Comparison of the Bowling Green Study Risk Factor Graph and the Framingham Risk Score to Predict the Population at Risk of Atherothrombotic Disease

Transcription

1 Comparison of the Bowling Green Study Risk Factor Graph and the Framingham Risk Score to Predict the Population at Risk of Atherothrombotic Disease

2 Introduction Atherothrombotic Disease (ATD) is the leading cause of morbidity and mortality in the western world and in the not too distant future in the entire world. (1) ATD is defined as atherosclerotic disease, with emphasis on the thrombosis that so often precipitates the acute clinical event, such as acute myocardial infarction, acute cerebral infarction, unstable angina pectoris, transient ischmic attacks, abdominal aortic aneurysm, etc. Since not all of a physician s patients will die of ATD, the ability of the physician to protect his/her ATD-prone patient depends directly upon the physician s ability to predict the population at risk of ATD. It is clear that the better one can predict the at-risk population, the better the attending physician can protect his/her at-risk patients from ATD. The Framingham Risk Score (FRS) is the most commonly used risk assessment tool in the USA. (2) Unfortunately, many-perhaps most- American physicians do not calculate FRS values for their patients. (3, 4) The reasons for this failure are probably many, among these reasons may be the time necessary for physicians unfamiliar with the calculations to do those calculations, lack of confidence in the FRS, and disagreement with the scoring process in the FRS. The purpose of this article is to compare the ability of the FRS to predict the population at risk of ATD with the ability of a multifactoral ATD risk factor predictive graph that is termed the Bowling Green Study (BGS) Graph.

3 Materials and Methods The BGS was conceived and initiated by the author in 1974 when he set up his practice of family medicine in Bowling Green, in Northwest Ohio. The population demographic on which this article is based have been described elsewhere (5-7) In brief, however, the BGS study population is not dissimilar to the Framingham population. The BGS study population, like the Wood County population in general, is mainly composed of Anglo Americans, the chief minority being Mexican Americans. African Americans and Asian Americans are present in small numbers. The BGS study population consists of members of both sexes and all age groups. The Bowling Green State University is the largest area employer, with small industries and agriculture offering employment to most of the other BG residents. The details of the development of the BGS Graph have likewise been reported elsewhere. (5-7) In brief, the author entered his private practice of family practice into an age-sex database (the general population data base) beginning in Since the prediction of the population at risk of ATD was less than a precise science in the 1970 s, many of the author s patients sustained ATD events, such that by 1980, the author was able to separate out from the general population database a distinct database for those who had suffered ATD events (the ATD database ). Examination of the ATD database revealed multiple traits that characterized the ATD population. First, the vast majority of younger and middle aged ATD

4 patients were cigarette smokers, the vast majority of middle aged and older ATD patients were past smokers (having quit smoking cigarettes at least six months prior to the presenting ATD event), and the vast majority of older ATD patients were those who had never smoked cigarettes. Overlap between smoking groups occurred, though mainly between past- and never- smokers. Second, most ATD patients had multiple ATD risk factors. The average number of risk factors for men who developed ATD events was 3.5, whereas the corresponding number for women was 2.5. It was therefore obvious that any predictive approach had to utilize multiple risk factors, and as noted above, had to be stratified by cigarette smoking status. Third, the lipid risk factor was not as simple as it might have appeared. High-density Lipoprotein (HDL)- and Low-density Lipoprotein (LDL)-cholesterol determinations were not available to the BGS till all prior lipid testing involved only total cholesterol (CT) and triglycerides (TG). Examination of the ATD data base revealed the usual risk factors of low HDL- and high LDL- levels. However, numbers of ATD patients had normal to high HDL levels or moderate to low LDL levels. In 1981, an article was published entitled Is the LDL:HDL Ratio the Best Lipid Predictor the author regrets that he is unable to supply a better reference since the article has been lost. With the understanding that it was the atherogenic-antiatherogenic balance of LDL- and HDL-cholesterol that was important, the author re-examined the ATD database and found that those ATD patients with high levels of HDL generally had very high levels of LDL whereas those ATD patients with low levels of LDL generally had very low levels

