Isolated Non-specific ST-segment and Isolated Non-specific ST-segment and T-wave Abnormalities in a Cross T-wave Abnormalities in a Cross

Sectional US Population and Mortality Sectional US Population and Mortality - Insights from NHANES III- Insights from NHANES III

Apurva O. Badheka, MD; Ankit Rathod, MD; George R. Marzouka, MD; Nileshkumar Apurva O. Badheka, MD; Ankit Rathod, MD; George R. Marzouka, MD; Nileshkumar Patel, MD; Syed S. I. Bokhari, MD; Mauro Moscucci, MD; Mauricio G. Cohen, MDPatel, MD; Syed S. I. Bokhari, MD; Mauro Moscucci, MD; Mauricio G. Cohen, MD

AUTHOR DISCLOSURE INFORMATIONAUTHOR DISCLOSURE INFORMATIONThis 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.

SPEAKER: Apurva Badheka MENTOR: Mauricio Cohen

BACKGROUND: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.

OUR STUDY :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

SOME DEFINITIONS :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.

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

Non-specific ST-segment and T-wave abnormalities

STUDY SAMPLE:STUDY SAMPLE:

STATISTICAL STATISTICAL ANALYSIS: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.

BASELINE CHARACTERISTICS:

a Hypertension was defined as either self reported history of high blood pressure/hypertension or participants are taking medication for high blood pressure or during physical examination participants have systolic blood pressure>=140 mmHg and or diastolic blood pressure >= 90 mmHg. b History of hypercholesterolemia was defined as either participants self reported history of hypercholesterolemia or taking medication or low density lipoprotein (LDL) is not in the range of target goal according to ATP3 guidelines. LDL was calculated using the following formula. LDL (mg/dL) =Total cholesterol-HDL-0.20*Serum triglycerides.

Variable NS-STT absent (n=4023)

NS-STT present (n=414)

P-value

Age (years) 56.68 ± 12.91 62.39 ± 12.39 <0.01

Male gender (%) 44.51 32.20 0.0004

Black race (%) 6.75 8.48 0.08

Body mass index (Kg/m2) 27.04 ± 5.12 27.89 ± 5.26 0.039

Hypertension (%) a 33.33 58.36 <0.01

Current smoker (%) 22.13 20.40 0.54

Family history of MI before age of 50 (%)

9.81 12.6 0.23

History of hypercholesterolemia (%) b

50.78 44.94 0.16

BASELINE CHARACTERISTICS

c LDL was calculated using the following formula. LDL (mg/dL) =Total cholesterol-HDL-0.20*Serum triglycerides d GFR denotes glomerular filtration rate. MDRD formula was used to calculate GFR. GFR=186* Serum creatinine -1.154* age-

e, f potassium and normalized calcium is in mmol/L. Normalized calcium value derived from adjusting the measured ionized calcium for pH (Laboratory Procedures Used for NHANES III) (U.S. DHHS, 1996) g QTc interval denotes corrected Qt interval, which was derived using Bazzett formula QTc= QT/√RR. QT= qt interval and RR= rr interval. All intervals are in milliseconds. h LVMI= Left ventricular mass index.

Variable NS-STT absent (n=4023)

NS-STT present (n=414)

P-value

Serum cholesterol 215.92 ± 42.40 222.85 ± 43.47 0.002 Serum triglycerides 146.40 ± 99.88 157.63 ± 100.02 0.02 Calculated LDL c 135.60 ± 38.28 140.14 ± 38.01 0.06 High density lipoprotein 52.20 ± 16.10 51.72 ± 17.39 0.845 GFR d 66.14 ± 19.86 62.05 ± 20.15 <0.01 Potassium e 4.07 ± 0.32 4.02 ± 0.38 0.001 Normalized Calcium f 1.23 ± 0.05 1.24 ± 0.05 0.79 Heart rate 67.89 ± 10.75 68.63 ± 11.36 <0.01 QTc interval (msec) g 427.23 ± 21.89 436.20 ± 26.08 <0.01 QRS duration (msec) 95.53 ± 9.91 96.36 ± 9.61 0.20 PR interval (msec) 161.93 ± 25.96 165.55 ± 28.86 0.23 ECG LVMI g 98.77 ± 17.09 110.81 ± 19.63 <0.01

CARDIOVASCULAR MORTALITY :Variable HR (96% CI) for cardiovascular

death (n=427) P-value

Age 1.13 (1.10-1.15) <0.01

Male 1.43 (1.13-1.81) 0.003

Black 1.28 (0.88-1.85) 0.19

BMI 1.02 (0.98-1.05) 0.28

Hypertension 1.50 (1.04-2.18) 0.03

Smoking 1.97 (1.32-2.92) 0.001

Cholesterol 1.08 (0.82-1.41) 0.59

GFR 0.98 (0.97-1.00) 0.03

Potassium 1.07 (0.70-1.63) 0.75

Heart rate 1.02 (1.00-1.04) 0.05

QTc Interval 1.00 (0.99-1.01) 0.68

LVMI 1.00 (0.99-1.02) 0.43

NSSTT 1.72 (1.03-2.87) 0.04

Here multivariate model was adjusted for age, sex, race, body-mass index, hypertension, h/o cigarettes smoking, hypercholesterolemia, glomerular filtration rate, heart rate, corrected qt interval, left ventricular mass index and non-specific st and t wave changes.

ALL CAUSE MORTALITY :Variable HR (95%CI) for overall

mortality (n=1116) p-value

Age 1.11 (1.10-1.12) <0.01

Male 1.58 (1.38-1.82) <0.01

Black 1.28 (1.04-1.57) 0.02

BMI 1.01 (0.99-1.03) 0.47

Hypertension 1.25 (0.99-1.57) 0.07

Smoking 2.29 (1.87-2.80) <0.01

Cholesterol 1.21 (1.02-1.44) 0.03

GFR 1.00 (0.99-1.00) 0.34

Potassium 1.20 (0.93-1.54) 0.16

Heart rate 1.02 (1.00-1.03) <0.01

QTc Interval 1.00 (0.99-1.01) 0.30

LVMI 1.00 (0.99-1.01) 0.63

NSSTT 1.37 (1.03-1.82) 0.03

Here multivariate model was adjusted for age, sex, race, body-mass index, hypertension, h/o cigarettes smoking, hypercholesterolemia, glomerular filtration rate, heart rate, corrected qt interval, left ventricular mass index and non-specific st and t wave changes

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

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

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

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.