Hypertension and Dyslipidemia An ominous—and common—combination

1. Hypertension and DyslipidemiaAn ominous—and common—combination NED FERGUSON, M.D. March 2004

3. NCEP ATP IIIMetabolic Syndrome Criteria *Diagnosis is established when > 3 of these risk factors are present †Abdominal obesity is more highly correlated with metabolic risk factors than is BMI ‡Some men develop metabolic risk factors when circumference is only marginally increased Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA. 2001;285:2486-2497.

4. Key Challenges Overview: Summary • Obesity is significant risk factor for several interrelated conditions • Hypertension • Dyslipidemia • Diabetes • Atherosclerosis • Even relatively low levels of elevated blood pressure and lipids impart significant increased CVD risk • Hypertension and dyslipidemia often occur concomitantly • Concomitant hypertension and dyslipidemia increase CVD risk exponentially

5. Statement of Need The scope: • Concomitant hypertension and dyslipidemia occurs more commonly than would be expected in the general population • 1 in 4 American adults have hypertension • ~40% of US adults have total serum cholesterol levels > 200 mg/dL • Framingham data showed ~50% of men and women who presented with treatable hypertension also had an abnormal lipid profile The problem: • ~27 million Americans have both hypertension and dyslipidemia • Only ~9 million have been diagnosed with both • Only ~3 million are being treated for both The need: • When 1 condition is diagnosed, check for the other • If both are detected, treat maximally to decrease CVD risk and events

6. A Growing Need • More Americans than ever before could benefit from treatment of hypertension and dyslipidemia • The graying of the population • More-aggressive guidelines JNC 7 and NCEP ATP III • The weight of the evidence • The evidence of the weight national epidemic of obesity

7. JNC 7More-Aggressive Guidelines

8. OVERCOMING CLINICAL INERTIA TO CONTROL HYPERTENSION • Importance of systolic BP-explain seriousness and urgency for treatment to patients • Need for multiple drugs is common-due to progression of disease, not failure of care • “Mild” elevation of BP is not “mild”-patients will suffer if this is not treated

9. ATP IIIMore-Aggressive Guidelines NCEP ATP III. JAMA. 2001;285:2486.

10. Six Stages of Medication Adherence • Stage 4: “You are ill. Take this medicine until you feel well, and continue for a lifetime of therapy, even if you never again feel ill.” • Stage 5: “You are well. Take this medicine every day for the rest of your life to prevent illness.” Courtesy: Ockene IS.

11. Six Stages of Medication Adherence • Stage 6: “You are well. Take this medicine, which may make you feel sick, will be expensive, and will constantly remind you that you have a ‘problem,’ every day for the rest of your life to prevent an illness that is unlikely to occur for many years, and that may never occur even if you don’t take the medication.” Courtesy: Ockene IS.

12. Adherence to Antihypertensive and Lipid-Lowering Therapy Over Time • Only about 1 in 3 patients was classified as adherent to concomitant antihypertensive and lipid-lowering therapy over time. • Another third was not adherent with either therapy in each interval. • Remainder of the population (25%-30%) was adherent with one medication (usually antihypertensive therapy) but not the other. • Adherence was better when therapies were initiated on or about the same date (within 0-30 days of each other). Chapman RH, et al. American Heart Association. 2003.

13. Nonadherence to Therapy: A Major Challenge • Nonadherence (aka noncompliance, nonpersistance, etc.) is a major problem • Within 1 year, ~50% of patients overall discontinue use of drugs • An additional ~35% discontinue treatment within 2 years National Council on Patient Information and Education, 1997.

14. Consequences of Nonadherence • Because of improper use, 30%-50% of prescriptions fail to produce desired therapeutic results • Nonadherence causes unnecessary hospital admissions costing $25 billion annually in the US National Council on Patient Information and Education. Berg JS, et al. Ann Pharmacother. 1993;27:S1-24.

15. Physician Adherence Management • “How do you remember to take your medicine?” • “As is the case with many patients, do you ever miss or forget a dose?” • “How do you remember to take your medication on weekends or while traveling?” • “What do you think you could do to avoid missing doses?” • “Might any future events interfere with taking your medication?” Clinician uses problem-solving approach based on questioning the patient in a nonjudgemental manner Insull W. J Intern Med. 1997;241:317.