5 of HDL. (In cases where this did not occur, the younger patients were usually cigarette smokers and the older patients were hypertensive, with or without attendant diabetes mellitus.) Initially, the author utilized a simple LDL:HDL ratio. However, in 1983 it occurred to him that what he really wanted to know was how much cholesterol was accumulating within the artery wall. The answer, it seemed, was the difference between the cholesterol entering the artery wall (LDL) and the cholesterol exiting the artery wall by reverse cholesterol transport (HDL), divided by the cholesterol entering the artery wall (LDL). In other words, of the cholesterol entering the artery wall, what percentage remains there. Thus was born the concept of the Cholesterol Retention Fraction, or CRF (defined as [LDL-HDL]/LDL), which is abnormal at levels > In the scenario wherein both LDL- and HDL- cholesterol levels were high, it appeared that HDL-cholesterol was unable to compensate for very high levels of LDL. The level of LDL-cholesterol at which the ability of HDL-cholesterol to compensate for LDL-cholesterol appeared to begin at LDL-cholesterol levels of 170 mg/dl (4.4 mmoles/l). Moreover, the higher the LDL-cholesterol, the less that HDL-cholesterol seemed to be able to compensate, until at LDL-cholesterol levels of 250 mg/dl (6.5 mmoles/l) HDL protectivity was entirely lost. Thus, dyslipidemia worthy of treatment exists when CRF > 0.70 or LDL > 170 mg/dl (4.4 mmoles/l) even if CRF < Fourth, given all of the preceding commentary, the author decided in 1981 to examine combinations of the various ATD risk factors, to determine which

6 combination of ATD risk factors predicted the population at risk of ATD. The author utilized a graphic approach. Only one combination of ATD risk factors accurately predicted the population that developed ATD i.e., a graph with the LDL:HDL ratio (in 1983, converted to CRF) on the ordinate and systolic blood pressure (SBP) on the abscissa. The predictive graph is termed the BGS graph. (See Figure) By 1988 enough patients had developed ATD for the Author to draw an ATD threshold line. The threshold line was not a regression line, but rather a boundary line above which lay the vast majority of CRF-SBP plots of patients who developed ATD, and below which lay the CRF-SBP plots of only a small minority of ATD patients. The threshold line was drawn to enclose the greatest area under the line with the fewest CRF-SBP plots of patients who developed ATD, following the principle of the fewest false negatives. The threshold line was drawn using data, in the main, from patients prior to their developing ATD, and hence could be considered a primary prevention boundary. In 2000, the author published an analysis of eight angiographic regression trials and found one group of patients (L-CAS study) with an average CRF-SBP plot just below the threshold line. (8) Since these regression trials were all done on secondary prevention patients, and since most of the author s patients had never before had their cholesterol levels measured (and hence, the duration of their dyslipidemia could never be known), the author decided to lower the threshold line to compensate for patients who had had their dyslipidemia for a sufficient time to develop atherosclerotic plaques and hence could be considered to have sub-clinical plaque. The new threshold line was presented in the 2000

7 publication. (8) It is this graph, coupled with cigarette smoking status that is compared against the Framingham risk score. The outcomes of the BGS ATD patients are presented in Table I. The favorable advantage of having a CRF-SBP plot lying below (as compared to above) the threshold line, seen in past and never cigarette smokers, is obliterated by current cigarette smokers for this reason, the author feels that cigarette is an independent risk factor for ATD.

8 Results The version of the FRS used in analysis is the 2001 version. (2) A more recent version was published in (9), but on the advise of Peter Wilson, M.D., (personal communication, 30 June 2008) the 2001 version was chosen for analysis because there is no formal adoption of the 2008 approach at this time by the NCEP or any other expert panel group. At the present, I would use ATP3 for risk stratification because that has been accepted by NCEP. The FRS is considered predictive of ATD risk if FRS > 10%; conversely the FRS is not considered predictive if FRS is < 9%. The BGS approach is considered predictive if the CRF-SBP plot is above the threshold line and/or there is any history of cigarette smoking; conversely the BGS approach fails to predict if the CRF-SBP plot is below the threshold line and the patient has never smoked cigarettes (other non-cigarette tobacco use is permitted). On virtually all occasions in which LDL > 170 mg/dl (4.4 mmoles/l) but CRF < 0.69, the CRF-SBP plot lies above the threshold line. The BGS approach is derived from the ATD database of the BGS. Therefore, all patients analyzed have sustained an ATD event, great (acute myocardial infarction, acute cerebral infarction, abdominal aortic aneurysm, etc.) or small (electrocardiogram reveals an old AMI or CAT scan of the brain reveals an old stroke ). This analysis is based on the proposition that the patients are taken at a time prior to their initial ATD event and the comparison is made on the basis of how well the FRS vs the BGS predicted the outcome. This may seem unfair, but both the FRS and BGS are derived from ATD databases, the former in

