Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) ‘The thd ATP report updates the existing recommendations for cnial management of high blood cholesterol. The NCEP periodically produces ATP clinical updates as warranted by advances in the scence of cholesterol management, Each ofthe gudeline reports—ATP I [land IlI—has a major ‘thrust. ATP [ outlined a strategy for primary prevention of coronary heart dlsease (CHD) in persons with high levels of low density lipoprotein (LDL) ‘cholesterol 160 mgd.) or those with borderine-high LDL cholesterol (130-159 mp) and multiple (2) risk factors. ATP I affred the impor- tance ofthis approach and added a new feature: the intensive management ‘of LDL. cholesterol in persons with established CHD. For CHD patients, ATP Il set anew, lower LDL cholesterol goal of $100 maf. ATP II als call for more intensive LDL lowering therapy in certain groups of people, In accord with recent clinical tral evidence, but its core ts based on ATP and ATP TL, Some of the important features shared with previous reports are shown in Table A in the Append ‘While ATP III maintains attention to intensive treatment of patents with (CHD, its major new feature isa focus on primary prevention in persons ‘with multiple sk factors. Many of these persons have a rearively high risk for CHD and will benefit from more intensive LDL-lowering teatment than recommended in ATP IL. Table 1 shows the new features of ATP I Table 1. New Features of ATP Focus on Miltiplo Risk Factors "x Rosse persons with betes without CHD, most of when py mutipe Tk factors, to te sk level of CHD ree exalt. 1 Uses framnghom proectons of Doar absolte CHD rk (the pexcont Frobatity of having 2 CHD event n 10 yoors) to cent certain pavers tts rutile (2) rex factors for more mene testers, 1 loorutes porsons win muttpto metabotl nsx factors (metabove sro) ts candidates for ntonsiied terapeuai exe changes Modifications of Lipid and Lipoprotein Clasitication (denties {DL cholestrol «100 mg. es ope. 1 Raaes categoreal low HDL cholesterol fem <5 mg to <40 maid. because the later fa beter messi of 2 cepressed HOI. = Suan ghar cnet epi ge ote tran to Support for implementation = Recommends a complete lpoprotin profte otal cholesterol, LDL hotest, HDL cholesterol, a wives) as the profred al t 1 Encourages use of pont senators and vecous (ub) Mt 36 terete dtary options to enhance lowering f LDL ehotesterl 1 Present trata for promoting sdherence to therapaute Meso changes ana aug terepes 1» Recommends testmene beychd LDL owerng for persons with tyes LDL Cholesterol: The Primary Target of Therapy Research from experimental animals, laboratory investigation, epidemiology. and genetic forms of hyperchokesteolemia indicate that elevated LDL choles- terol isa major cause of CHD. Risk Assessment: First Step in Risk Management A basic principles to assess a person's risk status. Risk assessment requires measurement of LDL. cholesterol as part of lipoprotein analysis and identification of accompanying risk determinants. I ftotal cholesterol 2200 mg/d or HDL is <40 mgld, a followun tinonrein nroile & needed for anneonriate ‘management based on LDL.ATP Ill adopts the clasifiation of LDL cholesterol levels shown in Table 2, which also shows the classification of total and HDL cholesterol levels. Tablo 2. ATP Il Classification of LDL, Total, and HDL Cholesterol (mg/dl) LDL Cholesterol <100 Optima 100-128 Near optima¥atove optimal 120-159 Boxderline high 160-189 High 2190 Very high Total Cholesterol <200 Desirable 200-230 Borderline high 2240 High HDL Cholesterol <4. Low 260 High Risk determinants in addition to LDL- cholestrol include the presence or absence of CHD, other clinical forms ofatherosclerotte disease, and the major risk factors other than LDIL (ee Table 3) Table 4 defines categorles and shows coresponding LDL-cholesterol goal. Table 3. Major Risk Factors (Exclusive of LDL Cholostorot) That Modify LDL Goals” = Cgaretto smoking f= Hypertension (BP 2140/00 mnig or n antihypertensive medication) f= Low HDL chotesterat (<40 mg/l) 1 Family history of premature CHD (CHD in male fst degree relative <5 {years CHD in female ist degre relative 20%%. Persons with CHD or CHD risk equivalents have the lowest LDL cholesterol goa! (<100 md). The second category consists of persons with multiple (2+) risk factors in ‘whom 10-year risk for CHD is <20%%, The LDL cholesterol goal for persons vith muliple (2 tsk factors is <130 maid. ‘The thi category consists of persons having 0-1 risk factor; with few exceptions, persons in this category have a 10-year risk <10%. Their LDL, cholesterol goal is <160 mall. ‘Method of tsk assessment: counting major risk factors and estimating 10-year CHD riskFirst, the number of risk factors is counted (Table 3), Second, for persons ‘with multiple (24) risk factors, 10-year risk assessment fs carried out with Framingham scoring to identity individuals whose short-term risk warrants consideration of intensive treatment. isk factors west in Framingham scoring include age, total cholesterol, HDL. cholesterol, blood pressure, and cigarette smoking. Framingham scoring divides persons with multiple rsk factors into those with 10-year risk for CHD of >20%, 10-20%, and <10% Role of other risk factors in risk assessment ATP Ill recognizes that risk for CHD is influenced by other factors Among these are obesity, physical Inactivity, and atherogenic det; Metabolic syndrome Many persons have a constellation of major risk factors, life-habit risk factors, and emerging risk factors that constitute a condition called the _metabolie syndrome. Factors characteristic of the metabolic syndrome are ‘abdominal obesity, atherogente dyslipidemia. raised blood pressure, Insulin resistance, and prothrombotic and proinflammatory states, ATP I recognizes the metabolic syndrome as a secondary target of risk-reduction therapy, afer the primary target—LDI. cholesterol, The link between risk assessment and cost effectiveness In ATP Ill, a primary aim isto match intensity of LDL lowering therapy ‘with absolute risk. Everyone with elevated LDL cholesterol is treated with lifestyle changes that are effective in lowering LDL levels, Persons at relatively high risk are also candidates for drug treatment, Primary Prevention With LDL-Lowering Therapy The clinical approach to. primary prevention is founded on the public health approach that calls for lifestyle changes, including: 1) reduced intakes of saturated fat and cholesterol, 2) increased physical activity, 3) weight control [LDL goals in primary provention depend on a person's absolute risk for CHD Therapeutic lifestyle changes are the foundation of clinical primary prevention. some persons at higher tisk are candidates for LDL-lowering drugs ‘Ary person with eewated LDL cholesterol or other form of hyperiigeia should Undergo cial or laboratory assesment to ule out secondary dysipiema before inition of ipitdowering therapy. Causes of secondary dsipidema include: + Dianetes + Hypatnyorsien + Otsiructive er seas + Chron ena fare + Drugs nat cease LDL crolestero and dosrease HDL cholesterol (progestins, anabote seria, and catia (re scr esa aw acho appropiate pny senna bests ek oy fe eee ‘Secondary Prevention With LDL-Lowering Therapy LDL-owering therapy reduces total mortality, coronary mortality, major coronary evens, coronary artery procedures, and stroke in persons with established CHD. LDL cholesterol lovel of <100 mgd. s optimal NTP specifies an LDL cholesterol <100 mgd asthe goal of therapy in secondary prevention, When persons are hospitalized for acute coronary syndromes lipid measures should be taken within 24 hours. ‘These values can guide the physieian on initiation of therapy ‘Adjustment of therapy may be needed afer 12 weeks. LDL-Lowerina Therapy in Three Risk Cateaories ‘The two major modalities of LDL-lowering therapy are therapeutic lifestyle ‘changes (TLC) andl drug therapy. ‘Table 5 dines LDL cholesterol_goals and cutpoints for intition of TLC and for drug consideration for persons with three catezories of isk Table §: LDL Cholesterol Goals and Cutpoints for Therapeutic Lifestyle Changes (TLC) and Drug Therapy in Different Risk Categories, ok Category LDL Goal LOL Level Deter Stach to tate ak Wiech to ‘rerapeute teste Consier Dru Ghanges tio) Therapy CHD or CHD Rsk <100malst 2100 male 3120 wal Feqnotets {100-128 ml: (voy i 20%) rg optional ‘o,ear ik 102096: 2+ RikFacios — <130mglet 2120 moth S130 mg (roar i 209) “Ooo nk TORE S160 moi 0-1 sk Facts! <160mgldl_ 2160 maith. 2100 mal {160-180 mi: [oLoweeng rug crsionat| (CHD and CHD sk equivalents ‘Te cut-points for initiating lifestyle and. drug therapkes are shown in Table 5 «= If baseline LDL cholesterol is 2130 mgidL, intensive lifestyle therapy and maximal control of other risk factors should be started. Moreover, for most patients, an LDL-lowering drug wil be required to achieve an LDL. cholesterol <100 mL; thus an LDL cholesterol lowering drug can be started simultaneously with TLC to attain the goal of therapy. ‘+ IFLDL cholesterol levels are 100-129 mg/l ether at baseline oF on LDL-towering therapy, several therapeutic approaches are available: + Initiate or intensify lifestyle andlor drug therapies specifically to lower LDL. + Emphasize weight reduction and increased physical activity in persons ‘with the metabolic syndrome, + Delay use or intensification of LDL-lowering therapies and institute ‘treatment of other lipid or nonlipi risk factors: consider use of other lipid-modifying drugs i the patient has elevated triglyceride or low HDL cholesterol. 1 If baseline LDL cholesterol is <100 mg/dL, Further LDL -lowering therapy is not required. Multiple (2+) risk factors and 10-year risk <20% = Multiple 2+) risk factors and a 10-year risk of 10-20%. In this category. the goal for LDL cholesterol is <130 mga, If baseline LDI. cholesterol is 130 mafaL, TLC is initiated and maintained for 3 months. If LDL. remains 2130 mg/d. after 3 months of TLC, consideration can be given to starting ‘an LDL-lowering drug 1» Matipe (+) risk factors and a 10-year risk of <10%. In this category the goal for LD. cholesterol also is <130 mg/dL. IF baseline LDE cholesterol is 2130 mg/dL, the TLC Diet ts initiated to reduce LDL cholesterol. IF LDL is <160 mg/dl. on TLC alone, it should bbe continued. LDL-lowering drugs generally are not recommended! ‘because the pationt is not at high short-trm risk. LDL cholesterol is 2160 mg/l, drug therapy can be considered to achieve an LDL cholesterol <130 maid; the primary aim isto reduce ong,term risk. Zero to one risk factor Most persons with 0-1 risk factor have a 10-year risk <10%%, The goal for LDL cholesterol inthis risk category i <160 mg/L. First-line therapy is TLC. LDL cholesterol is 160-189 mgldL after an adequate trial of TLC, «drug therapy is optional Factors favoring use of drugs include:fs Asovere single risk factor (heavy cigarette stoking, potly controlled Figure 3A Model of Steps in Therapeutic iexye Changes 10) hypertension, strong family history of premature CHD, or very low HDL. cholesterl); = Maatipl life-habit risk factors and emerging risk factors (if measured); 1 10-year risk approaching 10% (if measured; see Appendix) IFLDL cholesterol is 2190 mg/l. despite TLC, drug therapy should be considered to achieve the LDI. goal of <160 mg/dl. ‘Therapeutic Lifestyle Changes in LDL-Lowering Therapy ATP Tl recommends therapeutic lifestyle changes (TLC). Is essential features are: 1 Reduced intakes of saturated fats (<7% of total calories) and cholesterol (200 mg per day) (ee Table 6 for overall compesition of the TLC Diet) 1» Therapeutic options for enhancing LDL lowering such as plant stanolssteros 2 gay) and increased viscous (soluble) fiber (10-25 glday) 1 Weight eduction 1 Tncreased physical activity 1 Table 6. Nutrient Composition of the TLC Diet seanutaiye |" Jvteie [| eve to. enter seamen fee ofet e LDL goat not FDL goat nat me ei) |S eam] [Strat Loge ena She Ee gate cos Se ae eel, | toe ees ae |, Sea Ss en |oresrma sunt Sie | ey Drug Therapy to Achieve LDL Cholesterol Goals When drugs are prescribed, attention to TLC should always be maintained and reinforced Je 7 Drags Affecting Lipoprotein Metabalam Drug dss, Agents Upidiipoprotein Side Efects Convaindeations Cael Taal, Natriont Recommended Intake snd bay bose eae oie Saturated ft” Less than 79 of total calories WMG CoRreavcaso UL B56 Myopatiy, Abo: Reds man nbtor aun HDL TS5%. ewe er Ato cron Sam Polyunsaturated at Up to 10% of ttl aleries restoains 1 Tego ayn” gate” es CHD Monounsatusted ft Up 1.20% of oa calories Bae See rt Total fat 25-35% of total calories use of certain Prosedurs: Carbohydrate! 