Treatment options for metabolic syndrome

Treat for components that are also stroke risk factors.
Treat for components that are also stroke risk factors.

At a glance

  • The National Cholesterol Education Program defines metabolic syndrome as the presence of at least three of five symptoms: hypertension, low HDL, elevated triglycerides, abdominal obesity, and glucose intolerance. Abdominal obesity is considered the most important risk factor.
  • Cardiovascular risk in patients with metabolic syndrome has been estimated at two to three times that of those without the syndrome.
  • A rational goal for lipid management in patients with metabolic syndrome would be to treat them as if they already have diabetes or another coronary heart disease equivalent.
  • ACE inhibitors are a rational first choice of anithypertensives in patients with metabolic syndrome and poorly controlled hypertension.

Metabolic syndrome was defined in 1998 by the World Health Organization as a constellation of metabolic derangements that place patients at higher risk for cardiovascular (CV) events. The National Cholesterol Education Program (NCEP) modified that definition to the presence of at least three of five metabolic abnormalities — hypertension, low HDL, elevated triglycerides, abdominal obesity, and glucose intolerance.1 Most U.S. clinicians use the NCEP guidelines, which may be more effective for predicting CV risk.2

In April 2005, the International Diabetes Foundation (IDF) developed yet another definition of metabolic syndrome.3 Unlike those provided by the NCEP, IDF guidelines offer ethnic-specific definitions of abdominal obesity and include this form of obesity as a necessary component. In addition, cutoffs for abdominal obesity are somewhat lower than those provided by the NCEP (e.g., ≥37 in vs. >40 in for Caucasian men). Research has shown that abdominal obesity is one of the most important risk factors for metabolic syndrome.4 To what extent the IDF definition will be adopted worldwide is not yet known.


Incidence of metabolic syndrome increases with patient age and obesity. Only about 7% of patients age 20 and younger meet the current criteria. By the time patients reach age 60, >40% meet the criteria.5 Hispanic and African-American patients have the greatest risk for developing metabolic syndrome, followed by Caucasians. Asians have the lowest risk, at least in the United States.

Morbidity risks

Metabolic syndrome involves peripheral insulin resistance and the existence of a prothrombotic, atherogenic state. Not only are patients at high risk for CVD, but also for diabetes. CV risk in people with the metabolic syndrome has been estimated at approximately two to three times that of those without the syndrome. In addition, those with multiple symptoms appear to have graded, increasing risk for CV events. While this effect is greater in women than in men, it is significant in both genders. Women with four or more components of the metabolic syndrome have a five times greater risk for coronary heart disease (CHD) than those without any components.6

Risk-factor development

It is not clear which, if any, of the individual factors contributes most to risk for CV events. Some experts have suggested that in patients with metabolic syndrome, the additional presence of microalbuminuria is the strongest predictor of eventual negative CV outcomes.7 The development of microalbuminuria is influenced by various factors, including BP, lipid derangements, and hyperglycemia, possibly explaining why such renal impairment predicts CVD so well. Abdominal obesity is a better predictor than glucose intolerance of whether a patient will develop metabolic syndrome, but it is not necessarily a better predictor of CV risk.4 Currently, there is no evidence to suggest that any one specific aspect of metabolic syndrome affects risk of CVD or diabetes more than the other, although insulin resistance and hyperinsulinemia may be precursors to CVD independent of other risk factors.8 Insulin resistance may be affected by a number of factors in metabolic syndrome. Ultimately, clinicians are faced with the task of recognizing and addressing each component in order to lower global CV risk.

The Atherosclerosis Risk in Communities (ARIC) study showed that elevated BP and low HDL were associated with higher hazard ratios for development of CHD than were the other elements of the metabolic syndrome.6 This study involving >5,000 men and nearly 7,000 women, all of either Caucasian or African-American descent, suggests that elevated BP should be a primary target for treatment in metabolic syndrome as it is in diabetes.9,10

Risk assessment

In addition to considering the five diagnostic criteria, global CV risk assessment may be assisted by measurement of other lipids (e.g., LDL, non-HDL lipids) or by use of some newer laboratory measurements that relate to risk. The high-sensitivity C-reactive protein (hs-CRP) test has been proposed as a useful adjunct to current assessment tools and may be of particular use in assessing patients with apparently moderate risk.11,12 Patients with clearly elevated LDL should be treated with a statin regardless of hs-CRP levels, and treatment plans would not be changed by obtaining hs-CRP levels. There are no recommendations to treat elevated hs-CRP levels in the absence of any other CV risk.11

Use of the Framingham Risk Scores (FRS), which estimate the risk of developing CHD within a 10-year time period, can be misleading, since patients with metabolic syndrome and moderate FRS are at higher risk for CVD than patients with the same FRS who do not have metabolic syndrome.6

There are no recommendations specific to metabolic syndrome about how often risk indicators should be measured. If treatment changes have been instituted to address specific components of the syndrome and the response has been effective (e.g., treatment of elevated lipids), monitoring of the patient's response should follow normal recommendations (e.g., every four to six months for lipids).1 If the response is not stable and at goal, monitoring should be more frequent. Other studies, such as ankle-brachial indices and ECGs, should be used periodically to assess global CV risk, with the results assisting in the decision whether to continue current therapy or to more aggressively pursue the causes of that risk.

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