A broader measure of atherogenic lipoproteins is total cholesterol minus HDL cholesterol. This measure incorporates some of the triglyceride-rich lipoproteins involved in atherosclerosis. The target is less than 130 mg/dL (TABLE 2).2 All people with borderline (150 to 199 mg/dL) or high (200 mg/dL or above) triglycerides should be managed to achieve this goal. Weight reduction and physical activity are critical, even with drug therapy.
TABLE 2
Comparison of LDL and non-HDL cholesterol goals for 3 risk categories
| RISK CATEGORY | LDL GOAL (MG/DL) | NON-HDL GOAL (MG/DL) |
|---|---|---|
| Coronary heart disease or risk equivalent (10-year risk for coronary heart disease >20%) | ||
| 2 or more risk factors and 10-year risk 20% | ||
| 0–1 risk factor | ||
| LDL = low-density lipoprotein | ||
| HDL = high-density lipoprotein | ||
| Source: NCEP.2 Reprinted with permission | ||
When to use drug therapy
Pharmacologic intervention to lower non-HDL cholesterol may involve use of an LDL-lowering drug or the addition of nicotinic acid or fibrate to reduce VLDL.
When triglyceride levels are extremely high (500 mg/dL or higher), the primary goal of therapy is preventing acute pancreatitis. This may require a combination of low-fat diet, weight loss, regular physical activity, and a triglyceride-lowering drug.2 Once triglyceride levels decline to less than 500 mg/dL, the emphasis can return to reducing cardiovascular risk.
When LDL cholesterol is very high. LDL cholesterol levels of 190 mg/dL or higher, usually signify genetic hypercholesterolemia.2 Early detection—preferably, in young adults—is crucial to prevent coronary heart disease, and a combination of drugs usually is necessary to reduce LDL cholesterol levels. Otherwise, aim for the goals in TABLE 2.
Benefits of statins. In a post hoc analysis of data from the Scandinavian Simvastatin Survival Study, which enrolled patients with elevated LDL cholesterol and coronary heart disease, those with the triad of elevated LDL cholesterol, low HDL cholesterol, and elevated triglycerides were more likely than patients with isolated high LDL cholesterol to have other characteristics of the metabolic syndrome. They also had a greater risk of coronary heart disease on placebo and received greater benefit with simvastatin therapy.15
Fibrates and HDL cholesterol. In a subgroup analysis from the Department of Veterans Affairs High-Density Lipoprotein Intervention Trial, investigators explored the efficacy of gemfibrozil in men with coronary heart disease, HDL cholesterol levels of 40 mg/dL or below, and LDL cholesterol of 140 mg/dL or less.16
Participants were given 1,200 mg of gemfibrozil daily and followed for an average of 5.1 years. The drug was most effective in those with diabetes, reducing death from coronary heart disease by 41% (hazard ratio, 0.59; 95% confidence interval, 0.39–0.91; P<.02>
Among men without diabetes, gemfibrozil was most effective for those in the highest quartile for fasting plasma insulin (risk reduction 35%; P<.04>
Among those who had coronary heart disease and low HDL cholesterol, the drug reduced major cardiovascular events.
Nicotinic acid improves each of the common lipid abnormalities found in metabolic syndrome.17 Early concern that it can precipitate or worsen diabetes has largely been disproved, although some data suggest that it can slightly aggravate insulin resistance and elevate blood glucose.
INTEGRATING EVIDENCE AND EXPERIENCE
The author reports no relevant financial relationships.When it comes to cognitive function, is metabolic syndrome a “brain drain”?
A recent prospective observational study14 found a link between metabolic syndrome and cognitive impairment in the elderly, particularly when inflammation also was present.
Hypertension, diabetes, and other cardiovascular and metabolic risk factors are thought to play a role in the development of Alzheimer’s disease and vascular dementia.
Researchers followed 2,632 elderly men and women over 5 years (mean age: 74), documenting metabolic syndrome in 1,016. Those with metabolic syndrome were more likely to have cognitive impairment (26% versus 21%; multivariate-adjusted relative risk [RR], 1.20; 95% confidence interval [CI], 1.02–1.41) than were those without the syndrome.
Investigators also documented high inflammation in the study population, defining it as higher-than-median serum levels of both interleukin 6 (≥2 pg/mL) and C-reactive protein (≥2 mg/L). They then assessed its relationship to cognitive decline.
Those with both metabolic syndrome and high inflammation had an increased likelihood of cognitive impairment, compared with those without metabolic syndrome (multivariate-adjusted RR, 1.66; 95% CI, 1.19–2.32).
Those with metabolic syndrome and low inflammation had a low likelihood of impairment (multivariate-adjusted RR, 1.08; 95% CI, 0.89–1.30).
These findings held true even after adjusting for demographics, comorbidities, and health habits. It remains to be seen whether attempts to prevent metabolic syndrome or lower inflammation also limit cognitive impairment.