18. Concomitant Hypertension/Dyslipidemia: Key Management Principles • Individualize care based on specific needs, but avoid unduly prioritizing treatment of 1 condition over the other • Educate patients about CVD risk reduction • Simultaneous blood pressure control and lipid-lowering through TLC • Employ treatment approaches that facilitate long-term adherence by considering real-world issues • Drug cost • Dosing schedules • Number of pills taken per day • Adverse effects • Regularly update patients on current numbers and goals for both blood pressure and lipids • Explain significance of numbers • Record goal in chart to prompt follow-up at each visit

19. JNC 7Thorough Hypertension Evaluation • Physical examination • Appropriate measurement of BP, verified in contralateral arm • Optic fundi examination • BMI calculation • Auscultation for carotid, abdominal, femoral bruits • Thorough examination of heart and lungs • Examination of abdomen for enlarged kidneys, masses, abnormal aortic pulsation • Palpation of lower extremities for edema, pulses • Neurological assessment Chobanian AV, et al. JAMA. 2003;289:2560-2572.

20. JNC 7Lifestyle Modifications • Healthy lifestyle is critical for hypertension management • Reduces BP • Enhances antihypertensive drug efficacy • Decreases CVD risk • DASH diet (1600 mg sodium/d) may be as efficacious as single-drug therapy • Combinations of > 2 modifications can achieve even better results Chobanian AV, et al. JAMA. 2003;289:2560-2572.

21. DASH StudyEffects of Diet onSystolic and Diastolic Blood Pressure • Dietary Approaches to Stop Hypertension • 459 adults with mild hypertension or high-normal blood pressure (<160/80-95) randomized for 8 weeks to: • Control diet or • High fruit/vegetable diet or • DASH combination diet (high fruit/vegetable, low saturated fat and cholesterol, high calcium, high potassium) • Sodium intake and body weight remained constant Appel LJ, et al. N Engl J Med. 1997;336:1117-1124.

22. JNC 7Combination Therapy • Most patients require > 2 drugs to achieve goals • If blood pressure > 20/10 mmHg above goal, consider initiating treatment with 2 drugs • Separate prescriptions, or fixed-dose combinations • Using lower-than standard doses of > 2 drugs may improve efficacy and reduce adverse effects • Use caution in patients at risk for orthostatic hypotension • Diabetes • Autonomic dysfunction • Older patients Chobanian AV, et al. JAMA. 2003;289:2560-2572. Law MR, et al. BMJ. 2003;326:1427-1434.

24. How Low Should LDL-Cholesterol Be? New Guidelines are Needed BRITISH HEART PROTECTION STUDY: Simvastatin 40 mg reduces risk of CV events by 30% even in patients with initial untreated LDL-C < 100 mg/dL ARBITER: Regression of carotid atherosclerosis as measured by carotid artery intima-media thickness is directly related to the absolute LDL-C level obtained on statin therapy. The greatest regression occurred with an LDL-C < 70 mg/dL.

25. REVERSAL: The effect of 18 months of intensive LDL-C lowering therapy with atorvastatin (46% reduction from baseline) was compared with more moderate therapy with pravastatin (25% from baseline), in CHD patients. The intensive LDL-C lowering regimen halted the progression of atherosclerosis as measured by total plaque volume using intravascular ultrasound (IVUS).

26. ASCOT: In treated hypotensive patients, at moderate risk for CV events and with average baseline LDL-C of 130 mg/dL, 10 mg atorvastatin reduced all CV events and stroke by 21-36% compared with placebo. This effect emerged early and led to early termination of the lipid-lowering arm of the study. Final LDL-C on therapy was 84 mg/dL.

28. Events * in the Major Prevention Trials

29. Low HDL Cholesterol Postprandial Hyperlipidemia Small, Dense LDL    HYPERTRIGLYCERIDEMIA    Triglyceride-Rich Lipoprotein Remnants Procoagulant State Insulin Resistance Figure 2. Association of elevated serum trigylceride levels and atherogenic risk factors. Modified from Brewer HB Jr. Hypertriglyceridemia: changes in the plasma lipoproteins associated with an increased risk of cardiovascular disease. Am J Cardiol 1999;83:3F-12F, with permission from Excerpta Medica Inc.

30. Lowering LDL-C Is Not Enough Despite significant lowering of LDL-C in the statin trials, over 65% of treated patients continue to have, or die from, CV events. Most patients with atherosclerotic disease have a mixed dyslipidemia with elevated LDL-C, but as importantly, elevated triglycerides and low levels of HDL-C.

31. This atherogenic lipid profile is characterized by small, dense LDL lipoprotein particles and low levels of large, protective HDL particles. It appears that “ideal lipid goals” for high risk patients need to be lower than published guidelines and prudent and safe recommendations are: