HTN and Dyslipidemia.pptx - RussoCME - Primary Care Medical ...
How to Succeed atHypertension without really trying Or how to normalize CAD Risk in Most ofYour Patients with Essential HypertensionThomas E. Richtsmeier MD FACC Wenatchee Valley Medical Center Moses Lake Clinic Slide Source: Lipids Online Slide Library www.lipidsonline.org
What I propose to do in the next hour Put Atherosclerosis in context of RISK FACTORS, especially HTN & DYSLIPIDEMIA. Review the pathobiology of HTN, HTN Tx/Rx, and how to design effective, well tolerated, and affordable therapy Review the pathobioloby of DYSLIPIDEMIA, lipid lowering Tx/Rx, and how to design well tolerated, and affordable therapy This hour can not cover all the details; familiarize yourself with good reviews [JNC 7/8, NCEP 3/4] Slide Source: Lipids Online Slide Library www.lipidsonline.org
National Heart, Lung, and Blood Institute National High Blood Pressure Education Program U.S. Department of The Seventh Report of the Health and Human Services Joint National Committee on Prevention, Detection, Evaluation, and Treatment of National Institutes High Blood Pressure (JNC 7) of Health NationalHeart, Lung, and Blood Institute Slide Source: Lipids Online Slide Library www.lipidsonline.org
New Features and Key Messages For persons over age 50, SBP is a more important than DBP as CVD risk factor. Starting at 115/75 mmHg, CVD risk doubles with each increment of 20/10 mmHg throughout the BP range. Persons who are normotensive at age 55 have a 90% lifetime risk for developing HTN. Those with SBP 120–139 mmHg or DBP 80–89 mmHg should be considered prehypertensive who require health-promoting lifestyle modifications to prevent CVD. Slide Source: Lipids Online Slide Library www.lipidsonline.org
HYPERTENSION AND CARDIOVASCULAR DISEASE RISK HTN prevalence ~ 50 million people in the United States. The BP relationship to risk of CVD is continuous, consistent, and independent of other risk factors. Each increment of 20/10 mmHg doubles the risk of CVD across the entire BP range starting from 115/75 mmHg. Prehypertension signals the need for increased education to reduce BP in order to prevent Slide Source: Lipids Online Slide Library www.lipidsonline.org
Blood Pressure ClassificationBP Classification SBP mmHg DBP mmHgNormal <120 and <80Prehypertension 120–139 or 80–89Stage 1 Hypertension 140–159 or 90–99Stage 2 Hypertension >160 or >100 Slide Source: Lipids Online Slide Library www.lipidsonline.org
Cardiovascular Mortality Risk Increases as Blood Pressure Rises* 8x 8 7CardiovascularMortality Risk 6 5 4x 4 3 2x 2 1 0 115/75 135/85 155/95 175/105 Systolic/Diastolic Blood Pressure (mm Hg)*Measurements taken in individuals aged 40–69 years, beginning with a blood pressure of 115/75 mm Hg.Lewington S, et al. Lancet. 2002;360:1903-1913; Slide Source:Chobanian AV, et al. JAMA. 2003;289:2560-2572. Lipids Online Slide Library www.lipidsonline.org
Impact of High-Normal Blood Pressure on Risk of Major Cardiovascular Events* in MenCumulative Incidence of Major 16 Blood Pressure: Cardiovascular Events (%) 14 High-Normal 130–139/85–89 mm Hg 12 10 Normal 120–129/80–84 mm Hg 8 6 Optimal <120/80 mm Hg 4 2 0 0 2 4 6 8 10 12 Time (Years)*Defined as death due to cardiovascular disease or as having recognized myocardial infarction, stroke, or congestive heart failure. Slide Source: Vasan RS. N Engl J Med. 2001;345:1291-1297. Lipids Online Slide Library www.lipidsonline.org
Relationship of Hypertension to Its Comorbidities Comorbidity Relationship to Hypertension 50% of patients with coronary artery disease Coronary artery disease have hypertension 15% to 20% of hypertensive adults have an Left ventricular hypertrophy increased left ventricular mass 77% of patients who have a first stroke have Ischemic stroke a blood pressure >140/90 mm Hg 8% to 15% of hypertensive adults have Chronic kidney disease decreased renal function 75% of added cardiovascular risk in diabetic Diabetes patients is attributable to hypertension 74% of patients with peripheral artery Peripheral artery disease disease have hypertensionDiamond JA, Phillips RA. Hypertens Res. 2005;28:191-202;El-Atat F,et al. Curr Hypertens Rep. 2004;6:215-223; Pepine CJ. Am J Cardiol.1998;82(3A):21H-24H; Rosamond W, et al. Circulation. 2007;115:69-171; Segura J, et al. Curr Opin Nephrol Hypertens. 2004;13:495-500;Selvin E, Erlinger P. Circulation. 2004;110:738-743. Slide Source: Lipids Online Slide Library www.lipidsonline.org
Prevalence of Hypertension in the United States by Age Group*Hypertension Prevalence † Age*Based on data from the 19992000 National Health and Nutrition Examination Survey. Hypertension is defined as blood pressure 140/90 mm Hg or as receiving antihypertensive treatment.†Low reliability due to large relative error. Slide Source:Fields LE, et al. Hypertension. 2004;44:398-404. Lipids Online Slide Library www.lipidsonline.org
The VA Cooperative Study, 1967: Assessable Morbid/Fatal Events Placeb Active [Tx:Hctz, Reserpine, Hydralaz] o Rx* n=70 n=73 Accelerated 12 0 hypertension Stroke 4 1 Coronary event 2 0 CHF 2 0 Renal damage 2 0 Deaths 4 0*P<0.001 active drug therapy vs placebo Slide Source: Lipids Online Slide LibraryVA Cooperative Study Group. JAMA. 1967;202:1028-1034. www.lipidsonline.org
Landmark Clinical TrialsHypertension Treatment and Cardiovascular Disease Outcomes 1967 – VA Cooperative Study on DBP 115-129 1970 – VA Cooperative Study on DBP 90-114 1979 – HDFP 1980 – Australian Trial, Oslo Trial 1985 – MRC I, EWPHE 1991 – SHEP, STOP-Hypertension 1992 – MRC II in the elderly 1997 – Syst-Eur 2002 – LIFE 2002 – ALLHAT Slide Source: Lipids Online Slide Library www.lipidsonline.org
Relative Risk for Stroke Odds ratios and 95% confidence intervals Veterans Administration, 1967 Veterans Administration, 1970 Hypertension Stroke Study, 1974 USPHS Study, 1977 EWPHE Study, 1985 Coope and Warrender, 1986 SHEP Study, 1991 STOP-Hypertension Study, 1991 MRC Study, 1992 Syst-Eur Study, 1997 0 0.5 1 1.5 2 Total 0.63(0.55 to 0.72) Active treatment Active treatment better than placebo worse than placeboReprinted from He J, et al. Am Heart J. 1999; Slide Source:138:211-219, with permission from Elsevier. Lipids Online Slide Library www.lipidsonline.org
Relative Risk for Coronary Heart Disease Odds ratios and 95% confidence intervals Veterans Administration, 1967 Veterans Administration, 1970 Hypertension Stroke Study, 1974 USPHS Study, 1977 EWPHE Study, 1985 Coope and Warrender, 1986 SHEP Study, 1991 STOP-Hypertension Study, 1991 MRC Study, 1992 0.79 (0.69 to 0.90) Syst-Eur Study, 1997 0 0. 1 1.5 2 Total Active treatment 5 Active treatment better than placebo worse than placebo Reprinted from He J, et al. Am Heart J. 1999; Slide Source: 138:211-219, with permission from Elsevier. Lipids Online Slide Library www.lipidsonline.org
Benefits of Lowering BP Average Percent ReductionStroke incidence 35–40%Myocardial infarction 20–25%Heart failure 50% Slide Source: Lipids Online Slide Library www.lipidsonline.org
Office BP Measurement Use auscultatory method with a properly calibrated and validated instrument. Patient should be seated quietly for 5 minutes in a chair (not on an exam table), feet on the floor, and arm supported at heart level. Appropriate-sized cuff should be used to ensure accuracy. At least two measurements should be made. Consider ABI Clinicians should provide to patients, verbally and in writing, specific BP numbers and BP goals. Slide Source: Lipids Online Slide Library www.lipidsonline.org
Patient EvaluationEvaluation of patients with documented HTN has three objectives:1. Assess lifestyle and identify other CV risk factors or concomitant disorders that affects prognosis and guides treatment.2. Reveal identifiable causes of high BP. [95-98 % will be “Essential”]3. Assess the presence or absence of target organ damage and CVD. Slide Source: Lipids Online Slide Library www.lipidsonline.org
Laboratory Tests Routine Tests • Electrocardiogram • Urinalysis • Blood glucose, and hematocrit • Serum potassium, creatinine, or the corresponding estimated GFR, and calcium • Lipid profile, after 9- to 12-hour fast, that includes high- density and low-density lipoprotein cholesterol, and triglycerides Optional tests • Measurement of urinary albumin excretion or albumin/creatinine ratio More extensive testing for identifiable causes is not generally indicated unless BP control is not achieved Slide Source: Lipids Online Slide Library www.lipidsonline.org
Easily Identifiable (“Primary”) Causes of Hypertension High Sodium Diet ………….[Use of salt shaker and convenience foods, high urinary sodium] Sleep apnea………………………….……..….[Obesity, typical Sx] Drug-induced or related causes………………[BCP, NSAIDs, etc] Chronic kidney disease ………...…..[CC< 60cc/min, Proteinuria] Primary aldosteronism ……………………..………[Hypokalemia] Reno vascular disease……..…. [Abdominal bruit in m.a. woman] Coarctation of the aorta…….. [Widened radial-pedal pulse inter- val; measure pedal systolic BP. ABI>1] Slide Source: Lipids Online Slide Library www.lipidsonline.org
Classification and Management of BP for adults Initial drug therapy BP SBP* DBP* Lifestyle classification mmHg mmHg modification Without compelling With compelling indication indicationsNormal <120 and <80 EncouragePrehypertension 120–139 or 80–89 Yes No antihypertensive drug Drug(s) for compelling indicated. indications. ‡Stage 1 140–159 or 90–99 Yes Thiazide-type diuretics for Drug(s) for theHypertension most. May consider ACEI, compelling ARB, BB, CCB, or indications.‡ combination. Other antihypertensiveStage 2 >160 or >100 Yes Two-drug combination for drugs (diuretics, ACEI,Hypertension most† (usually thiazide-type ARB, BB, CCB) as diuretic and ACEI or ARB or needed. BB or CCB). *Treatment determined by highest BP category. †Initial combined therapy should be used cautiously in those at risk for orthostatic hypotension. Slide Source: ‡Treat patients with chronic kidney disease or diabetes to BP goal of <130/80 mmHg. Lipids Online Slide Library www.lipidsonline.org
