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In this issue:

 The Future of Primary Prevention:
The New Framingham Risk Score and Beyond

From Left to right: Dr. Valentin Fuster introducing the SHAPE Lifetime Achievement Award, Awardees: Dr. Kwame Akosah and Dr. Dan Levy (2nd row) Moderators Dr. Morteza Naghavi, Dr. P.K. Shah and Dr. Roger Blumenthal, Presentor Dr. Rumberger and a snap shot of the room at capacity. 

See event photos & slides

Dr. Harvey Hecht during his presentation on imaging to detect atherosclerosis.

We would like to thank Astra Zeneca
for their generous support of this event.

Aim:

Compare NCEP ATP II and SHAPE guidelines ability in identifying high risk individuals requiring adequate treatment with occult coronary artery disease (CAD).

Methods:

• Study population consisted of 329 asymptomatic Korean subjects who underwent contrast enhance CT angiography (CCTA) for CAD risk evaluation.
• In all individuals, eligibility for LDL lowering therapy was compared according to SHAPE and NCEP ATP III guidelines.

Results:  

• The eligibility of individuals requiring LDL lowering therapy was higher with SHAPE vs. NCEP III guidelines with the differences widening with high CAC scores (CACS>400: 78% vs. 22%).
• Among patients with significant stenosis (≥50%) 61% of individuals reached drug treatment eligibility by SHAPE guidelines compared to 43% with NCEP ATP III (p<0.05)

SHAPE Perspective:

• NCEP ATP III guidelines omit nearly 20.1% of individuals with occult CAD who would be recommended LDL lowering therapy according to SHAPE guidelines.
• The differences became more prominent at among vulnerable individuals with higher atherosclerotic burden, who are the most deserving candidates for aggressive lipid lowering therapy.

TOP

Framingham risk score inadequately predicts risk of acute myocardial infarction
Bertnam Mukete  et al; J am Coll Cardiol 2008; 51:A348

Aim:

To evaluate the Framingham risk score (FRS) and eligibility for statin therapy based on ATP III guidelines among individuals presenting with an acute MI as their first manifestation of coronary artery disease (CAD).

Methods: 

• In this retrospective study, patients without any history of CAD who presented to a large teaching hospital with their first acute MI for years 2004-2006 were analyzed.
• The FRS of all these patients as well statin use status and eligibility were also recorded.

Results:

• The study population consisted of 238 patients meeting study criteria.
• Of these patients 45 (19%) were on statin at the time of presentation of first acute MI.
• Of the reminder 193, only 7% were considered “high-risk” by FRS.
• Overall 80% of these 193 individuals would have not met criteria for drug therapy based on FRS.
• In addition, only half (50%) of those who had met criteria for drug therapy were receiving them.

SHAPE Perspective:

• The study provides further testimony of lack of current risk factor based stratification strategies in identifying high risk individuals and initiating preventive efforts to reduce the occurrence of acute myocardial infarction.
• There is an urgent need to identify cost effective measures to supplement FRS for better identification of these vulnerable individuals as well educating physicians on appropriate use of preventive pharmacotherapy to reduce the likelihood of the catastrophic events.

Framingham risk score underestimates CVD risk among those with peripheral arterial disease
Andrew D Sumner  et al; J am Coll Cardiol 2008; 51:A354

Aim:

To evaluate whether ankle brachial index (ABI) screening is asymptomatic at risk patients identifies high risk CVD patients above and beyond than those with Framingham risk score (FRS)

Methods:

• National Health and Nutrition Examination Surveys (NHANES) data was used for this purpose.
• Study population consisted of 1720 asymptomatic participants (smokers age 50-69 and persons older than 70 years of age)
• Peripheral arterial disease was identified as ABI<0.9

Results: 

• PAD was observed in 11.5% (n=198) of the study population
• Among those with PAD, 52 (26%) were classified as low risk by FRS.
• Women had PAD compared to men while being classified  as low-moderate risk (11.1% vs. 6.3%)

SHAPE Perspective:

• This study provides further evidence to emerging data that FRS appears to underestimate CVD (clinical as well subclinical) risk.
• In addition women are more likely to considered low risk as compared to men in presence of similar atherosclerotic cardiovascular burden.
• Measures of atherosclerotic assessment will improve accurate CVD risk assessment in these vulnerable patient groups.

