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NCEP ATP III: 2004 Updated LDL-C Goals, Treatment Cutpoints

Risk CategoryLDL-C GoalInitiate TLCConsider Drug TherapyLower risk: 01 risk factor

ATP II : () LDL- < 100 mg/dl.

10- > 20% : . ( 126 mg/dl)

. . . . ATP IIINCEP : ATP III JAMA 2001;285:2486-97.

MRFIT: Stamler J et al. Diabetes Care 1993;16:434-444. No DiabetesDiabetes01236311259229147125TC > 200 mg/dL SBP > 120 mm Hg Current smoker

7- Haffner SM et al. N Engl J Med 1998;339:229-234. (%)

18.83.545.020.2P

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Slide SourceLipidsOnlinewww.lipidsonline.org

NCEP ATP III: The Metabolic Syndrome (2001)Diagnosis is established when 3 of these risk factors are presentExpert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA 2001;285:2486-2497.

Risk FactorDefining LevelAbdominal obesity (Waist circumference)MenWomen>102 cm (>40 in)> 88 cm (>35 in)TG150 mg/dlHDL-CMenWomen

Prevalence of the NCEP Metabolic Syndrome: NHANES III by Age4049Ford ES et al. JAMA 2002;287:356-359.Prevalence %2070+Age, years202930395059606970MenWomen24%23%8%6%44% 44%

-N=4.156 Athyros et al. Diabetes Obesity and Metaboliosm 2005;7:397-405.

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Men244.9111930434325.1538.6666666667

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Cardiovascular Disease Mortality Increased in the Metabolic Syndrome: Kuopio Ischaemic Heart Disease Risk Factor StudyLakka HM et al. JAMA 2002;288:2709-2716.Cumulative Hazard, %026812Follow-up, yearsYESMetabolic Syndrome:NOCardiovascular Disease Mortality RR 3.55 (+355%)410

355 % .Lakka HM et al. JAMA 2002;288:2709-2716.

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N .. The Atypical Antipsychotic Therapy and Metabolic Issues National Survey Practice Patterns and Knowledge of Psychiatrists. J Clin Psychopharmacol 2004;24:S1S6

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Atypical Antipsychotics and Metabolic Abnormalities Risk for WorseningNasrallah , Newcomer JW. J Clin Psychopharmacol 2004;24:S7S14

Agent Weight Gain Diabetes Lipid Profile Clozapine +++ + + Olanzapine +++ + + Risperidone ++ Data Data Quetiapine ++ Data Data Aripiprazole* +/- - -Ziprasidone* +/- --

+ indicates increased effect - no effect.

O

CATIEClinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Investigators

Effectiveness of Antipsychotic Drugs in Patients with Chronic Schizophrenia

Lieberman JA, et al N Engl J Med 2005;353:1209-23.

> 7%Lieberman JA, et al. N Engl J Med. 2005;353:1209-1223. (%)N=185N=341N=337N=336N=261

Lieberman JA, et al. N Engl J Med. 2005;353:1209-1223 (mg/dL)N=143N=262N=268N=286N=212

Lieberman JA, et al. N Engl J Med. 2005;353:1209-1223 (mg/dL)N=143N=262N=268N=286N=212

QTc Lieberman JA, et al. N Engl J Med. 2005;353:1209-1223Mean change from baseline (msec)N=185N=341N=337N=336N=261

CATIE :

,

Lieberman JA, et al. N Engl J Med. 2005;353:1209-1223

Comparative study of the development of diabetes mellitus in patients taking risperidone and olanzapine Fuller MA, et al. Pharmacotherapy. 2003 Aug;23(8):1037-43 .

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Baptista T, et al. Pharmacopsychiatry 2002;35:205-19. Obesity and related metabolic abnormalities during antipsychotic drug administration: mechanisms, management and research perspectives.

.

Baptista T, et al. Pharmacopsychiatry 2002;35:205-19. .

, , .

