Practical treatment

There are no established guidelines for treating metabolic syndrome as a whole, so first-line intervention should focus on underlying risk factors. The following strategies are recommended:

  • The NCEP’s Adult Treatment Panel (ATP) III guidelines for lipid management recognize metabolic syndrome and suggest treating obesity, inactivity, hypertension, and lipids.1 HDL and triglycerides are identified as targets after first addressing any elevations in LDL. Similar suggestions are made by the IDF.3 Lipids should be checked and aggressively controlled in patients with metabolic syndrome.
  • FRS may be used in patients with metabolic syndrome as a rough guide for CV risk assessment. Keep in mind, however, that the FRS underestimates such risk in metabolic syndrome.6
  • A rational goal for lipid management in patients with metabolic syndrome would be to treat them as if they already have diabetes or another CHD equivalent (i.e., an LDL goal <100 mg/dL, with a target <70 mg/dL as an option).
  • Low HDL is one of the strongest predictors of CV risk in metabolic syndrome, and patients should be counseled on the dangers of low levels. With isolated low HDL (i.e., without high HDL or triglycerides), drug therapy with nicotinic acid or fibrate should be more strongly considered than it might be in the absence of the metabolic syndrome.1 While cholesteryl ester transfer protein inhibitors (e.g., torcetrapib) and other approaches show great promise in raising HDL, they are not yet available.13
  • To reduce risk from the prothrombotic state induced by metabolic syndrome, patients with no contraindications should be placed on low-dose aspirin.
  • Because hypertension may be the most significant risk factor for development of CVD, a BP goal <130/80 should be aggressively pursued, as suggested by the ADA and JNC 7 report for diabetic patients.10,14
  • A healthy diet and exercise should be strongly encouraged. This can improve CV fitness, increase weight loss and insulin sensitivity, decrease BP, and improve lipid metabolism. Overweight patients should be counseled on the importance of losing weight and achieving a normal BMI, and all patients should be urged to participate daily in 30-45 minutes of moderate exercise (e.g., walking). In addition, increasing the level of activity better promotes weight loss and may confer higher CV fitness (i.e., losing 7% of initial body mass and participating in 150 minutes/week of moderate-intensity exercise can help prevent diabetes and reduce metabolic syndrome risk factors).15
  • Because smoking plays a significant role in the progression of CVD, cessation is paramount for those patients with the metabolic syndrome.

Pharmacologic therapies

Although no drugs have been approved specifically for treating metabolic syndrome, individual elements of the syndrome should be addressed as they occur. In addition, some medications may provide particular benefit in treating specific elements of the syndrome. In particular, drug therapy that may prevent the development of diabetes has been examined in numerous studies.16

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A number of studies have shown that ACE inhibitors reduce the risk for developing diabetes in patients with prediabetes and metabolic syndrome.17 Although the mechanism of this prophylactic effect is unclear, prevention of progression to diabetes should confer a concomitant decrease in CV risk. Therefore, in patients with metabolic syndrome and poorly controlled hypertension, an ACE inhibitor would be a rational first choice of antihypertensive. Of note, JNC 7 guidelines do not consider metabolic syndrome to be a “compelling indication” for the use of ACE inhibitors.10

Insulin sensitizers (thiazolidinediones) reduce insulin resistance, inflammatory markers, and risk for progression in prediabetes.18-20 

Metformin clearly decreases progression to diabetes in prediabetic patients,21 but its role in decreasing insulin resistance and reducing risk of CVD in diabetes is less clear.22 It has been shown, however, that lifestyle modifications are superior to metformin in reducing multiple risk factors, including BP, low HDL, and atherogenic small dense LDL.22

Statins reduce prothrombotic tendencies, decrease inflammation, and certainly lower risk for developing CHD. But do they have any effect on progression of the metabolic syndrome? A single trial has suggested a possible preventive effect of statin drugs on the development of diabetes,23 but this has not been confirmed by other studies. Despite this unclear relationship to prevention of diabetes, however, the statins’ very significant effects on prevention of CVD warrant their use in any patient with elevated LDL or increased CV risk.

Judicious use of ACE inhibitors to treat hypertension and statins to treat hyperlipidemia in patients with the metabolic syndrome are clearly appropriate at this time. The use of metformin and insulin sensitizers is likely to reduce progression and CV risk in the metabolic syndrome, but such use has not achieved acceptance within the medical community. Future studies of these agents will be of great interest to ascertain their appropriate use in patients who are not frankly diabetic.

Take-home lesson

While there is still confusion over what symptoms comprise metabolic syndrome — or even if there actually is such a condition — it is important to remember that patients with the metabolic syndrome are at greater risk for CVD as well as diabetes, and the more components of the condition are present, the higher the risk. Unfortunately, there is no simple strategy for treating this disease, so the best option is to treat the individual components as they appear.

Dr. Hadley is associate professor, Department of Clinical Sciences, Division of Physician Assistant Studies, at the University of Kentucky in Lexington.


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