Paolo Raggi

Cardiovascular disease is the most frequent cause of death and disability in diabetes, and the morbidity and mortality for coronary artery disease (CAD) in this population is two to four times higher than in nondiabetic subjects. Traditional risk factors do not fully explain the level of cardiovascular risk, and coronary disease events are often silent in diabetic patients. Thus, research has recently focused on improving the risk assessment of an individual patient with new tools in an effort to better identify subjects at highest risk and in need of aggressive management. Cardiovascular imaging has proven very helpful in this regard. Traditional methods to assess CAD are based on detection of obstructive luminal disease responsible for myocardial ischemia. However, acute coronary syndromes often occur in the absence of luminal stenoses. Hence, the utilization of imaging methodologies to visualize atherosclerosis in its presymptomatic stages has received mounting attention in recent years. In this article, we review the current literature on the utility of traditional imaging modalities for obstructive CAD (nuclear and echocardiographic stress testing) as well as atherosclerosis plaque imaging with carotid intima-media thickness and coronary artery calcium for risk stratification of diabetic patients.

Cardiovascular disease is the first cause of morbidity and mortality for both men and women in developed countries. Tracking the progression of the atherosclerotic plaque appears to be an effective way to predict modification of risk in individual patients. Quantitative coronary angiography was initially proposed as a method of choice to assess coronary disease progression. With this methodology it was possible to demonstrate a strong association of plaque regression with reduction in adverse cardiovascular outcomes. More recently, the focus of research has turned to the development of noninvasive modalities to image the atherosclerotic plaque in its preclinical stages and to evaluate the effectiveness of preventive therapies with sequential imaging. The ease of performance of these tests enabled their use as intermediate endpoints in clinical trials to test new strategies to treat atherosclerosis. If proven successful, these imaging tools may allow a reduction in size and duration of clinical trials with a substantial cost benefit for society.

Background— Women have been underrepresented in statin trials, and few data exist on the effectiveness and safety of statins in this gender. We used sequential electron-beam tomography (EBT) scanning to quantify changes in coronary artery calcium (CAC) as a measure of atherosclerosis burden in patients treated with statins. Methods and Results— In a double-blind, multicenter trial, we randomized 615 hyperlipidemic, postmenopausal women to intensive (atorvastatin 80 mg/d) and moderate (pravastatin 40 mg/d) lipid-lowering therapy. Patients also submitted to 2 EBT scans at a 12-month interval (mean interval 344±55 days) to measure percent change in total and single-artery calcium volume score (CVS) from baseline. Of the 615 randomized women, 475 completed the study. Mean±SD percent LDL reductions were 46.6%±19.9% and 24.5%±18.5 in the intensive and moderate treatment arms, respectively ( P P P =NS), and single-artery CVS% changes and absolute changes were also similar ( P =NS). In both arms, there was a trend toward a greater CVS progression in patients with prior cardiovascular disease, diabetes mellitus, and hypertension, whereas hormone replacement therapy had no effect on progression. Conclusions— In postmenopausal women, intensive statin therapy for 1 year caused a greater LDL reduction than moderate therapy but did not result in less progression of coronary calcification. The limitations of this study (too short a follow-up period and the absence of a placebo group) precluded determination of whether progression of CVS was slowed in both arms or neither arm compared with the natural history of the disease.

Progression of coronary artery calcium, a marker of atherosclerosis, can be slowed with statins, and continued progression of calcium is associated with an increased risk of myocardial infarction. However, it is not known whether statins are effective in slowing calcium progression in diabetes mellitus. In a retrospective study, we examined 1153 nondiabetic and 157 diabetic subjects who underwent sequential electron beam tomography scans at a minimum 1-year interval to assess progression of coronary calcium. A yearly score increase >15% was considered evidence of true progression. The use of statins and occurrence of myocardial infarction were recorded. There was no difference in baseline calcium score between diabetic and nondiabetic patients. Diabetic patients with no coronary calcium on the baseline scans developed it more often than nondiabetic subjects (42% versus 25%; P =0.046) during follow-up. Calcium progression was 33% greater in diabetic patients than nondiabetic subjects ( P P P <0.001). In logistic models, diabetes mellitus and systemic hypertension were the best predictors of calcium progression (odds ratio, 3.1 and 1.9, respectively), whereas baseline calcium score percentile and statin therapy were the best predictors of infarction. These findings support the notion that diabetes mellitus causes accelerated atherosclerosis, even in the presence of statin therapy, and provide evidence that coronary calcium monitoring is an effective method to assess treatment efficacy.

Cardiovascular disease is the most common cause of death in the Western hemisphere, and in the majority of cases the event announcing the presence of atherosclerosis is either sudden death or a disabling myocardial infarction or stroke. Although traditional risk factors are present in most individuals suffering a cardiovascular event, the prognostic ability of risk factors to predict events in the short term is limited. The focus of research has therefore turned to the application of noninvasive modalities to image the atherosclerotic plaque in its preclinical stages. Measurements of coronary artery calcium serve as a quantitative reflection of the severity of coronary artery disease, and greater calcium burdens correlate with more advanced disease. Coronary artery calcium has been shown in several studies to add prognostic value to traditional risk factors in patients at intermediate risk, and in this group of patients it may be cost effective. There is, however, an inherent danger in raising the cost of...

Objective— Statins reduce cardiovascular risk and slow progression of coronary artery calcium (CAC). We investigated whether CAC progression and low-density lipoprotein (LDL) reduction have a complementary prognostic impact. Methods and Results— We measured the change in CAC in 495 asymptomatic subjects submitted to sequential electron-beam tomography (EBT) scanning. Statins were started after the initial EBT scan. Myocardial infarction (MI) was recorded in 41 subjects during a follow-up of 3.2±0.7 years. Mean LDL level did not differ between groups (118±25 mg/dL versus 122±30 mg/dL, MI versus no MI). On average, MI subjects demonstrated a CAC change of 42%±23% yearly; event-free subjects showed a 17%±25% yearly change ( P =0.0001). Relative risk of having an MI in the presence of CAC progression was 17.2-fold (95% CI: 4.1 to 71.2) higher than without CAC progression ( P 15% per year ( P Conclusions— Progression of CAC was significantly greater in patients receiving statins who had an MI compared with event-free subjects despite similar LDL control. Continued expansion of CAC may indicate failure of some patients to benefit from statin therapy and an increased risk of having cardiovascular events.