BP Measurement and Clinical Evaluation Classification of BP Tobacco CVD Risk [e.g. Framingham 10 year or 30 year RISK] Lipids DM BP Measurement Techniques FHx • In-office • Ambulatory BP Monitoring • Self-measurement Patient EvaluationLaboratory Tests and Other Diagnostic Procedures Patient Centered: Dx, Overall Risk, Education, and compact for care Slide Source: Lipids Online Slide Library www.lipidsonline.org
Microalbuminuria Compared To Traditional Risk Factors For Ischemic Heart Disease 3 N=2,085; 10 year follow-up 2.5 Relative Risk 2 1.5 1 l a g BP r o 0.5 de in i er ur ok ic en st in ol Sm e m G st ol bu e Ch Sy al al M al ro t ic To MBorch-Johnsen K, et al. Slide Source:Arterioscler Thromb Vasc Biol. 1999;19(8):1992-1997. Lipids Online Slide Library www.lipidsonline.org
Current Blood Pressure Targets for Various Chronic Conditions Systolic ≤140 Blood Uncomplicated Pressure Hypertension ≤90 Diastolic Blood Pressure Chronic Kidney ≤130 Disease Coronary Artery ≤80 Disease Diabetes mm HgAmerican Diabetes Association. Diabetes Care. 2003;26:S80-S82;Hansson L, et al. Lancet. 1998;351:1755-1762; National KidneyFoundation. Am J Kidney Dis. 2002;39(2 Suppl 1):S1-S266; Slide Source:Rosendorff C, et al. Circulation. 2007;115:2761-2788. Lipids Online Slide Library www.lipidsonline.org
Major Trials in Isolated Systolic Hypertension Agent N Age Entry BP (mm Hg) SHEP Diuretic BB 4736 60 171/77 Syst-Eur DHP CCB 4695 60 174/86 Stroke CHD CHF All CVD 0 Reduction (%) -10 Relative Risk -20 -30 -30 -29 -32 -31 -40 * -36 -33 -50 -42† -50 -60*P=0.0003; †P=0.003.BB=β-blocker; DHP CCB=dihydropyridine calcium channel blocker.SHEP Cooperative Research Group. JAMA. 1991;265:3255-3264; Staessen etal. Lancet. 1997;350:757-764; Kostis et al. JAMA. 1997;278:212-216. Source: Slide Lipids Online Slide Library www.lipidsonline.org
Goals of Therapy Reduce CVD and renal morbidity and mortality. Treat to BP <140/90 mmHg or BP <130/80 mmHg in patients with diabetes or chronic kidney disease. Achieve SBP goal especially in persons >50 years of age. However, do not lower Diastolic BP < 60 mmHg to protect Coronary Perfusion Slide Source: Lipids Online Slide Library www.lipidsonline.org
Recommended Lifestyle Modifications and Their Individual Effects on Blood Pressure Approximate Modifications* Recommendation SBP Reduction Maintain normal body weight Reduce weight 320 mm Hg (BMI of 18.524.9 kg/m2) Rich in fruit, vegetables, and Adopt DASH diet low-fat dairy; reduced saturated 814 mm Hg and total fat contentReduce dietary sodium <100 mmol (2.4 g)/day 28 mm Hg Increase physical Aerobic activity >30 min/day 49 mm Hg activity most days of the week Moderate alcohol Men: ≤ 2 drinks/day 24 mm Hg consumption Women: ≤ 1 drink/day *Combining 2 or more of these modifications may or may not have an additive effect on blood pressure reduction. SBP = systolic blood pressure; BMI = body mass index; DASH = Dietary Approaches to Stop Hypertension Chobanian AV, et al. JAMA. 2003;289:2560-2572; Slide Source: Lipids Online Slide Library Blumenthal JA, et al. Arch Intern Med. 2000;160:1947-1958. www.lipidsonline.org
Decreasing Dietary Salt Intake Reduces Systolic Blood Pressure Dietary Approaches to Stop Hypertension Trial 136 *Pressure (mm Hg) 134 Systolic Blood 132 * 130 * * 128 * 126 124 1 2 3 4 High-Salt Diet† Weeks on Low-Salt Diet‡ *Error bars represent standard deviation; †140 mmol/day; ‡62 mmol/day. Reprinted from Obarzanek E, et al. Hypertension. 2003;42: Slide Source: 459-467, with permission from Lippincott Williams & Wilkins. Lipids Online Slide Library www.lipidsonline.org
Cigarette Smoking: Recommendations GOAL Complete Cessation and No Exposure to Environmental Tobacco Smoke Ask about tobacco use status at every visit Advise every tobacco user to quit Assess the tobacco user’s willingness to quit NEVER GIVE l lla llb lll Assist by counseling and developing a plan UP HELPING for quitting B Arrange follow-up, referral to special THEM TO programs, or pharmacotherapy (including QUIT nicotine replacement and bupropion) Urge avoidance of exposure to environmental tobacco smoke at work and home Slide Source:Smith SC Jr et al. Circulation 2006;113:2363–2372. Lipids Online Slide Library www.lipidsonline.org