Aim:

Assess the prevalence of carotid plaque (CP) and femoral plaque (FP) by vascular ultrasound in individuals with low to intermediate risk FRS.

Methods:

• The study population consisted of 484 (46% females) who were screened for CP/FP by ultrasound.
• FRS was determined and those with 10 year risk of CHD <10% were considered as low risk FRS.
• Presence of plaque was defined as >1.5 mm of projection into the lumen.

Results:

• Of 484 subjects, 194 (40%) had either CP or FP.
• Among those with low FRS, 34% had plaque in either one of the territories, whereas 68% had plaque in the intermediate group (FRS 10-20%).
• When only carotid plaques were used as a measurement of atherosclerosis, the respective prevalences in low and intermediate risk groups were only 25% and 53%.

SHAPE Perspective: 

• A significant number of individuals considered low risk by FRS had plaques in carotid and femoral vasculature, representing a missed opportunity for detection of potentially high risk individuals who may benefit from aggressive preventive therapy.
• In addition, this interesting study demonstrating that inclusion femoral vasculature in addition to carotid arteries will identify additional individuals at risk than either alone.

Aim:

Assess the relationship of absence of known major cardiovascular risk factors (CVRF) on subclinical atherosclerosis and inflammation

Methods: 

• The study population consisted of 440 (46±7 years) asymptomatic Brazilian men.
• The individuals were classified according to following risk factors (smoking, SBP≥130 mm of Hg, LDL≥130 mg/fl, HDL<40 mg/dl, triglycerides>150 mg/dl, fasting glucose≥100 mg/dl and waist circumference>102 cm).
• Coronary artery calcification (CAC) and white blood cells (WBC) count were the primary study endpoints

Results:

• Overall 10% of participants had on CVRF, whereas 1,2, 3 and 4 CVRF were seen in 21%, 24%, 19% and 26% respectively.
• Only 18% without any CVRF had CAC, whereas the prevalence with increasing CVRF were 31%, 39%, 45% and 58%.
• Only one person with 0 CVRF had CAC≥100.
• As compared to those with ≥4 CVRF, absence of any risk factor was associated with a significantly lower risk of presence of any CAC (OR: 0.31, 95% CI: 0.12-0.77, p=0.01) as well low probability of high levels of WBC (OR: 0.32, 95% CI: 0.15-0.69, p=0.003)

SHAPE Perspective:

The study finding highlights the importance of primary prevention and supports the notion of very low risk of subclinical CVD among individuals with a favorable CVRF.

Aim:

Assess whether asymptomatic individuals with higher coronary artery calcium (CAC) scores are more likely to utilize Aspirin (ASA)

Methods:

• The study population consisted of 980 asymptomatic individuals undergoing CAC testing.
• These individuals in a mean follow-up of 3 years were reassessed for their lifestyle changes as well medication use.

Results:

• In this study, after nearly 3 years of follow-up, the use of ASA was lowest among those with CAC=0 (26%), whereas increased gradually with higher CAC scores (1-99: 55%, 100-399: 61% and ≥400: 62%, P<0.0001).
• In multivariate analyses adjusting for age, gender and CVD risk factors those with CAC≥400 were nearly 3 times more likely to initiate ASA treatment compared to those CAC=0 (OR: 2.98, 95% CI: 1.83-4.83, p<0.001).

SHAPE Perspective:

• This study demonstrates that a higher CAC scores are not only predictive of adverse CVD, but also improves the utilization of established preventive pharmacotherapy.
• Further studies are needed to confirm if increased medication used in these high risk individuals will translate in improved CVD outcomes.

Aim:

Evaluate the risk of CHD events and associated risk factors among individuals with no detectable coronary artery calcification

Methods:

• The study population was based on  6814 asymptomatic individuals from the multi-ethnic study of atherosclerosis (MESA).
• The individuals were followed for a median of 4.1 years for occurrence of all as well hard CHD events.

Results:

• Overall 189 and 108 all and hard CHD events were reported in this study.
• 3416 (50%) of the study population had no detectable CAC.
• Among individuals with no CAC, 17 (0.49%) and 10 (0.3%) suffered any CHD or hard CHD event respectively.
• On the other hand most of the events occurred among those with CAC.
• Smoking, diabetes mellitus and increased carotid artery intimal medial thickness were associated with increased risk of CHD events in absence of CAC.

SHAPE Perspective:

• The current study provides further strong evidence of the low risk associated with absence of CAC which may suffer as an excellent marker to identify those at very low risk of short-intermediate CHD.
• In addition, efforts should be intensified to aggressively treat those with detectable CAC to reduce long term risk of CHD events.

Aim:

Assess the underlying coronary plaque characteristics among those with increasing CAC scores.

Methods:

The study population consisted of 1043 asymptomatic South Korean who underwent both non contrasts as well contrast CT evaluation for CAC scores and underlying plaque characteristics.

Results: 

• The final study population consisted of 177 (17%) individuals with detectable CAC.
• On contrast enhance CT angiography (CCTA), 32%, 37% and 30% had calcified, mixed and heterogeneous plaques.
• More individuals had heterogeneous plaques with increasing CAC scores (1-10: 19%, 11-100: 37% & >100: 445, p<0.0001) respectively.

SHAPE Perspective:

• The study dispels the notion that increasing CAC scores are more related to calcified plaque burden, but is an excellent indicator of underlying plaque heterogeneity.
• This feature may point to overall plaque burden instability and explain increase events observed with higher CAC scores.

Detection of carotid plaque in absence of coronary calcification may improve CVD risk assessment
Fernando Mendoza et al; J Am Coll Cardiol 2008; 51:A152

Aim:

Determine the presence of carotid plaques across increasing coronary artery calcium scores categories.

Methods: 

• The study population consisted of 136 patients with no history of CVD (mean age: 57 years, 56% females)
• All patients underwent CAC testing and carotid artery ultrasound assessment.
• Carotid plaque (CP) was define as presence of carotid IMT ≥ 1.5 mm with protrusion into carotid lumen

Results:

• Carotid plaque was present in 48% with CAC=0, and in 81% and 89% with CAC=1-99 and ≥100 respectively.
• After taking into account FRS, increasing CACS was significantly associated with presence of CP. The odds of CP with CAC 1-99 vs. CAC=0 was 3.22 (p=0.03) and CAC≥100 vs. CAC=0 was 5.35 (p=0.02).

SHAPE Perspective:

• The data from this interesting study suggest that nearly 50% of individuals without CAC may have underlying carotid plaque.
• Further assessment with CP may improve risk stratification in this group; however it must be kept in mind that the intermediate to long term prognosis in absence of CAC is excellent.
• In order to establish the role of assessing CP on a routine basis in asymptomatic individuals with CAC=0, we n need to provide evidence that it will add to further CVD risk stratification among this very low risk group.

Aim:

Evaluate whether non invasive assessment of vascular function can identify individuals with increase coronary artery disease severity.

Methods:

• The investigators studied 63 patients undergoing contrast enhanced multidetector coronary CT tomography (MDCTA).
• All individuals underwent digital thermal monitoring (DTM) to assess underlying degrees of vascular reactivity.
• After 5 minute of supra systolic arm cuff occlusion, temperature rebound (TR) post occlusion and TMP AUC (area under the curve) was used the measure of vascular reactivity.

Results:

• No difference in baseline temperature was found among those with mild (60%), moderate (19%) and severe (20%) CAD.
• On the other hand TR was significantly lower with increasing CAD severity (P=0.02).
• In logistic regression analyses (adjusting for age, gender and CHD risk factors), the odds ratio of AUC in the lowest tertiles vs. upper 2 tertiles was 1.84 (95% CI: 1.3-2.3, p=0.0001).

SHAPE Perspective:

• Determination of vascular function may contribute to the identification of asymptomatic patients with high burden of coronary artery atherosclerosis. This new technology and others non-invasive vascular function testing can improve existing CVD risk assessment but need further studies for validation and clinical utility.

 The SHAPE Symposium:

  - Event photos & slides

 ACC 08 Science in Review:

  - Summary & perspectives 

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