50-60% of total calories ee {total moralny Fiber 20-30 g/day Proin Aeprorimatly 15% of otal calories aye oy ysso% ganna suse Reuse ‘Cholesterol Less than 200 ma/day ‘Sequestrants! ‘HOL = 13.5% distress * dysbeta- ae Total calves (enero aac energy ake and expenditure to Te fo Gomain "ipetroma, a ‘maintain desrable body weight/prvent se” Sepia ot past ‘weight gain other drugs 1 5200 mo Nevtricocit UL L5.25% Fting Anoka: Rata mar He isos Hypa “Chenery A model of steps in TLC is shown in Figure 1. To initiate TLC, intakes of To OSI pear ok Pom (gon) Sete ort sotuated fats and cholesterol ae reduced fist to lower LDI cholesterol Upoe st it Ieee ctype One exception is that total fat is allowed to range from 25-35% of total SeeONENY Spee iar 4s ‘ee calories provided saturated fats and trans flty acids are kept low. A higher "eae (irish, Cates "Sonam Eamon moron Ywepary dea intake of total fat, most in the form of unsaturated fat, can help to reduce FOC" 02% (Peg °c trigherides and raise HDL cholesterol in persons with the metabolic ae Woy syndrome, In accordance with the Dietary Guidelines, moderate physical activity is encouraged. After 6 weeks, the LDL response is determined: ‘Mtr maximum reduction of LDL cholesterol with dietary therapy, enphasis shifts to management of the metabolic drome and associated lipid risk factors. Secondary prevention: drug therapy for CHD and CHD risk equivalents For persons with CHD and CHD risk equivalents the goa sto attain an LDL cholesterol! level <100 mgi.. Most CHD patients will need LDL- lowering drug therapy. Other lipid risk factors may also warrant considera tion of drug treatmentLD Lowering drug therapy for primary prevention ‘The general approach to management of drug therapy for primary prevention is outlined in Figure 2. Fur 2, oreo Drug Tay in Pinay Preven Tate ibcgeanet | [Loge Monier LoLoweing | | teensy) adhe erst response and augthepy |x Lowery |S | ugtierapyor | 985 | theres to Ls|trapy Lp fertoateis > teay ‘pet sSuvusina a Camitsiger a rg bie aid dovatsainor "ane eat eget aiibaed axe vote sequstartar fatus wi When crug therapy fr primary prevention ia consideration, the third vist of etary therapy (see Figure 1) wil typically be the visit to initiate drug treatment. Even if drug treatment is started, TLC should be continued. As with TLC, the fist priority of drug therapy ito achieve the goal for LDL cholesterol. For this eason, an LDL lowering cru shouldbe started. ‘After 12 weeks of drug therapy, the respons to therapy should again be assessed. If the LDL cholesterol goal is till not achioved, consideration can be given to further intensification of drug therapy. I the LDL goal cannot be attained by standard lipid Jowering therapy, consideration should be given to seeking consultation from a lipid specialist. Benefit Beyond LDL Lowering: The Metabolic Syndrome as a Secondary Target of Therapy Evidence is accumulating that risk for CHD can be reduce beyond, LDL-lowering therapy by modification of other risk factors. One potential secondary target of therapy isthe metabolic syndromes. This syndrome is closely linked to a generalized metabolic disorder called insulin resistance The risk factors ofthe metabolic syndrome are highly concordant; in aggregate they enhance risk for CHD at any given LDL cholesterol level For purposes of ATP Il, the diagnosis of the metabolic syndrome is made ‘when three or more ofthe risk determinants shown in Table 8 are present ‘These determinants include a combination of categorical and borderline risk factors that can be readily measured in clinical practice, Table 8. Clinical Identification of the Metabolic Syndrome Risk Factor Defining Level ‘Abdominal Obesty* Waist Circumference! Men >102 cm (40 in) Women 88 cm (535 in) Triglycerides 2150 mgial HDL cholesterol Men -<40 mgfa Women -<50 mgfal. Blood pressure 2130285 mmHg Fasting glucose 2110 mglal Management of the metabolic syndrome has a two-fold objective: (1) to reduce underlying causes (Le., obesity and physical inactivity), andl (2) to treat assocated nonlipld and lipid risk factors Management of underlying causes of the metabolic syndrome Weight contol. Physical activity.