9 Framingham, Mass, and the latter in Bowling Green, Ohio. Since the Framingham population is not dissimilar to the Bowling Green population, the author feels that the comparisons are valid. This consideration is borne out in Table II, in which the predictive abilities of the FRS and BGS are compared for males. BGS and FRS are in agreement in 85% (287/336) of cases. When the FRS predicts risk, the BGS predicts risk in 285/287 (99%) of patients.there is a discrepancy in prediction in 15% of cases, however. Of the 49 patients with discordant predictions, BGS predicted 47/49 (96%) patients that FRS did not, whereas FRS predicted 2/49 (4%) patients that BGS did not. This same predictive agreement was not seen in women. Table III shows the findings in women. The agreement rate for prediction in women is 40% (99/249). When the FRS predicts risk, the BGS predicts risk in 80/81 (99%) of patients. Of the 150/249 (60%) of cases where BGS and FRS disagree, the BGS predicts 149/150 (99%) of cases not predicted by the FRS, whereas FRS predicts 1/150 (1%) of cases not predicted by BGS. Table IV shows that where FRS > 10%, BGS also precedes risk in men 285/289 (99%) and women 80/81 (99%). The vast majority of cases in which BGS and FRS disagree is in patients in which FRS < 9%. For men, this disagreement affects mainly patients aged < 55 years whereas in women the disagreement extends over the entire age range. In men, where FRS > 20%, 156/157 (99%) of patients will have risk predicted by BGS. Moreover, when FRS =10-19%, 129/130 (99%) will have risk predicted by BGS, and when FRS < 9%,

10 only 47/49 (96%) will have risk predicted by BGS. In women, when FRS > 20%, 18/18 (100%) will have risk predicted by BGS. When FRS =10-19%, 58/63 (92%) of women will have risk predicted by BGS, and when FRS < 9%, 149/168 (89%) will have risk predicted by BGS Table V shows the average age of ATD onset in the various FRS groupings, for men and for women. In men, it will be noted that as the relative risk of ATD increases, so does the average age of ATD onset. Similar findings are noted in women. However, whereas most men have FRS > 10%, most women have FRS < 9%. On the other hand, the highest FRS risk ( > 20%) is seen in the oldest patients, undoubtedly because of points assigned for age. Space does not permit the presentation of more data on this matter in table format; however, most of the FRS scores < 9% are found in men aged 55 years or less (92%) while in women most of FRS score < 9% are found in the < 65 year old group (56%). Conversely, the highest FRS scores (> 20%) are found in men and women aged years old. In other words, people who eventually developed ATD at the youngest ages had the lowest FRS points totals and the lowest predicted relative risk of ATD. All practicing physicians know that ATD events are much more likely to occur in older patients than in younger patients. Table VI reveals risk factor abnormalities at the highest levels in patients whose FRS < 9% and hence would not be treated. 18% of males and 32% of females with FRS < 9% had LDL levels exceeding 170 mg/dl (4.4 mmoles/l). 6% of males and 7% of females had SBP > 180 mmhg; 10% of males and 17% of females had diabetes mellitus. Finally, 14% of males and 12% of females had

11 CRF > The average age of ATD onset for the men and women with these LDL abnormalities were 40 and 62 years respectively. The average ages of ATD onset for men and women with these SBP abnormalities were 42 and 62 years respectively. The average ages of ATD onset for men and women with diabetes were 48 and 65 years respectively. And finally, the average age of ATD onset in men and women with these CRF abnormalities were 44 and 54 years respectively. The final table (Table VII) reveals the CRF-SBP plot position of patients with FRS < 9%, stratified by cigarette smoking status. In general the average ages of ATD onset are the youngest (38 year for men and 56 year for women) for those whose CRF-SBP plot position is above the threshold line and who also smoked cigarettes, and the oldest (53 years for men and 64 years for women) whose CRF-SBP plots are below the threshold line and who never smoked cigarettes. This is the same pattern seen when all FRS patients are considered (Table I).

12 Discussion The BGS and FRS utilize the same basic predictive mechanism: dyslipidemia, hypertension, and cigarette smoking. (In addition the FRS adds points for age.) Since the same general predictive risk factors are used, it is reasonable to compare these two predictive tools, to assess their abilities to predict the population at risk of ATD. The FRS uses its risk factors as independent variables, assigning points for various risk factor abnormalities and totaling up the number of points to assign of relative risk of future ATD. The BGS, on the other hand, uses its lipid and blood pressure predictors as dependant variables, thereby making its prediction (the BGS Graph) a continuous variable. The BGS assigns independent risk factor status to cigarette smoking. Differences in FRS and BGS lie in the use of CT and HDL by the FRS, with each risk factor viewed independently, whereas the BGS uses LDL and HDL as dependant variables. By assigning a certain number of points to each variable, the FRS compromises its predictive abilities because, for example, a CT of 280 mg/dl receives the same number of points as does a CT of 450 mg/dl and likewise a HDL of 39 mg/dl receives the same number of points as a HDL of 20 mg/dl. This means that lipid moieties of vastly different atherogenic/antiatherogenic potential are assigned the same point values. From a dyslipidemia management stand point, then a 26 year old male with CT=280 mg/dl and HDL=39 mg/dl has the same point total (13 points) as a patient with CT=450 mg/dl and HDL=20 mg/dl (13 points) but the risks of ATD are vastly different. (Similar point totals in this case 15 points accrue for a 26-year-old

13 woman.) Moreover, elevated CT can occur due to elevated TG, which may have no atherogenic potential. (10) The assignment of points for age is also a problem. The point score for younger patients is in the negative range and increases into the positive range as patients get older. Indeed, in the population on which this paper is based, the FRS scoring system, by subtracting points for younger patients, takes away sufficient points from the final total to render a score worthy of treatment to a score not worthy of treatment. For example, a 36 year old male patient of mine with a lipid profile of CT=334 mg/dl, HDL=33 mg/dl, LDL=265 mg/dl, and TG=178 mg/dl has a FRS of 9 points (FRS=5% risk) and yet sustained an acute myocardial infarction. He had never smoked cigarettes, did not have hypertension, and was neither diabetic or obese. His CRF was 0.88, which would have placed him in the highest range, demanding immediate treatment; however, he would not have been treated by FRS criteria. A 37-year-old woman, with a lipid profile of CT = 278 mg/dl, HDL = 38 mg/dl, LDL = 187 mg/dl and TG = 265 mg/dl has a FRS score of 19 points and relative risk of 8%, which does not qualify her for treatment. (She did smoke cigarettes, but was not hypertensive, diabetic, or obese) Her CRF was 0.80, putting her in the highest risk category and demanding immediate treatment. She sustained a myocardial infarction. In either case, had points not been subtracted for a younger age, the resultant scores would have placed both patients into FRS categories that would have required treatment. Clearly, the FRS point assignments for younger patients fails to give adequate emphasis on inherited lipid abnormalities and the

14 power of cigarette smoking to induce ATD events. Conversely, since the points allowed for advancing age are greater as the patient gets older, some elderly patients (aged years, for example) have point scores worthy of treatment but made up primarily of points due to age. 89% of men and 58% of women in this age group have at least 75% of their FRS score made up of age points alone. (Data not shown). And age is a nonmodifiable risk factor. FRS gives a high number of points for current smoking in patients aged less than 40 years. It then progressively decreases the number of points for smoking cigarettes over the subsequent decades, as if the longer one smoked cigarettes the less dangerous the cigarette habit is. (That can not be true, as any practicing physician can testify.) Moreover, no points are allowed for a history of smoking as if one could smoke for 40 years, quit, and have a vascular tree as pristine as that of a never smoker. This is untrue. (11) FRS allows the same number of points for a cigarette smoker aged years as for a SBP of mmhg in either sex. Moreover, female patients receive more points for SBP at any level of SBP >120 mmhg than awarded males at the same level of SBP. To the author s knowledge, the are no reports that indicate that hypertension (or even pre-hypertension ) itself has different effects on the male and female vascular system. Additionally, SBP of 160 mmhg gets the same number of points as SBP = 240 mmhg, yet the effect of SBP = 240 mmhg is vastly greater than the effect of SBP of 160 mmhg. Finally, SBP of 240 mmhg is awarded the same number of points as a treated SBP of 130

15 mmhg. BGS, on the other hand, holds that cigarette smoking is an independent risk factor for ATD, and that ATD events can occur in the absence of other ATD risk factors. The evidence for this is borne out in Table I where it is seen that cigarette smokers with CRF-SBP plots below the ATD line have their ATD events, on average, of an earlier age than do non-smoking patients with CRF-SBP plots above the threshold line. Moreover, ATD events in smokers occur earlier than do ATD events in past smokers, who in turn have their ATD events at a slightly earlier age than do never-smokers. (7) Hence, BGS does not diminish cigarette smoking as a risk factor on the basis of length of time smoking and it does give risk factor status to a past history of smoking. Similarly, it is the experience of the author that some people, mainly those with CRF-SBP plots below the threshold line and who are not current cigarette smokers, can achieve advanced years (> 80 years old) with little in the way of clinical ATD. Hence, the BGS does not give major risk factor status to age. It is the observation of the BGS that people with more severe risk factors (CRF, cigarette smoking, and SBP) tend to have ATD events earlier in life, whereas those with milder risk factors tend to have ATD events later in life. (7) Table I demonstrates that ATD events, in patients with CRF-SBP plots below the threshold line and who have never smoked cigarettes, occur so late in life that such patients are virtually immune to ATD. It must not escape comment that the FRS predicts mainly in older patients and fails, often, to predict in younger patients. The author has pointed out

16 various reasons why this occurs namely the negative points awarded younger ages and the diminishing points with age awarded with cigarette smoking and CT, as well as the same number of points awarded for vastly different CT, HDL, and SBP at the high-risk ends of the spectrum. This can not be tolerated in an ATD predictor. The BGS approach avoids this predictive scenario, as it identifies the younger patients at risk of ATD very well. (7) Finally, because points are assigned for the various risk factors and because the points accumulated by a severe abnormality of a single risk factor are submerged in the pool of points awarded for the other risk factors, severe abnormalities of any one risk factor may not accumulate enough points to warrant treatment. Examples of this (from the BGS population) for lipid disorder have already been pointed out, but the same could be said for hypertension. Such a scenario could not occur in the BGS approach, since a severe lipid or hypertensive disorder will virtually always place the CRF-SBP plot above the threshold line and hence render the patients worthy of treatment. Various imaging studies have shown the presence of subclinical atherosclerosis in people, women more so than men, with FRS values that are not worthy of treatment. Karim, etal, used three imaging modalities (carotid intima-medial and thickness onultrasound, and coronary artery/aorta calcification, determined by CAT scan) and found that 69% of patients with FRS < 9% had evidence of subclinical atherosclerosis. (12) Taylor, etal, found that sudden cardiac death in patients with stable plaque, 15/27 (56%) had FRS < 9, whereas those with plaque erosion 18/22 (82%) has FRS < 9%. The reverse

17 was true for plaque rupture, where only 13/30 (43%) had FRS < 9%. (13) Nair, etal, used an ultrafast multislice CAT scan to examine coronary artery plaque and found that in the FRS < 9% group, 44% had proximal plaque formation and 16% had high grade (> 50%) obstruction due to plaque. (14) Proximal plaque was not calcified in 33% of cases. Moreover, of the 106 women with FRS < 9%, 48/106 (45%) had left mainstream or proximal LAD plaque. Abe, etal, used carotid intima-medial thickness and presence of plaque on ultrasound in a community study compared to FRS. Carotid plaque was seen 75/537 (14%) of patients with FRS < 9%, and women made up the bulk of these cases. (15) Finally, in Meteor, of 5751 patients with FRS < 9%, 984 (17%) had substantially increased carotid intima-media thickness on ultrasound. (16) All these studies, and more like them, reveal that people can have subclinical atherosclerosis despite FRS < 9%. The BGS approach has not been analyzed using data from these cited studies. It would be of interest to do such an analysis. The cited studies are examined solely to point out FRS flaws and to suggest that the BGS approach may offer a different means of risk analysis which may better identify people at risk of ATD.

18 Conclusion In light of the preceding discussion, it is clear that the BGS approach agrees well with the FRS for men, though because of the negative points allowed for younger patients, the younger patients with single risk factors disease will be missed by the FRS approach. It is also clear that The BGS approach in women is far superior to the FRS approach and that the superior predictive ability is seen, in women, across all age groups. Indeed, since ATD is the leading cause of death amongst women, it is unacceptable that a risk predictor should assign most women to a low risk group. Although the risk factors involved in either approach are similar, the use of a continuous variable permits better recognition of the population at risk of ATD. It could, of course, be agreed that the FRS was simply designed to predict the risk of future ATD events, but it is common knowledge that older patients have more ATD events than younger patients. No formulation is necessary to confirm this observation. By detecting younger patients at risk of ATD and making detection of the population at risk simpler (CRF-SBP plot position above the threshold line and/or cigarette smoking), the BGS approach is easier to use and hence, is more likely to be used. Finally, it may be argued that it is unfair to compare the FRS and the BGS approaches against the BGS database. However, the FRS and BGS populations are similar, both derive from ATD databases, and the FRS is routinely used to predict risk in populations other than that of Framingham, Mass.

19 References: 1. Lloyd-Jones D, Carnthon M, et al. Heart Disease and Stroke Statistics 2009 Update. A Report From the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation. 2008; DOI: /CIRCULATIONAHA D Agostino RB, Grundy S, Sullivan LM, Wilson P. Validation of the Framingham Coronary Heart Disease Prediction Scores. JAMA. 2001; 286 (2): Toth PP. CHD Risk Estimation in Clinical Practice. Lipid Spin. Summer 2007: 11, Jones P. FRS is not used by many of us. Personal communication with author. Oct. 22, Feeman WE Jr. The Bowling Green Study of the Primary and Secondary Prevention of Atherosclerosis: Descriptive Analysis, Findings, Applications and Conclusions. Ohio J. Sci. 92 (5): Feeman WE Jr. The Bowling Green Study of the Primary and Secondary Prevention of Atherosclerotic Disease: Update Ohio. J. Sci. 94 (4): Feeman WE Jr. Prediction of the Population at Risk of Atherothrombotic Disease. Experimental and Clinical Cardiology. Winter : (4); Feeman WE Jr. Prediction of Angiographic Stabilization/Regression of Coronary Atherosclerosis by a Risk Factor Graph. J. Cardio. Risk. 2000; 7: D Agostino RB, Vasan RS, Pencina MJ, Wolf PA, etal. General Cardiovascular Risk Profile for Use in Primary Care: The Framingham Heart Study. Circulation. 2008; 117: Feeman WE Jr. The Best Lipid Predictor, presented at the 2006 International Atherosclerosis Society Symposium in Rome and the 2008 National Lipid Association

20 Symposium in Seattle. Published in abstract in Atherosclerosis (7/3); 114 and Journal of Clinical Lipidology 2007; 1 (5): Feeman W.E. Jr. The Role of Cigarette Smoking in Atherosclerotic Disease: An Epidemiologic Analysis. J. Cardio. Risk. 1999; 6: Karim R, Hodis HN, Detrano R, Liu C, Liu C, Mack WJ. Relation of Framingham Risk Score to Subclinical Athersclerosis Evaluated Across Three Arterial Sites. Am J Cardiol. 2008; 102: Taylor AJ, Burke AP, O Malley PG, Farb A, etal. A Comparison of the Framingham Risk Index, Coronary Artery Calcification, and Culprit Plaque Morphology in Sudden Cardiac Death. Circulation. 2000; 101: Nair D, Carrigan TP, Curtin RJ, Popovic ZB, etal. Association of Coronary Atherosclerosis Detected by Multislice Computed Tomography and Traditional Risk- Factor Assessment. Am J Cardiol 2008; 102: Abe Y, Rundek T, Sciacca RR, Jin Z, Sacco R. Ultrasound Assessment of Subclinical Cardiovascular Disease in a Community-Based Multiethnic Population and Comparison to the Framingham Score. Am J Cardiol 2006; 98: Crouse JR, Raichlen JS, Riley WA, Evans GW, etal. Effect of Rosuvaststin on Progression of Carotid Intima-Media Thickness in Low-Risk Individuals With Subclinical Atherosclerosis. The METEOR Trial. JAMA. 2007; 297 (12):

21 Table I ATD w/r to ASR Line Above ASR Line Below ASR Line Sex Average Age of + Past - + Past - Male ATD Onset Total Patients Total Patient Years Ave. Age of ATD Onset MSD Onset Total Patients Total Patient Years Ave. Age of ATD Onset Death Total Patients Total Patient Years Ave. Age of ATD Onset Female ATD Onset Total Patients Total Patient Years Ave. Age of ATD Onset MSD Onset Total Patients Total Patient Years Ave. Age of ATD Onset Death Total Patients Total Patient Years Ave. Age of ATD Onset ATD means Atherothrombotic Disease + means Current Cigarette Smoker Past means Former Cigarette Smoker - means Never Cigarette Smoker MSD means Multiple System Disease ASR Line means Angiographic Stabilization/Regression Line

22 Table II BGS VS FRS ATD: BGS + - FRS BGS + ASRL (including CThr) and +/past cigarettes FRS + Risk > 10% BGS: FRS agree 287/336 = 85% BGS +, FRS = 47/49 = 96% BGS: FRS disagree 49/336 = 15% BGS -, FRS + = 2/49= 4% BGS + = 332/336 = 99% If BGS +, FRS - = 285/332 = 86% FRS + = 287/336 = 85% If FRS +, BGS + = 285/287 = 99%

23 Table III BGS VS FRS ATD: BGSFRS FRS BGS + ASRL (including CThr) and +/past cigarettes FRS + Risk > 10% BGS: FRS agree 99/249 = 40% BGS +, FRS = 149/150 = 99% BGS: FRS disagree 150/249 = 60% BGS -, FRS + = 1/150= 1% BGS + = 229/249 = 92% If BGS +, FRS - = 80/229 = 35% FRS + = 81/249 = 33% If FRS +, BGS + = 80/81 = 99% Table IV FRS vs BGS

24 Agree or Disagree Σ ATD: Male Female Rel. Risk Age Agree Disagree Agree Disagree > 20% % < 9% < Σ FRS means Framingham Risk Score BGS means Bowling Green Study ATD means Atherothrombotic Disease Agree means that if FRS predicts risk, BGS predicts risk and if FRS foes not predict risk, BGS does not predict risk. Disagree means that if FRS predicts risk, BGS fails to predict risk, and if FRS does not predict risk, BGS does predict risk. (See Tables II and III for definition of risk prediction) Table V Average Age of ATD Onset

25 w/r FRS Score ATD: Relative Risk < 4% 5-9% 10-19% > 20% Male FRS Points < > 15 Ave Age of ATD Onset No. Patients Total Years Ave. Age , Female FRS Points < > 23 Ave Age of ATD Onset No. Patients Total Years Ave. Age FRS means Framingham Risk Score ATD means Atherothrombotic Disease Relative Risk refers to relative risk of atherothrombotic disease event in the next ten years Table VI BGS + when FRS -

26 Σ ATD: RF Male Female Σ RF Male Female Σ LDL > 170 mg/dl % % % LDL > 170 mg/dl No. Patients Total Years Ave. Age SBP > 180 mmhg % % % SBP > 180 mmhg No. Patients Total Years Ave. Age Diabetes % % % Diabetes No. Patients Total Years Ave. Age CFR > % % % CRF > 0.80 No. Patients Total Years Ave. Age BGS means Bowling Green Study FRS means Framingham Risk Score RF means Risk Factor LDL means low density lipoprotein cholesterol SBP means systolic blood pressure CRF means Cholesterol Retention Fraction BGS + means Bowling Green Study predictive FRS means Framingham Risk Score is not predictive Table VII Discrepancies

27 Σ ATD: Rel. Risk < 9% Cigarettes Threshold Line + Past - Male Above No. Patients Total Years Ave. Age Below No. Patients Total Years Ave. Age Female Above No. Patients Total Years Ave. Age Below No. Patients Total Years Ave. Age Σ Above No. Patients Total Years Ave. Age Below No. Patients Total Years Ave. Age ATD means Atherothrombotic Disease Relative Risk refers to relative risk of atherothrombotic disease event in the next ten years + means current cigarette smokers past refers to a history of cigarette smoking, having quit at least 6 mos. prior to atherothrombotic disease event - means has never smoked cigarettes, but may have used non-cigarette tobacco