Obesity and related metabolic abnormalities during antipsychotic drug administration: mechanisms, management and research perspectives.

Melkersson KI, et al. J Clin Psychiatry 2000;61:742-9. Elevated levels of insulin, leptin, and blood lipids in olanzapine-treated patients with schizophrenia or related psychoses , , , . .

Weiden et al. J Clin Psychopharmacol 2003;23:595-600.P

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TOY OPOYWeiden et al. J Clin Psychopharmacol 2003;23:595-600.P

Disparities in care drive excess CVD mortality in severe mental illness Data on 88,000 patients hospitalized for MI show mortality increases during the follow-up period of 19% in persons with any mental disorder and 34% in those with schizophrenia, with increases in mortality related to reductions in the quality of care.

1500 patients with chronically treated schizophrenia data conducted at 57 US sites found that 88% of patients with dyslipidemia, 30% with diabetes, and 62% with hypertension were not receiving appropriate pharmacotherapy for these conditions. Newcomer JW, Hennekens CH. JAMA 2007 (7 Nov); 298: 1794-1796 .

Disparities in care drive excess CVD mortality in severe mental illness Although some antipsychotic drugs can adversely affect adiposity as well as glucose and lipid metabolism, screening for hyperglycemia and dyslipidemia occurs at very low rates in patients with severe mental illnesses, including those who are treated with antipsychotic medications.

Low rates of dyslipidemia and glucose screening are likely to contribute to underdiagnosis and undertreatment for modifiable CVD risk factors in this population, including the effects of medications used for treatment.

Newcomer JW, Hennekens CH. JAMA 2007 (7 Nov); 298: 1794-1796 .

Disparities in care drive excess CVD mortality in severe mental illness Persons with severe mental illness lose 15- 25 years of life chiefly due to CVD and consistently substandard care.

Drawing attention to disparities in prevention and treatment efforts for CVD in patients with mental illnesses.Newcomer JW, Hennekens CH. JAMA 2007 (7 Nov); 298: 1794-1796 .

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CG: ATP III1.75AMRFIT: diabetes amplifies risk from other risk factorsThe Multiple Risk Factor Intervention Trial (MRFIT) considered the effect of diabetes with and without other risk factors (elevated total cholesterol, elevated systolic blood pressure, and current smoking) on cardiovascular disease death rates in 380,000 subjects. Cardiovascular risk factors predicted cardiovascular disease death rates both in subjects with diabetes and in subjects without diabetes. In this study, the presence of diabetes was equivalent to the presence of 23 risk factors.

Reference:Stamler J, Vaccaro O, Neaton JD, Wentworth D. Diabetes, other risk factors, and 12-yr cardiovascular mortality for men screened in the Multiple Risk Factor Intervention Trial. Diabetes Care 1993;16:434-444.Incidence of MI during a 7-year follow-up in a Finnish populationIn a population-based study conducted in eastern and western Finland, more than 1,000 diabetic subjects and almost 1,400 nondiabetic subjects were followed up for 7 years. Subjects were stratified by baseline status for both prior MI and diabetes. Subjects who had both a prior MI and diabetes had a higher risk of a future MI. Subjects with diabetes but without a prior MI had a similar risk of future MI as nondiabetic subjects with a prior MI. This study thus supports the concept of diabetes as a CHD risk equivalent.

Reference:Haffner SM, Lehto S, Ronnemaa T, Pyorala K, Laakso M. Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Engl J Med 1998;339:229-234.

ATP III: the metabolic syndromeThe NCEP ATP III guidelines define 5 components of the metabolic syndrome; at least 3 of the 5 criteria are required for the diagnosis of the metabolic syndrome. Note that the NCEP metabolic syndrome has different criteria for triglycerides and HDL-C, unlike the WHO definition, which lists high triglycerides and/or low HDL-C as a single factor. Almost all individuals in North America who have the metabolic syndrome have a high waist circumference as one of the criteria. Note also that the NCEP definition of the metabolic syn