AUTHOR DISCLOSURE INFORMATION

1. Isolated Non-specific ST-segment and T-wave Abnormalities in a Cross Sectional US Population and Mortality - Insights from NHANES III ApurvaO. Badheka, MD; AnkitRathod, MD; George R. Marzouka, MD; Nileshkumar Patel, MD; SyedS. I. Bokhari, MD; Mauro Moscucci, MD; Mauricio G. Cohen, MD SPEAKER: Apurva Badheka MENTOR: Mauricio Cohen AUTHOR DISCLOSURE INFORMATION This presentation is the original work of the authors listed above. There are no grants, contracts, or other forms of financial support to disclose. None of the authors have any relationships with industry to disclose.

2. BACKGROUND: • Major ST-segment and T-Wave changes are an important predictor for coronary heart disease (CAD) and cardiovascular mortality. • Minor or non-specific ST-segment and T-wave (NS-STT) abnormalities are regarded by clinicians to be incidental, transient and often benign findings in asymptomatic individuals. • However NS-STT abnormalities may be signs of hypertension and early CAD. • Few studies have explored the prognostic value of NS-STT in a nationally cross-sectional population free of CAD for CVM.

3. OUR STUDY : • Study design : Retrospective cohort study using NHANES III data set (1988-1994) • Study sample : 4437 adults between 40-90 years without known CAD / equivalents with available ECG data • Follow up period: Mean of 13.51 years/patient. Total follow up period of 59,953.83 patient years. • Primary clinical outcomes: Cardiovascular mortality and all cause mortality • Mortality: From National Death Index Certificate records upto Dec 31, 2006 • ECG analysis: Minnesota coding

4. SOME DEFINITIONS : • Major ECG abnormalities : MC 1.1/1.2, 4.1/4.2, 5.1/5.2, 6.1/6.4/6.8, 7.1/7.2/7.4, 8.3, 9.2 • Possible LVH by ECG: MC 3.1, 3.3 • Evidence of MI on ECG: Myocardial infarction/injury score ≥ 20 • Cardiovascular disease death: ICD-10 coding, I00-I99 • eGFR: per MDRD formula • Hypercholesterolemia: By self reported history, medication use or LDL level. Goal LDL per ATP III criteria.LDL (mg/dL)=Total cholesterol-HDL-0.20*Serum triglycerides • Hypertension: By self reported history, medication use or BP >=140/90 • Diabetes: By self reported history, medication use or HbA1C>=6.5 • QTc: Per Bazett’s formula • Normalized Calcium: Ionized calcium level adjusted for pH.

5. Non-specific ST-segment and T-wave abnormalities • MC 4-3: No ST-J depression >0.5mm, but ST-segment downward sloping and ST-segment or T-wave nadir at least 0.5 mm below P-R baseline, in any of leads I, II, aVL, or V2 to V6 • MC 4-4: ST-J depression of >1mm and ST-segment upward sloping or U-shaped, in any of leads I, II, aVL, or V1 to V6 • MC 5-3: T-wave amplitude zero (flat), negative, or diphasic (negative-positive type only) with negative phase < 1mm in lead I, II, V3 to V6, or in lead aVL when R-wave amplitude >5mm • MC 5-4: T-wave amplitude positive and T- to R-wave amplitude ratio <1:20 in any of leads I, II, aVL, or V3 to V6 when R-wave amplitude in the corresponding leads >10mm

6. STUDY SAMPLE: Number Of Participants With ECG data = 8561 • 1550 participants with major ECG abnormalities • 7 with HR>120 bpm, 559 with possible LVH • 324 with evidence of MI on ECG • 170 with rhythm other than sinus • 91 non-responsive were excluded 5860 • 1 participant with missing f/u data • 223 with PMH of MI • 285 with h/o chest pain s/o angina • 84 with CHF, 126 with Stroke • 684 with DM (h/o, medicine or HbA1C>=6.5) • 20 with PAD were further excluded Final Study Sample 4437

7. STATISTICAL ANALYSIS: • NHANES III had a complex nonrandom multistage stratified sample design • All analyses were performed using designated weighting specified in datasets representing a similar US population of 48,639,307 persons • Differences in baseline characteristics between categories were examined by simple linear regression for continuous variables and chi-square for categorical variables • Kaplan-Meier curves were used for univariate analysis of cardiovascular and all-cause mortality • Cox proportional hazard regression model was used to calculate the hazard ratio (HR, 95% confidence interval, p-value) of cardiovascular mortality and all-cause mortality for possible predictors.

8. BASELINE CHARACTERISTICS:

9. BASELINE CHARACTERISTICS

10. CARDIOVASCULAR MORTALITY :

11. ALL CAUSE MORTALITY :

12. Cardiovascular Mortality In Subjects With And Without NS-STT Changes.

13. All-cause Mortality in Subjects With And Without NS-STT Changes

14. Strengths and Limitations: • One of the largest study of its kind • “Clean” sample of asymptomatic patients • Most prior studies have focused disproportionately on middle aged white men • Weighted analysis of a large cross sectional representation of US population • Strict definitions of hypercholesterolemia, hypertension and diabetes • Mortality risk of NSSTT shown to be similar to that of traditional risk factors • Limited by lack of follow up ECG (?transient) • Machine coded, not manually verified

15. Conclusions: • Present USPTF guidelines recommend against routine screening ECGs • Given that ECGs are relatively inexpensive, accessible in most outpatient clinics, and can offer a wealth of information on cardiovascular health, it may be prudent to add ECG testing to our cardiovascular risk assessment. • Minor NS-STT abnormalities may help discriminate patients at higher risk for mortality and perhaps benefit from more aggressive risk factor modification.