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.
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
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.
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.
- Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA. 2001;285:2486-2497.
- Hunt KJ, Resendez RG, Williams K, et al. National Cholesterol Education Program versus World Health Organization metabolic syndrome in relation to all-cause and cardiovascular mortality in the San Antonio Heart Study. Circulation. 2004;110:1251-1257.
- International Diabetes Foundation. The IDF consensus worldwide definition of the metabolic syndrome.
- Carr DB, Utzschneider KM, Hull RL, et al. Intra-abdominal fat is a major determinant of the National Cholesterol Education Program Adult Treatment Panel III criteria for the metabolic syndrome. Diabetes. 2004;
- Ford ES, Giles WH, Dietz WH. Prevalence of the metabolic syndrome among US adults: findings from the third National Health and Nutrition Examination Survey. JAMA. 2002;287:356-359.
- McNeill AM, Rosamond WD, Girman CJ, et al. The metabolic syndrome and 11-year risk of incident cardiovascular disease in the atherosclerosis risk in communities study. Diabetes Care. 2005;28:385-390.
- Isomaa B, Almgren P, Tuomi T, et al. Cardiovascular morbidity and mortality associated with the metabolic syndrome. Diabetes Care. 2001;24:683-689.
- Lakka HM, Lakka TA, Tuomilehto J, et al. Hyperinsulinemia and the risk of cardiovascular death and acute coronary and cerebrovascular events in men: the Kuopio Ischaemic Heart Disease Risk Factor Study. Arch Intern Med. 2000;160:1160-1168.
- Adler AI, Stratton IM, Neil HA, et al. Association of systolic blood pressure with macrovascular and microvascular complications of type 2 diabetes (UKPDS 36): prospective observational study. BMJ. 2000;321:412-419.
- Chobanian AV, Bakris GL, Black HR, et al. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA. 2003;289:2560-2572.
- Ridker PM, Wilson PW, Grundy SM. Should C-reactive protein be added to metabolic syndrome and to assessment of global cardiovascular risk? Circulation. 2004;109:2818-2825.
- Hadley RD, Graber MA. Should we measure CRP levels to assess cardiovascular risk? JAAPA. 2003;16:17-19.
- Brousseau ME, Schaefer EJ, Wolfe ML, et al. Effects of an inhibitor of cholesteryl ester transfer protein on HDL cholesterol. N Engl J Med. 2004;350:1505-1515.
- American Diabetes Association. Standards of medical care in diabetes. Diabetes Care. 2005;28:S4-S36.
- The Diabetes Prevention Program (DPP) Research Group. The Diabetes Prevention Program (DPP): description of lifestyle intervention. Diabetes Care. 2005;28:736-744.
- Padwal R, Majumdar SR, Johnson JA, et al. A systematic review of drug therapy to delay or prevent type 2 diabetes. Diabetes Care. 2005;28:736-744.
- Inzucchi SE, Sherwin RS. The prevention of type 2 diabetes mellitus. Endocrinol Metab Clin North Am. 2005;34:199-219.
- Haffner SM. Pre-diabetes, insulin resistance, inflammation and CVD risk. Diabetes Res Clin Pract. 2003;61 Suppl 1:S9-S18.
- Mizushige K, Tsuji T, Noma T. Pioglitazone: cardiovascular effects in prediabetic patients. Cardiovasc Drug Rev. 2002;20:329-340.
- Buchanan TA, Xiang AH, Peters RK, et al. Preservation of pancreatic beta-cell function and prevention of type 2 diabetes by pharmacological treatment of insulin resistance in high-risk Hispanic women. Diabetes. 2002;51:2796-2803.
- Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002;346:393-403.
- Ratner R, Goldberg R, Haffner S, et al. Impact of intensive lifestyle and metformin therapy on cardiovascular disease risk factors in the Diabetes Prevention Program. Diabetes Care. 2005;28:888-894.
- Freeman DJ, Norrie J, Sattar N, et al. Pravastatin and the development of diabetes mellitus: evidence for a protective treatment effect in the West of Scotland Coronary Prevention Study. Circulation. 2001;103: