doubles with Each 20/10 mm Hg BP Increment* *Individuals aged 40-69 years, starting at BP 115/75 mm Hg. CV, cardiovascular; SBP, systolic blood pressure; DBP, diastolic blood pressure Lewington S, et al. Lancet . 2002; 60:1903-1913. JNC VII. JAMA. 2003. CV mortality risk SBP/DBP (mm Hg) 0 1 2 3 4 5 6 7 8 115/75 135/85 155/95 175/105
    10. 10. Pathophysiology of hypertension in DM <ul><li>The derangements in glucose, lipid, and protein metabolism lead to </li></ul><ul><li>functional abnormalities in autonomic nerves </li></ul><ul><li>overproduction of vasoconstrictor factors that increase vascular tone </li></ul><ul><li>concomitant reductions in the biologic actions of vasodilators </li></ul><ul><li> resulting in an increase in BP </li></ul>
    11. 11. Vasoactive substances <ul><li>Cause structural changes in the CV system and in the kidney through effects on: </li></ul><ul><li>Vascular smooth muscle cell hypertrophy </li></ul><ul><li>Hyperplasia, angiogenesis, cellular apoptosis, macrophage/fibroblast activation with augmented formation of extracellular matrix </li></ul><ul><li>Adhesive interactions of circulating leukocytes and platelets with the vessel wall </li></ul>
    12. 12. Processes important in the development or perpetuation of hypertension in diabetics <ul><li>Alterations in the balanced production of vasodilator & vasoconstrictor substances from the endothelium </li></ul><ul><li>Altered vascular smooth muscle responses to these substances </li></ul><ul><li>Resistance of peripheral tissues & selected lipid metabolic processes to the actions of insulin </li></ul><ul><li>Alterations in the cellular & extracellular elements that comprise the vessel wall </li></ul>
    13. 13. Reactive oxygen species (ROS) <ul><li>Diabetics—increased metabolic processes that produce reactive oxygen species (ROS) </li></ul><ul><li>ROS serve as signaling mechanisms mediate many of the functional & structural vascular abnormalities observed in diabetics </li></ul><ul><li>Thus, hypertension in diabetics probably results from a series of interrelated, complex functional and structural abnormalities </li></ul>
    14. 14. Management: JNC 7 GUIDELINES
    15. 15. What are the goals of therapy? <ul><li><140/90 for patients without diabetes or renal disease </li></ul><ul><ul><li>Most patients who achieve their systolic goal will also achieve their diastolic goal </li></ul></ul><ul><li><130/80 for patients with diabetes or renal disease </li></ul><ul><ul><ul><li>JNC VII Guidelines </li></ul></ul></ul>
    16. 16. But… There are Reasons for Inadequate BP Control <ul><li>Poor compliance to lifestyle modifications </li></ul><ul><li>Acceptance of inadequate control by physician </li></ul><ul><li>Difficulty achieving BP control with one agent/suboptimal regimens </li></ul><ul><li>BP goals are more aggressive than in previous years </li></ul><ul><li>Lack of compliance due to: </li></ul><ul><ul><li>Perceived side effects of antihypertensive medication(s) </li></ul></ul><ul><ul><li>Frequency of dosing/multiple agents to attain control </li></ul></ul>JNC VI. Arch Intern Med. 1997
    17. 17. And that leads to… <ul><li>Refractory hypertension – </li></ul><ul><li>Defined by a blood pressure of at least 140/90 or at least 130/80 in patients with diabetes or renal disease despite adherence to treatment with full doses of at least three antihypertensive medications, including a diuretic. </li></ul><ul><li> </li></ul><ul><li>JNC VII Guidelines </li></ul>
    18. 18. <ul><li>Refractory hypertension is primarily a systolic and age related problem </li></ul><ul><li>It affects 5-30% of the general population with hypertension </li></ul><ul><li>Patients with refractory hypertension have an increased risk of </li></ul><ul><ul><li>Stroke, </li></ul></ul><ul><ul><li>Aortic Dissecting Aneurysm, </li></ul></ul><ul><ul><li>Myocardial Infarction, </li></ul></ul><ul><ul><li>Congestive Heart Failure and </li></ul></ul><ul><ul><li>Renal failure compared to other hypertensive patients </li></ul></ul><ul><ul><li>J Hypertens. 2005;23(8):1441-4, Hypertension. 1988;11(3 Pt 2):II71-5, Minerva Med. 2003;94(4):201-14. </li></ul></ul>Refractory Hypertension leads to
