Proponents of noninvasive calcium scanning of coronary arteries using electron beam tomography or CT imaging suggest this determination might further refine the selection process for primary prevention. A considerable number of patients with high cholesterol and/or elevated hs-CRP have little or no evidence of calcific plaque when imaged. During a median follow-up of six years, the 25% of patients with baseline coronary artery calcification (CAC) scores >100 accounted for 74% of adverse coronary events. Relatively few events occurred in the 47% of patients with CAC scores of zero. Applying the effect of rosuvastatin (Crestor) treatment from the JUPITER trial to this study population, the NNT to prevent one adverse coronary event was 549 for CAC scores of zero, 94 for scores of 1 to 100, and 24 for scores >100.15 The authors of this analysis argue for low-cost, low-risk, nonpharmacologic intervention in patients with other risk factors but low CAC scores. “These results have important implications for future guidelines and public health discussions aimed at improving the efficiency of statin use in primary prevention.”

The researchers admit, however, that the value of routine use of CAC determination for risk stratification remains to be validated by well-designed, large prospective trials. Additionally, critics of CAC screening argue against its cost, potential harm of radiation exposure, and the risk of unnecessary revascularization procedures when asymptomatic patients are found to have a high plaque burden.

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Is hyperlipidemia justifiably considered a predisease? At the very least, if the finding of high cholesterol or an unfavorable lipid ratio provides a teachable moment to patients, rallying them to lifestyle modification centered around diet and exercise, the campaign may do some good. After all, the benefit may not depend on how low patients get their cholesterol levels to go but how they get there. Nonpharmacologic interventions have the advantage of being cheaper and safer, and they are more likely to achieve real, comprehensive risk factor mitigation.


According to the American Diabetes Association, an estimated 79 million Americans have prediabetes. Once referred to more innocuously as impaired glucose tolerance, prediabetes is defined as: 

  • Fasting blood glucose level between 100 and 125 mg/dL.

  • A two-hour post-challenge blood glucose of 140 to 199 mg/dL on the oral glucose tolerance test

  • A hemoglobin A1c between 5.7% and 6.4%.

A constellation of other factors are predictive of prediabetes, including increased BMI; elevated fasting triglyceride, low HDL, and high uric acid levels; gestational diabetes or a history of giving birth to babies of greater-than-normal birthweight; certain ethnicity or racial backgrounds; sedentary lifestyle; polycystic ovary syndrome; or hypertension.

There are several rationales for identifying and developing criteria for prediabetes. Perhaps foremost is that prediabetes is thought to precede the development of frank diabetes by up to 10 years and heralds its often inevitable natural progression. Additionally, even in the absence of full-blown type 2 diabetes, early pathological changes have been demonstrated in the hearts, brains, kidneys, nerves, and eyes of prediabetic patients. The risk of heart disease, for example, is 1.5 times greater in patients with prediabetes than in those without the disorder. Finally, awareness of prediabetes has the potential to prompt people to delay or prevent the onset of type 2 diabetes through lifestyle changes.

The first confirmation that prevention of frank diabetes might be beneficial comes from the Diabetes Prevention Program (DPP), completed in 2000. The DPP was a major multicenter clinical research study aimed at discovering whether modest weight loss through dietary changes and increased physical activity or treatment with the oral diabetes drug metformin could prevent or delay the onset of type 2 diabetes in study participants.

Patients in the lifestyle-modification arm of DPP were told to eat less fat and fewer calories and to exercise for a total of 150 minutes a week, with the goal of losing seven percent of their body weight and maintaining that loss. After receiving intensive training and motivational support, participants in this arm lowered their risk of developing diabetes by 58%. Subjects receiving 850 mg of metformin b.i.d. also reduced their risk of progression to diabetes, on average, by 31%, but significant benefit was seen mostly in patients younger than age 45 years with BMIs >35, meaning that they were at least 60 lb overweight.16

Given these results, one might reasonably think that even more aggressive pharmacologic targeting of blood sugar in prediabetes would forestall its potential cardiovascular consequences. But the recent Action to Control Cardiovascular Risk in Diabetes (ACCORD) study suggests otherwise.17 Intensive therapy lowered blood sugar in diabetic patients but was fraught with risk: 257 patients in the intensive-therapy group died, as compared with 203 patients in the standard-therapy group. Hypoglycemia requiring assistance and weight gain of more than 10 kg were more frequent in the intensive-therapy group. The study was terminated early. 

A recent reappraisal of ACCORD sought to demonstrate an impact of intensive blood sugar control on the accelerated cognitive decline known to occur in diabetic patients; this analysis also showed no benefit of drug therapy. Therefore, were it to be applied to prediabetic patients, there is every reason to expect that intensive pharmacotherapy would yield an unacceptable risk/benefit ratio. Hence, diet modification and exercise remain the only strongly validated treatments for prediabetes. 


Forty percent of 65-year-old women have osteopenia, a potential precursor to overt osteoporosis, but also in part a mere statistical artifact, since osteopenia is defined as just one standard deviation (SD) below the mean bone density of a healthy 35-year-old woman. With concerns raised over potential risks of hormone replacement, bisphosphonates have come to the forefront of osteoporosis therapy. Among patients with osteopenia, who should be offered medication?