1. Coffee Consumption and Risk of Myocardial Infarction among Older Swedish Women SA Rosner, A Akesson,MJ. Stampfer, A Wolk; AJE; 2007 165:288-293

2. Does coffee consumption increase coronary heart disease (CHD) risk? Case control studies suggested YES Majority of cohort studies suggested NO Most recent cohort studies have shown both increased risk and decreased risk Plausibility of decreased risk: Coffee has anti-oxidant properties and improves insulin sensitivity

3. Study Population Swedish Mammography Cohort established 1987-1990 All women in Uppsala & Vastmanland counties, ages 40-74 were invited to participate in screening Initial 6-page questionnaire (74% response rate) asking about: diet parity age a first birth height and weight educational level follow-up questionnaire (70% response rate) in 1997 diet multi-vitamin/supplement use aspirin use cigarette smoking hormone replacement therapy use history of diabetes, hypertension, and hypercholesterolemia family history of CHD physical activity

4. Study Population Considered as baseline 1997! Smoking status not elicited in 1987 questionnaire and smoking is an important confounder of coffee-CHD association Of the 38,984 women who responded to the 1997 questionnaire, 6,334 were excluded at baseline due to history of MI, ischemic heart disease, stroke, cancer implausible answer to any of the open-ended diet questions implausible caloric intake missing coffee-consumption data or an outcome event during the first month of follow-up

5. Diet and CHD assessment Diet: 96 item, self administered food frequency questionnaire (‘how often on average do you consume…”) Validation with 4 one week diet records: spearman correlations for coffee were 0.61 CHD (fatal and non-fatal) assessed by linkage to Swedish Hospital Discharge Register and Swedish Causes of Death Register (99% completeness in these registers) Diagnostic Criteria according to Swedish National Board of health and Welfare Validation of registry revealed high sensitivity (94%) and a high positive predictive value (86%) for MI compared to other countries

6. Cohort Analyses Person time started accruing Sept 15, 1997 until date of diagnosis of MI, stroke, or cancer (=censored at time of cancer diagnosis) date of death or Dec 31 2002 whichever occurred first Time scale = calendar time for Cox proportional hazard model 4 indicator variables for coffee consumption (0-4 cups/week=referent) {Note: too few non drinkers to compare ever/never} Test for trend using ordinal variable

7. Results Person time 165,896 years (in 32,650 women with coffee consumption data) 459 cases of MI 391 non-fatal 68 fatal Heavy coffee consumers: current smokers HRT use Multivitamin use education

9. Table 1 continued….

10. Crude RR 1 1.05 0.85 0.82 0.87

11. Potential Residual Confounding by Smoking? Restrict to Non-Smokers - 320 cases; 133,014 person-years of follow-up; full covariate adjustment Coffee ConsumptionRR§95% CI§ 0-4 / week1- 5-7 / week0.900.52, 1.56 2-3 / day0.620.37, 1.03 4-5 / day0.580.34, 1.01 >6 / day0.800.42, 1.52 P for trend=0.10

12. Cox Model Stratified by Diabetes Status Non-diabetics, 400 MI cases; 160,472 person-years Coffee ConsumptionRR§95% CI§ 0-4 / week1- 5-7 / week0.710.42, 1.20 2-3 / day0.570.35, 0.91 4-5 / day0.570.35, 0.94 >6 / day0.550.31, 0.98

13. Cox Model Stratified by BMI normal weight BMI=18.5-24-9 kg/m² (225 cases) and BMI >25 kg/m², (210 cases) Normal weightOverweight/Obese Coffee Consumpt ion RR§95% CI§RR§95% CI§ 0-4 / week1-1- 5-7 / week0.880.41, 1.890.680.34, 1.37 2-3 / day0.770.38, 1.560.490.26, 0.94 4-5 / day0.790.38, 1.630.500.25, 0.98 >6 / day0.560.24, 1.340.640.30, 1.37

14. Hypothetical Model Stratified by BMI normal weight BMI=18.5-24-9 kg/m² (225 cases) and BMI >25 kg/m², (210 cases) Normal weightOverweight/Obese Coffee Consumpt ion RR§95% CI§RR§95% CI§ 0-4 / week1-1- 5-7 / week0.980.60, 1.890.750.45, 1.47 2-3 / day1.010.92, 1.250.590.26, 0.90 4-5 / day1.020.85, 1.500.450.25, 0.98 >6 / day1.100.99, 1.340.540.30, 0.98

15. Validity of Exposure Measurement TP=true positive, FP= false positive, FN=false negative, TN=true negative Sensitivity= prop. of subjects truly exposed (or classified as exposed by gold standard) who are identified by test/record as exposed Sensitivity = a / (a+c) Specificity = prop. of subjects truly unexposed (or classified as unexposed by gold standard) who are identified by test/record as unexposed Specificity = d / (b+d) Recorded exposure True exposure (gold standard)Total +- +a (TP)b (FP)a+b -c (FN)d (TN)c+d totala+cb+da+b+c+d

16. Validity of Exposure Measurement Recorded exposure True exposure (gold standard)Total +- +a (TP)b (FP)a+b -c (FN)d (TN)c+d totala+cb+da+b+c+d TP=true positive, FP= false positive, FN=false negative, TN=true negative Predictive Value pos.= prop. of subjects with test/record positive is truely exposed (or classified as exposed by gold standard) PV pos = a / (a+b) Predictive Value neg. = prop. of subjects with test/record negative is truely unexposed (or classified as unexposed by gold standard) PV neg. = d / (c+d)

17. Example: caffeine intake Recorded coffee drinker True coffee drinker (gold standard= urine metabolite levels) Total +- +622284 -7359366 total69 (15%)381 (85%) 450 Sensitivity= 62/69= 90% Specificity= 359/381= 94% Pred value pos= 62/84= 74% Pred value neg= 359/366= 98% Recorded coffee drinker True coffee drinker (gold standard= urine metabolite levels) Total +- +212647 -2401403 total23 (5%) 427 (95%) 450 Sensitivity= 21/23= 91% Specificity= 401/427= 94% Pred value pos= 21/47= 45% Pred value neg= 401/403= 100%

18. Example: MI incidence Recorded MI True MITotal +- +3609369 -216081 total381 (85%)69 (15%) 450 Sensitivity= 360/381= 94% Specificity= 60/69= 87% Pred value pos= 360/369= 98% Pred value neg= 60/81= 74% Recorded MI True MITotal +- +4012403 -262147 total427 (95%) 23 (5%) 450 Sensitivity= 401/427= 94% Specificity= 21/23= 91% Pred value pos= 401/403= 100% Pred value neg= 21/47= 45% Note: predictive values depend strongly on the prevalence of the exposure/ disease (i.e. the numbers in both columns), while sensitivity and specificity do not