    19. 19. Causes of Refractory Hypertension <ul><li>The main reasons why hypertension may be unresponsive to a standard antihypertensive treatment include: </li></ul><ul><ul><li>Incorrect diagnosis, </li></ul></ul><ul><ul><li>Secondary forms of hypertension, </li></ul></ul><ul><ul><li>Inadequate antihypertensive drug regimen, </li></ul></ul><ul><ul><li>Associated factors or diseases, </li></ul></ul><ul><ul><li>Use of non-steroidal anti-inflammatory drugs, </li></ul></ul><ul><ul><li>Non-compliance with antihypertensive treatment. </li></ul></ul><ul><li>Although non-compliance may also be common in patients with well-controlled blood pressure, poor compliance with drug treatment is generally recognized as a major cause of unsatisfactory blood pressure control. </li></ul>
    20. 20. Approach to Resistant Hypertension <ul><li>Establish “true resistance” </li></ul><ul><ul><li>Measure BP accurately </li></ul></ul><ul><ul><li>Consider “White Coat Hypertension” </li></ul></ul><ul><ul><li>Consider “Pseudoresistance” </li></ul></ul><ul><ul><li>Medication Adherence </li></ul></ul><ul><ul><li>Consider secondary causes </li></ul></ul>
    21. 21. Accurate BP Measurement <ul><li>“ Persons should be seated quietly for 5 minutes with feet on the floor and the arm supported at heart level” </li></ul><ul><li>Cuff must be appropriately sized (cuff bladder must encircle 80% of the arm) </li></ul><ul><li>Check both arms and a leg (or palpate pulses carefully) </li></ul><ul><li>Caffeine and Tobacco can transiently raise BP substantially </li></ul>
    22. 22. Approach to Resistant Hypertension <ul><li>Establish “true resistance” </li></ul><ul><ul><li>Measure BP accurately </li></ul></ul><ul><ul><li>Consider “White Coat Hypertension” </li></ul></ul><ul><ul><li>Consider “Pseudoresistance” </li></ul></ul><ul><ul><li>Medication Adherence </li></ul></ul><ul><ul><li>Consider secondary causes </li></ul></ul>
    23. 23. White Coat Hypertension <ul><li>20-30% of Apparently Resistant Hypertension May be due to “White-Coat Hypertension” </li></ul><ul><li>Patients with WCH have an increased risk of CV events and often have some degree of end organ damage </li></ul><ul><li>Use home or ambulatory monitoring to sort out </li></ul>
    24. 24. Approach to Resistant Hypertension <ul><li>Establish “true resistance” </li></ul><ul><ul><li>Measure BP accurately </li></ul></ul><ul><ul><li>Consider “White Coat Hypertension” </li></ul></ul><ul><ul><li>Consider “Pseudoresistance” </li></ul></ul><ul><ul><li>Medication Adherence </li></ul></ul><ul><ul><li>Consider secondary causes </li></ul></ul>
    25. 25. Pseudoresistance <ul><li>Pseudohypertension </li></ul><ul><li>Non-adherence may account for up to 50% of resistant cases </li></ul><ul><li>Inadequate Regimen </li></ul><ul><ul><li>Especially inadequate diuretic component </li></ul></ul><ul><li>Interfering medicines and substances also need to be considered </li></ul><ul><ul><li>NSAIDs </li></ul></ul><ul><ul><li>Excessive Alcohol, Caffeine, or Tobacco </li></ul></ul><ul><ul><li>Excessive Salt Intake </li></ul></ul><ul><ul><li>Drugs of Abuse </li></ul></ul><ul><ul><li>Oral contraceptives </li></ul></ul>
    26. 26. Approach to Resistant Hypertension <ul><li>Establish “true resistance” </li></ul><ul><ul><li>Measure BP accurately </li></ul></ul><ul><ul><li>Consider “White Coat Hypertension” </li></ul></ul><ul><ul><li>Consider “Pseudoresistance” </li></ul></ul><ul><ul><li>Medication Adherence </li></ul></ul><ul><ul><li>Consider secondary causes </li></ul></ul>
    27. 27. The Importance of Adherence <ul><li>Only 1/2 to 2/3 of patients take at least 75% of prescribed antihypertensive medicines 1 </li></ul><ul><ul><li>Of those taking < 75%, only 37% achieved BP goal </li></ul></ul><ul><ul><li>Of those taking ≥ 75%, 81% achieved goal </li></ul></ul><ul><li>In a recent BMJ study, the same rate of adherence was found in both responsive and resistant patients (82%) 2 </li></ul><ul><ul><ul><li>1. Arch Int Med 1987; 147:1393-1396 </li></ul></ul></ul><ul><ul><ul><li>2. BMJ 2001; 323:142 </li></ul></ul></ul>
