The second study examined TNT participants who had metabolic syndrome, including most of the participants with diabetes. Metabolic syndrome is defined as having at least three of the following: a body-mass index above 28, a fasting plasma glucose over 100 mg/dl, an HDL cholesterol level lower than 40 mg/dl for men and lower than 50 mg/dl for women, a blood pressure at or higher than 135/85 mm Hg, a triglyceride level at or over 150 mg/dl.
As with the previous study of participants with diabetes, those with metabolic syndrome experienced a significant—29%—reduction in risk of major cardiovascular events. In fact, their risk reduction was 7 percentage points greater than that of the overall group.
This study’s authors noted that more than half of the TNT study participants met the criteria for metabolic syndrome. The data from the study shows that they had a 44% increase in absolute risk of major cardiovascular events compared to those without metabolic syndrome, and that those with diabetes were at the highest risk.
Statins and LDL
The trials mentioned here were all conducted with a particular class of drug, the HMG-CoA reductase inhibitors, or “statins.” These include pravastatin, simvastatin, lovastatin, fluvastatin, rosuvastatin, and atorvastatin. There is good reason for investigating these drugs, given their dramatic effect on LDL cholesterol. They are the drugs of choice for reducing the risk of heart disease. In fact, an editorial in the prestigious New England Journal of Medicine suggested that “if ever there were a perfect marriage of drug with disease, it might be between statins and atherosclerosis.”
Early studies of the statins established their usefulness in people with diabetes with dramatic reductions in cardiovascular events. The Heart Protection Study, for instance, used simvastatin and reduced cardiovascular events by about 25% in people with diabetes. Trials of the other statins have had similarly convincing results, with mean reductions in cholesterol of 20%, average reductions in the incidence of coronary artery disease of 30%, and average reductions in mortality of 29%.
The statins also have the bonus effect of lowering triglycerides and raising HDL levels.
There has been concern about the safety of statins because of consistent though rare reports of muscle weakness and aches in people taking statins. The National Lipid Association created a Statin Safety Task Force to investigate the issue, and its report was published in 2006. The authors concluded their review of clinical trials, published case studies, and voluntary notification to regulatory agencies with the statement that “by any standard, statins are remarkably safe drugs.”
Rhabdomyolysis, a breakdown of muscle fibers, was reported to be low in people taking simvastatin, lovastatin, atorvastatin, pravastatin, or fluvastatin, with an estimated incidence of from 3 to a maximum of 7 cases per 100,000 person-years. A more serious muscle condition, myopathy, was attributed to statins at a rate of 11 per 100,000 person-years. The drugs rarely if ever cause liver disease, and no link could be found to kidney disease or cognitive decline. They may cause peripheral neuropathy, a nerve disease that primarily affects the lower limbs, but only at a rate of 12 per 100,000 person-years. (”Person-years” are calculated by adding up the number of years each person in a study or a population has taken a particular drug. For example, if 100 people take drug A for 10 years each, a study of these people would cover 1,000 person-years.)
Blood tests can monitor the development of the muscle-related disorders and provide early warning of developing problems.