R Dhangana, TP Murphy, MJ Pencina, MB Ristuccia, JV Cerezo, D Tsai Prevalence of Low Ankle-Brachial Index, Elevated Plasma Fibrinogen and CRP Among Those Otherwise at Low- Intermediate Cardiovascular Events’ Risk: Data from the National Health and Nutrition Examination Survey (NHANES)

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Introduction CHD is highly prevalent and responsible for 1 in 5 deaths in US million people suffer coronary attack every year; about 40% die as a result of the attack 2. While primary medical prevention is shown to be very effective, at least 25% of MIs or sudden cardiac deaths occur with little prior warning of cardiovascular disease risk 3. Identifying people for prevention is important 1.Deaths and percentage of total death for the 10 leading causes of death: United States, National Center of Health Statistics. 2.Heart Attack and Angina Statistics. American Heart Association (2003). 3.Myerburg RJ, Kessler KM, Castellanos A. Sudden cardiac death: epidemiology, transient risk, and intervention assessment. Ann Intern Med 1993; 119:

Introduction Risk assessment is usually done using Framingham Risk variables – 75% of adults are low-intermediate risk – But 85% of MI’s/sudden deaths occur in low-intermediate risk Abnormal ABI, elevated plasma fibrinogen and plasma CRP levels have been shown to be associated with increased risk of CHD events and mortality even in those at low- intermediate CHD risk 1-3. However, prevalence estimates of abnormal ABI, fibrinogen and CRP among those not considered at high risk for CHD events have not been reported. 1.Fowkes FG, Murray GD,, et al. JAMA 2008; 300: Danesh J, Lewington S, et al. JAMA 2005; 294: Montecucco F, Mach F. Clin Interv Aging 2008; 3:341-9.

OBJECTIVES To obtain U.S. population prevalence estimates for abnormal ABI, fibrinogen, and/or CRP for individuals without known “CHD-equivalence” with low or intermediate Framingham Risk score having

Definitions “High” Framingham Risk: >=20% 10-year risk of heart attack or coronary sudden death Population without “CHD equivalence”: no history of coronary heart disease or stroke, and without diabetes) Abnormal ABI=ABI <0.9 in either leg Elevated plasma fibrinogen (>=400 mg/dl) Elevated plasma CRP (>3mg/L)

STUDY POPULATION Data from NHANES – NHANES: a large, multicenter survey of the U.S. civilian non-institutionalized population conducted by NCHS of CDC Population sampled to be representative of the overall U.S. population.

INCLUSION CRITERIA Age 40 and older – ABI, fibrinogen, CRP and FRS variables available Participants with hx of diabetes, CHD, stroke or atherosclerotic vascular disease were excluded from further analyses. After all exclusions →→ 6,292 men and women were included.

Interviews & Physical Examinations Histories and Physical Examinations Blood tests and ankle brachial index – Standard ABI methods

STATISTICAL METHODS FRS was calculated based on the use of “Framingham” risk factors tables 1-2 applied to NHANES data. Prevalence estimates (with CIs) were determined for abnormal ABI, fibrinogen and CRP in low-int FRS and high FRS categories. 1. NHANES: Analysis and Reporting Guideline ( 2. Anonymous. ATP III final report. Circulation 2002; 106:

Results Prevalence of ABI =400 mg/dl), and elevated CRP (>3mg/L) in Adults Aged 40 years and older, NHANES ; n = 6292* *No known prevalent history of CHD, Stroke, Diabetes, or Atherosclerotic Vascular Disease % (95% CI) Abnl ABI3.7 (3.3, 4.1) Abnl fibrinogen17.3 (14.7, 19.8) Abnl CRP37.9 (36.0, 39.7)

Framingham Risk Score vs. ABI: n = 5459 Results Normal ABI ≥ 0.9Abnl ABI < 0.9 Low/Int FRS97.0% ( %) 3.0% ( %) High FRS89.5% ( %)10.5% ( %) Framingham Risk Score vs. Fibrinogen : n = 6292 Normal fibrinogenElevated fibrinogen Low/Int FRS83.1% ( %)16.9% ( %) High FRS72.0% ( %)28.0% ( %) P-value <.0001 Normal CRPElevated CRP Low/Int FRS61.3% ( %) 38.7% ( %) High FRS53.9% ( %) 46.1% ( %) Framingham Risk Score vs. CRP: n = 6292 P-value <.0012

Results FRS vs. either abnl ABI or Fibrinogen or CRP : n = 6292 NormalAbnormal/Elevated Low/Int FRS55.3% ( %) 44.7% ( %) High FRS43.8% ( %) 56.2% ( %) P-value <.0001

CONCLUSION Prevalence of abnl ABI, fibrinogen, CRP is high even in those without “high FRS” This is known to correlate with increased events despite “low-intermediate” risk Use in screening could be effective and improve public health