Antihypertensive Drug Classes: Action Sites Blood Pressure = Cardiac Output Total Peripheral Resistance -Blockers a--Blockers Antihypertensive ACE Inhibitors Drug Classes AT1 Blockers Direct renin inhibitors 1-Blockers Non-DHP 2-Agonists CCBs All CCBs Diuretics Diuretics Sympatholytics VasodilatorsACE = angiotensin-converting enzyme; AT1 = angiotensin type 1;CCBs = calcium channel blockers; DHP = dihydropyridine Slide Source: Lipids Online Slide Library www.lipidsonline.org
Average Number of Anti-Hypertensive Agents Used to Achieve Target BP MDRD ABCD HOT UKPDS <92 <75 <80 <85 Goal BP mmHg mmHg mmHg mmHg MAP* DBP DBP DBP Achieved 93 ~75 81 82 BP Avg # of drugs 3.6 2.7 3.3 2.8 per patient*The goal mean arterial pressure (MAP) of <92 mmHg specified in the MDRD trial correspondsto a systolic/diastolic blood pressure of approximately 125/75 mmHg. Slide Source: Lipids Online Slide Library www.lipidsonline.org
ALLHAT Medication Use and BP Control* 1 Drug 2 Drugs 3 Drugs ≥4 Drugs Average # 6 of Drugs 1 2 3 100% 4 2 6 14 1.8 22 18 # of Drugs/Patient 80% 27 1.6 Patients (%) 1.4 32 60% 36 1.2 1 40% 72 0.8 63 0.6 48 20% 37 0.4 0.2 0% 0 6 mon 1 yr 3 yr 5 yr ALLHAT = Antihypertensive Lipid-Lowering Treatment to Prevent Heart Attack Trial; BP = blood pressure *Percentage controlled to <140/90 mm Hg. Slide Source: Lipids Online Slide Library Cushman WC, et al. J Clin Hypertens. 2002;4:393-404. www.lipidsonline.org
Algorithm for Treatment of Hypertension Lifestyle Modifications Not at Goal Blood Pressure (<140/90 mmHg) (<130/80 mmHg for those with diabetes or chronic kidney disease) Initial Drug Choices Without Compelling With Compelling Indications Indications Stage 1 Hypertension Stage 2 Hypertension Drug(s) for the compelling(SBP 140–159 or DBP 90–99 mmHg) (SBP >160 or DBP >100 mmHg) indications Thiazide-type diuretics for most. 2-drug combination for most (usually Other antihypertensive drugs May consider ACEI, ARB, BB, CCB, thiazide-type diuretic and (diuretics, ACEI, ARB, BB, CCB) or combination. ACEI, or ARB, or BB, or CCB) as needed. Not at Goal Blood Pressure Optimize dosages or add additional drugs until goal blood pressure is achieved. Consider consultation with hypertension specialist. Slide Source: Lipids Online Slide Library www.lipidsonline.org
Step-wise therapy to control Essential Hypertension Outline DIET and LIFE-STYLE therapies that patient can reasonably begin and maintain. Encourage DASH diet and HBPM Begin Rx with ACE-I (e.g. LISINOPRIL 10-20 mg) or ARB (e.g. LOSARTAN 25-50 mg) or Diuretic (Chlorthalidone 12.5 mg) Add D-CCB (e.g. Amlodipine 5 mg) Slide Source: Lipids Online Slide Library www.lipidsonline.org
Escalating therapy in Essential Hypertension Next add low dose diuretic (e.g. Chlorthalidone 12.5-25 or HCTZ 12.5- 25 mg) Use loop diuretic if edema, CHF, or KKD present: (e.g. Furosemide 20-40 mg QD-BID) Next uptitrate ACE-I and/or D-CCB to full dose (e.g. Lisinopril 40 mg and Amlodipine 10 mg) Next add vasodilator-BB (e.g. Carvedilol 6.25 mg BID) Uptitrate all Rx to full dose and/or add Spironalactone Slide Source: Lipids Online Slide Library www.lipidsonline.org
Hypertension Control Rates AreSlowly Improving (NHANES Data) Adults (%) 1976 1988 1991 1999 2001 2003 2005 - - - - - - - 1980 1991 1994 2000 2002 2004 2006 *Controlled blood pressure was defined as <140/90 mm Hg and expressed as a % of all hypertensives. NHANES = National Health and Nutrition Examination Survey. Chobanian AV, et al. JAMA. 2003;289:2560- 2572; Ong KL, et al. Hypertension. 2007;49:69- Slide Source: 75; Ostchega Y, et al. NCHS Data Brief. Lipids Online Slide Library 2008;(3):1-8. www.lipidsonline.org
Monthly Cost of 4 Drug Therapy BASED ON GENERIC DRUGS AT DISCOUNT PHARMACIES FOR 30 DAYS OF THERAPY Diet and life style…………………….… ….….…$0.00 Chlorthalidone 25 mg QD………… ….….….$3.00 Lisinopril 40 mg QD…………………….....…...$6.00 Amlodipine 10 mg ½ QD……… …..........$14.00 Carvedilol 25 mg ½ BID……………….....….$3.00 TOTAL COST FOR 1 MONTH Rx....$26.00 Slide Source: Lipids Online Slide Library www.lipidsonline.org
Causes of Resistant Hypertension1. Excess dietary sodium intake (Diet must be < 2 Grams Sodium)2. Medication prescription issues a. Inadequate diuretic therapy b. Inadequate doses of vasodilator meds c. Drug actions and interactions (e.g., nonsteroidal anti-inflamm. drugs (NSAIDs), cocaine, sympathomimetics, oral contraceptives) d. Non-adherence (Not refilling Rx or not taking Rx)3. Excessive alcohol intake (Often >5 oz/day)4. Obesity, esp. Abnormal Sleep Breathing/Obstructive Sleep Apnea5. Primary causes of HTN (KKD, B RAS, Pheo, Aldost, Coarct, etc) Circulation 2008;117:e510-526 Slide Source: Lipids Online Slide Library www.lipidsonline.org
How to Succeed at Treating Dyslipidemia without really trying Or how to normalize CAD Risk in Most of Your PatientsThomas E. Richtsmeier MD FACC Wenatchee Valley Medical Center Moses Lake Clinic Slide Source: Lipids Online Slide Library www.lipidsonline.org
National Cholesterol Education Program Adult Treatment Panel III and Update (ATP III) Guidelines
NCEP III: Update 2004NCEP III 2001 JAMA 2001 285:2486-975 New Clinical Trials MRC HPS*, PROSPER, ALLHAT-LLT, ASCOT-LLA*, PROVE IT*. 2 Additional Trials: REVERSAL*, CARDSConfirmation of “CAD Risk Equivalents” including Type 2 Diabetes and Continued emphasis on the Metabolic Syndrome.New LDL Goal for “very high risk patients” LDL-C goal < 70 mg/dL, or Non-HDL < 100 mg/dL and LDL lowering of at least 30% Circulation 2004; 110:227-39 Or www.nhlbi.nih.gov/guidelines/cholesterol
& ORIGIN OF BLOOD LIPIDSTriglyceridesSaturated Fat CHOLESTEROL IS ESSENTIAL FOR LIFE Slide Source: Lipids Online Slide Library www.lipidsonline.org
Risk Factors for CHD MODIFIABLE NON-MODIFIABLE– DYSLIPIDEMIA* • AGE Elevated LDL* • SEX Low HDL • FAMILY HISTORY of Raised TGs (esp. Premature CAD remnants)– SMOKING*– HYPERTENSION* HIGHEST RISK:– DIABETES MELLITUS* PRESENCE OF ASCVD– Novel Risk Factors: Alb-uria CAD, CVD, PAD hs-CRP, Metabolic Syndrome Indicates more rigorous– Thrombogenic factors Secondary Prevention– Sedentary lifestyleWood D, et al. Atherosclerosis. 1998;140:199-270. & TR. Slide Source: Lipids Online Slide Library www.lipidsonline.org
Initiation of Atherosclerosis Endothelium Healthy Endothelium Function: • Vasodilatory n • Non-Thrombogenic • Non-Adhesive of Mono. and Plat. Slide Source: Lipids Online Slide Library www.lipidsonline.org
Atherosclerosis Is an Inflammatory Disease L-Selectin, Monocyte Integrins VCAM- LDL E-Selectin, 1, P-Selectin ICAM-1 MCP-1 Intima OxLDL M-CSF Other Macrophage inflammator Activation & Division y triggers Media Smooth Muscle Cell Migration Slide Source:Libby et al. Circulation 2002;105:1135-1143. Lipids Online Slide Library www.lipidsonline.org
Characteristics of Plaques Prone to Rupture Fibrous cap Media Lipid Lumen core area of detail “Vulnerable” plaque Lume – T lymphocyte n Lipid – Macrophage core foam cell (tissue factor+) – “Activated” intimal SMC (HLA-DR+) – Normal medial SMC “Stable” plaqueLibby P. Circulation. 1995;91:2844-2850.
59 ATP III Lipid andLipoprotein ClassificationLDL Cholesterol (mg/dL)50-70…………Normal in all mammals70-100………..“Normal,” Optimal100–129………Near optimal130–159………Borderline high160–189………High190…………...Very high
Classification of Serum Triglycerides Triglyceride ATP III ATP II Levels Category Levels Normal <200 mg/dL <150 mg/dL 200–399 150–199 Borderline-high mg/dL mg/dL 400–1000 200–499 High mg/dL mg/dL Very high >1000 mg/dL 500 mg/dLExpert Panel on Detection, Evaluation, and Treatment of High BloodCholesterol in Adults. JAMA 1993;269:3015-3023. | Expert Panel onDetection, Evaluation, and Treatment of High Blood Cholesterol in Adults.JAMA 2001;285:2486-2497. Slide Source: Lipids Online Slide Library www.lipidsonline.org
61 HDL-C ATP III Lipid andLipoprotein Classification (continued)• HDL Cholesterol (mg/dL) <40 = Low 60 = High• HDL>60 is a negative risk factor.• Non-HDL Cholesterol is 2nd target for Tx. Example: T-C=200 HDL-C=50 NonHDL-C=150• T-Chol/HDL ratio remains the single• best predictor of risk on lipid profile Example: T-C=200 HDL-C=50 T-C/HDL= 4
Atherogenic Lipoproteins Non-HDL-Cholesterol = TC – HDL-C Total=VLDL + LDL+ OxLDL+IDL +Remnants Can be accurately measured in nonfasting state Apo B concentration represents total number of lipoprotein particles (LDL + IDL + VLDL) This may be called the “atherogenic cholesterol” Goal Non-HDL-C < 130 or High Risk Pts <100 Slide Source: Grundy SM. Circulation 1997;95:1-4. Lipids Online Slide Library www.lipidsonline.org
CHOOSING THERAPY GOALS RISK ASSESSMENT in Primary Prevention TO DEFINE CAD RISK AND ASSESS FOR Rx: USE FRAMINGHAM RISK . * * * * * * ** * * *Framingham Heart Study 10 year CAD risk. <10% Low. 10-20% Intermediate. >20% High
hs-CRP Adds to Predictive Value of TC:HDL Ratio in Risk of First MI 5.0 4.0 3.0 2.0 1.0 High 0.0 Medium High Medium Low Low hs-CRP Total Cholesterol:HDL Ratio Slide Source:Ridker PM et al. Circulation 1998;97:2007-2011. Lipids Online Slide Library1998 Lippincott Williams & Wilkins. www.lipidsonline.org
67 ATP III CHD Risk Equivalents• Patients with Clinical Coronary Artery Disease (MI, PCI, Angina, etc) have a 10 year risk >20 % MACE• Other clinical forms of atherosclerotic disease (peripheral arterial disease, abdominal aortic aneurysm, and symptomatic carotid artery disease)• Diabetes Mellitus• Multiple risk factors that confer a 10-year risk for CHD >20%• THIS MANDATES MORE AGGRESSIVE TX
Framingham 69 Study 3.0 2.0 Risk of CHD FUTUREafter 4 Years* 1.0 25 45 65 HDL-C 0.0 85 (mg/dL) 100 160 220 LDL-C (mg/dL)*Risk of coronary heart disease (CHD) over 4 years of follow-up for men ages 50 to 70Reprinted in adapted form from Castelli WP. Can J Cardiol.1988;4(Suppl A):5A–10A, with permission from Pulsus Group Inc.
DIET AND LIFESTYLE THERAPYIs The CORNERSTONE for ALL PATIENTS. DIETARY THERAPY TO PREVENT CAD: WHICH ONE?? ADA? AHA? ATKINS? LOW CARB? LOW GLYCEMIC INDEX FOODS? WHATEVER? THE DIET DELEMMMA: FINDING A RATIONAL RESOLTION Simple Non-expensive, 100 to150 minutes/wk Tasty Efficacious
Dietary Adjuncts TLC for patients with LDL-C = 160 Dietary Component LDL-C (mg/dL) Low saturated fat/dietary –12 cholesterol Viscous fiber (10–25 g/d) –8 Plant stanols/sterols (2 g/d) –16 Total –36Walden CE, et al. Arterioscler Thromb Vasc Biol. 1997;17:375-382.Jenkins DJ, et al. Curr Opin Lipidol. 2000;11:49-56. Slide Source:Cato N. Stanol meta-analysis. Personal communication, 2000. Lipids Online Slide Library www.lipidsonline.org
Cigarette Smoking:Recommendations GOAL Complete Cessation and No Exposure to Environmental Tobacco Smoke Ask about tobacco use status at every visit Advise every tobacco user to quit Assess the tobacco user’s willingness to quit l lla llb lll Assist by counseling and developing a plan Try to get for quitting B everyone Arrange follow-up, referral to special programs, or pharmacotherapy (including to quit. nicotine replacement and bupropion) Urge avoidance of exposure to environmental tobacco smoke at work and home Slide Source:Smith SC Jr et al. Circulation 2006;113:2363–2372. Lipids Online Slide Library www.lipidsonline.org
Physical Activity: Recommendations GOAL 30 minutes/day, 7 days/week; Minimum 5 days/week l lla llb lll Almost every Assess risk with a physical activity history B one can walk, and/or an exercise test, to guide prescription even if its only to shop at Walmart. lll l lla llb Encourage 30 to 60 minutes of moderate intensity aerobic activity such as brisk B Park your car as far from the walking, on most, preferably all days of the week, supplemented by an increase in daily entrance as lifestyle activities possible. These alone l lla llb lll will count as Advise medically supervised programs for B 20 minutes. high-risk patients (e.g. recent acute coronary syndrome or revascularization, HF) Slide Source:Smith SC Jr et al. Circulation 2006;113:2363–2372. Lipids Online Slide Library www.lipidsonline.org
Cholesterol Management Pharmacotherapy Patient Therapy TC LDL-C HDL-C TG tolerabilityStatins* 19 – 37% 25 – 50% 4 – 12% 14 – 29% GoodEzetimibe 13% 18% 1% 9% GoodBile acid 7 – 10% 10 – 18% 3% Neutral or Poorsequestrants Nicotinic acid 10 – 20% 10 – 20% 14 – 35% 30 – 70% Reasonable to poorFibrates 19% 4 – 8% 11 – 13% 30% GoodTC = Total cholesterol, LDL-C = Low-density lipoprotein cholesterol, HDL-C = High-density lipoprotein cholesterol, TG = Triglycerides*Daily dose of 40 mg of each drug, excluding rosuvastatinYeshurun D et al. South Med J 1995;88:379–391. | NCEP. Circulation 1994;89:1333–1445. | Knopp RH. N Engl J Med 1999;341:498–511. | Gupta EK et al. Heart Dis Slide Source:2002;4:399–409. Lipids Online Slide Library www.lipidsonline.org
75 Simvastatin Reduced the Risk of Major Coronary Events: Subgroup Analyses from the Scandinavian Simvastatin Survival Study n=1814 n=407 n=1156 n=542 n=573 n=105 0Percent Risk Reduction -10 -20 -30 -31 -34 -35 -34 -40 P<0.00001 P=0.01 P<0.0005 P<0.002 -37 P<0.002 -50 -55 -60 P=0.002 -70 Men Women Older Smokers Hyper- Diabetes tension 4S Group. Lancet 1994;334:1383–1389.
Majority of LDL-C Lowering Occursat the Lowest Statin Dose Atorvastatin Simvastatin 10/20/40/80 mg 10/20/40 mg† Daily Dose 211 mg/dl* 219 mg/dl* 0% -10% 28% 10 mg 38% -20% 20 mg -30% 35% 40 mg 13% 41% -40% 46% 80 mg 16% with -50% 51% 3 titrations 54% -60%*Mean baseline LDL-C.†At the time of this study, the maximum dose for simvastatin was 40 mg. Slide Source:Adapted from Jones P et al. Am J Cardiol 1998;81:582-587. Lipids Online Slide Library www.lipidsonline.org
80 HMG-CoA Reductase Inhibitor: Secondary Prevention Relationship between LDL-C Levels and Event Rates in Secondary Prevention Trials of Patients with Stable CHD 30 Statin 4S 25 Placebo 4S 20Event (%) 15 LIPID LIPID CARE CARE 10 HPS HPS TNT (atorvastatin 10 mg/d) 5 TNT (atorvastatin 80 mg/d) 0 3 70 90 110 130 150 170 190 210 LDL-C (mg/dL) LDL-C=low-density lipoprotein cholesterol; CHD=coronary heart disease; TNT=Treating to New Targets; HPS=Heart Protection Study; CARE=Cholesterol and Recurrent Events Trial; LIPID=Long-term Intervention with Pravastatin in Ischaemic Disease; 4S=Scandinavian Simvastatin Survival Study. LaRosa et al. N Engl J Med 2005;352:1425–1435.
Components of Secondary Prevention • Cigarette smoking cessation • Blood pressure control • Lipid management to goal • Physical activity • Weight management to goal • Diabetes management to goal • Antiplatelet agents / anticoagulants • Renin angiotensin aldosterone system blockers • Beta blockers • Influenza vaccination Slide Source:Smith SC Jr et al. Circulation 2006;113:2363–2372. Lipids Online Slide Library www.lipidsonline.org
Limitations of Statin Monotherapyon CHD Events Events,* n Events Risk not Control Statin Reduction, Avoided,Trial Drug N Group Group %† %4S Simvastatin 30,817 2,042 1,490 26 74WOSCOPS PravastatinCARE PravastatinAFCAPS LovastatinLIPID PravastatinHPS Simvastatin 20,586 1,212 898 26 74PROSPER Pravastatin 5,804 356 292 19 81ASCOT-LLA Atorvastatin 10,305 154 100 36 64Total 67,462 3,764 2,780 27 73* Nonfatal MI and CHD death; AFCAPS also included unstable angina† Weighted averageReprinted from Bays H. Expert Rev Cardiovasc Ther 2004; Slide Source:2:89-105, with permissions from Future Science Group. Lipids Online Slide Library www.lipidsonline.org
84 Combined Dyslipidemias:Low HDL & Elevated Triglycerides Non-HDL Cholesterol: Secondary Target • Primary target of therapy: LDL cholesterol Try to achieve LDL goal before treating non-HDL cholesterol • Therapeutic approaches to elevated non-HDL cholesterol – Intensify therapeutic lifestyle changes – Intensify LDL-lowering drug therapy – Nicotinic acid or fibrate therapy to lower VLDL
Combination Lipid-Altering Drug Therapy with StatinsNeed for combination lipid-alteringdrug therapy To achieve ATP III goals. Ezetimibe and statins Bile acid sequestrants and statins PPAR agonists and statins Fish oils and statins Niacin and statins Investigational lipid-altering drug combinations (CETP inhibition) Slide Source: Lipids Online Slide Library www.lipidsonline.org
86 Lipid Monotherapy Options: Clinical and Lipid Expectations CV Event Reduction LDL-C Decrease HDL-C Increase TG Decrease LDL Size/ Drug Class (%) (%) (%) (%) Buoyancy Statins 25% - 35% ++++ + + + (4S, CARE, 5% LIPID) Niacin 16% - 35% ++ ++++ ++++ +++ (CDP, 30% Stockholm) Fibrates 11% - 24% + ++ ++++ + (FIELD, 10% VA-HIT) Torcetrapib 61% + ++++ + + (??????) 40%CV=cardiovascular; LDL-C=low-density lipoprotein cholesterol; HDL-C=high-densitylipoprotein cholesterol; TG=triglycerideCompiled by Brown BG, December 2006.
Combination Niacin Extended-Release/Lovastatin vs Monotherapy withAtorvastatin or Simvastatin Percent Change from Baseline Week 8 Week 12 Niacin ER/L Niacin ER/L 1000/40 mg A 10 mg 1000/40 mg S 20 mg LDL-C –39%* –38% –42%* –35% HDL-C +20%** +3% +19%** +8% Triglyceride –30%** –20% –36%** –15% Lipoprotein(a) –16%** +5% –20%** –1%*P<0.01 versus simvastatin**P<0.001 versus atorvastatin and simvastatin Slide Source:Bays H et al. Am J Cardiol 2003;91:667-672. Lipids Online Slide Library www.lipidsonline.org
88 Angiographic Effects of Lipid Drug Classes Meta-Analysis, 12 Trials 4Change from Baseline in Mean Placebo (6) Proximal % Stenosis (%S) 3 Fibrates (1) Statins (6) Statin+Resin (1) 2 Niacin Combos (4) 1 Progression 0 Regression -1 -2 0 25 50 75 % Change in LDL-C in Rx (%) Placebo-Adjusted Compiled by Brown BG, August 2006.