    28. 28. Techniques to Improve Adherence <ul><li>Education of the patient </li></ul><ul><ul><li>Increases awareness but less effect on behavior </li></ul></ul><ul><li>Minimize the number of pills </li></ul><ul><ul><li>Combination pills (ACEI/Diuretic, ARB/Diuretic, ARB/Ca-blocker, etc.) </li></ul></ul><ul><li>Increase the frequency of visits </li></ul><ul><ul><li>Use of care managers </li></ul></ul>
    29. 29. Approach to Resistant Hypertension <ul><li>Establish “true resistance” </li></ul><ul><ul><li>Measure BP accurately </li></ul></ul><ul><ul><li>Consider “White Coat Hypertension” </li></ul></ul><ul><ul><li>Consider “Pseudoresistance” </li></ul></ul><ul><ul><li>Medication Adherence </li></ul></ul><ul><ul><li>Consider secondary causes </li></ul></ul>
    30. 30. Secondary Causes of Hypertension <ul><li>Obstructive Sleep Apnea </li></ul><ul><li>Obesity (Metabolic Syndrome) </li></ul><ul><li>Endocrinopathies </li></ul><ul><ul><li>Hyperaldosteronism, thyroid problems, pheochromocytoma </li></ul></ul><ul><li>Kidney Disease </li></ul><ul><ul><li>Renal Insufficiency and Renal Artery Stenosis </li></ul></ul>
    31. 31. Management of Refractory Hypertension
    32. 32. Management of Refractory Hypertension - 1 <ul><li>The therapeutic outline should be optimized with the different classes of antihypertensives, including the use of a diuretic in adequate therapeutic doses. </li></ul><ul><li>Two different strategies can be used in the attempt of finding an appropriate therapeutic outline for each patient, besides basing it on pathophysiologic knowledge: </li></ul><ul><li>1) The empiric approach based on the systematic changes of antihypertensive drugs with the use of associations of two, three or four different pharmacological classes together with adequate dose of thiazide diuretics. </li></ul><ul><li>The use of loop diuretics follows the same orientation applied to hypertension of other degrees. </li></ul><ul><li>2) The rational approach considering the hemodynamic profile and the levels of activity of plasma renin allows to divide this group of patients into volume-dependent and renin-dependent, making it possible to better choose the antihypertensive for each subgroup. </li></ul><ul><li>Prevalence of high hyperactivity found in young hypertensive patients and elevation of the levels of activity of renin guide the preferential use of beta-blockers in association with thiazides. </li></ul>N Engl J Med. 2001;344(1):3-10, Med. 2000;107(5):57-70.
    33. 33. Management of Refractory Hypertension - II <ul><li>If available, the quantification of plasma renin can address the treatment with drugs. </li></ul><ul><li>If the patient presents high plasma renin activity (>0.65 ng/mL/h), the treatment begins with angiotensin converting enzyme (ACEI), AT1 angiotensin II receptor blockers and beta-blockers. </li></ul><ul><li>If the plasma renin activity becomes low (<0.65 ng/mL/h), the patient is classified as volume-dependent and should be treated preferentially with a diuretic and calcium channels blockers. </li></ul>
    34. 34. Management of Refractory Hypertension - III <ul><li>Central nervous alpha-blockers (prazosin, doxazosin, alpha-metildopa and clonidine), direct vasodilators (hydralazine and minoxidil) may be used in resistant hypertension when association with other drugs fails. </li></ul><ul><li>In patients with high plasma aldosterone, the associated use of mineralocorticoid antagonists (spironolactone and eplerenone) can be effective to reduce the blood pressure besides delaying the structural alterations that characterize the cardiovascular remodeling. </li></ul>
    35. 35. Study performed at Mayo Clinics with Refractory Hypertensive patients <ul><li>A study performed at Mayo Clinics (US) with 104 refractory hypertensive patients demonstrated that there was a control of blood pressure and reduction in vascular resistance when the pharmacological treatment was based on hemodynamic non-invasive measurements (thoracic bioimpedance) when compared with the empiric choice of classes of antihypertensives and adjustments of doses to the specialist's criterion regarding arterial hypertension. </li></ul><ul><li>Hypertension. 2002;39(5):982-8. </li></ul>
    36. 36. Thank You