STATIN and NIACIN CombinationNEJM 2001. 345:1583-92. 160 pts with CAD and low HDL and WNL LDL. Angiogr. Regression occurred only in Sim + Niacin pts
HDL-Atherosclerosis Treatment Study (HATS)Niacin and Statin Outcome Trial 89% *P<.05 25 23.7 Reduction vs Placebo 21.4 20 14.3 15 10 5 2.6* 0 Placebo S+N AV S + N + AV Coronary Death, MI, Stroke, or Revascularization Slide Source:Brown BG et al. N Engl J Med 2001;345:1583-1592. Lipids Online Slide Library www.lipidsonline.org
ASSESSING LIPID THERAPY AFTER ADEQUATE STATIN Tx. Is patient on high dose Is patient’s glycemic Is glycemic therapy adequate? BB or diuretic or smoking? control adequate? Is patient on TZD or Metformin? Can patient exercise? Is pt on TZD or Metformin? # * Lower dietary carb. and Saturated fats. Fibrate is Rx of choice for Trig> 500.# Each doubling of statin dose lowers LDL by about 6%.
92 Summary: Niacin plus Statin• Exceeds statin effects on LDL, HDL, TG, and LDL particle size/density• Stops stenosis progression in its tracks (small regression)• Magnitude of benefits predicted by epidemiology, (% HDL-C and % LDL-C change), and supported by 23- trial meta-analysis• Clinical proof: “AIM HIGH” trial release 2011 or 2012LDL=low-density lipoprotein; HDL=high-density lipoprotein; TG=triglyceride; HDL-C=high-density lipoprotein cholesterol; LDL-C=low-density lipoprotein cholesterol
93HOW TO USE STATIN & NIACIN VARIETIES ADMINISTRATION• Niacin XR-Lovastatin 1. Start Niacin XR 500 mg Niacin XR-Simvastatin with ASA 81 and Statin Advicor, Simcor with supper or H.S. 2. Slowly titrate to goal• Any Statin with OTC Do not exceed 2000mg Niacin XR (“SloNiacin”) Niacin XR• Any Statin with Niaspan 3. Monitor FBS, LFTs, Pyrosis, flushing , gout
Bile Acid Sequestrants:Colesevelam and Statins Colesevelam TC LDL-C HDL-C TG HCl Statin (%) (%) (%) (%) 0 mg Atorvastatin –43 –56 +2 –43 (no tablets) 80 mg 3750 mg Atorvastatin –35 –51 +7 –11 (6 tablets) 10 mgBays H et al. Expert Opin Pharmacother 2003;4:779-790. Slide Source:Hunninghake D et al. Atherosclerosis 2001;158:407-416. Lipids Online Slide Library www.lipidsonline.org
Incidence of MI during a 7-YearFollow-up in a Finnish Population 50 45.0 40 P<0.001 30 18.8 20.2 20 P<0.001 10 3.5 0 Prior MI No prior MI Prior MI No prior MI Nondiabetic subjects Diabetic subjects (n=1373) (n=1059) Slide Source:Haffner SM et al. N Engl J Med 1998;339:229-234. Lipids Online Slide Library www.lipidsonline.org
Atherosclerosis in Diabetes~80% of all diabetic mortality – 75% from coronary atherosclerosis and/or CHF – 25% from cerebral or peripheral vascular disease>75% of all hospitalizations for diabeticcomplications>50% of patients with newly diagnosedtype 2 diabetes have CHDMost common cause of ESRD and Blindness which are micro-vascular diseases.DM-2 is as much or more a Vascular Disease as a Metabolic Disease.National Diabetes Data Group. Diabetes in America. 2nd ed. NIH;1995 & TR
Stepwise Selection of Risk Factors* in 2693 White Patientswith Type 2 Diabetes with Dependent Variable as Time to First Event: UKPDS Coronary Artery Disease (n=280)Position in Model Variable P ValueFirst Low-Density Lipoprotein Cholesterol <0.0001Second High-Density Lipoprotein Cholesterol 0.0001Third* Hemoglobin A1c 0.0022Fourth* Systolic Blood Pressure 0.0065Fifth Smoking 0.056*Adjusted for age and sex.Turner RC et al. BMJ 1998;316:823-828.
Intensive Multiple Risk Factor Management in Patients with Type 2 Diabetes: STENO-2 60Primary Composite Endpoint* (%) N=160; follow-up = 7.8 years 50 Conventional Therapy 40 20% Absolute Risk Reduction 30 20 Aggressive treatment of†: Intensive Therapy† – Microalbuminuria with 10 ACEIs, ARBs, or combination – Hypertension 0 – Hyperglycemia 0 12 24 36 48 60 72 84 96 – Dyslipidemia – Secondary prevention Months of Follow-up of CVD Primary composite endpoint: conventional therapy (44%) and intensive therapy (24%). *Death from CV causes, nonfatal MI, CABG, PCI, nonfatal stroke, amputation, or surgery for peripheral atherosclerotic artery disease. †Behavior modification and pharmacologic therapy. Slide Source: Adapted from Gaede P et al. N Eng J Med 2003;348:383–393. Lipids Online Slide Library www.lipidsonline.org
99Components of Secondary Prevention • Cigarette smoking cessation • Blood pressure control • Lipid management to goal • Physical activity • Weight management to goal • Diabetes management to goal • Antiplatelet agents / anticoagulants • Renin angiotensin aldosterone system blockers • Beta blockers • Influenza vaccinationSmith SC Jr et al. Circulation 2006;113:2363–2372.