66-Year-Old Female With the Metabolic Syndrome

	Peter W. F. Wilson, MD

The following case was provided by NLEC Faculty Member Peter W. F. Wilson, MD, Professor of Medicine, Section of Endocrinology, Nutrition, and Diabetes, Boston University School of Medicine, and Director of Laboratories, Framingham Heart Study.

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ME, a 66-year-old white female, presents with no specific complaints for a regular checkup. She has been overweight all of her adult life; her weight has been as high as 200 lb and as low as 160 lb during the past 5 years. She walks 10 minutes per day to the commuter bus and enjoys occasional 30-minute weekend walks with her friends (this is her only exercise). She smoked five cigarettes per day until 3 years ago, when she quit. She takes no medications.
    Family history includes two older siblings who are overweight; one of them takes metformin for recently diagnosed type 2 diabetes. Neither sibling has vascular disease. Her mother died of breast cancer at age 78, and her father died from a stroke at age 70.

Discussion
This patient presents with several features of the metabolic syndrome (Table 1). Given the evidence-based literature, you are greatly concerned about her risk for clinical heart disease and type 2 diabetes.^1-3 She is obese (BMI >30 kg/m²) and has an increased waist circumference, low HDL-C, increased TG, and impaired fasting glucose (per 1997 American Diabetes Association [ADA] criteria).⁴ This patient has none of the major conditions associated with elevated LDL-C, such as hypothyroidism, obstructive liver disease, renal insufficiency, or steroid medication use (Table 2).
    As a first step, you count her risk factors according to the National Cholesterol Education Program's Third Report of the Adult Treatment Panel (NCEP's ATP III) (smoking, hypertension, low HDL-C, premature CHD in a first-degree relative, age). She reports no cigarette smoking in the past year and is classified as a nonsmoker. She has a total of two risk factors: age (>55 years for a woman) and low HDL-C. As she has >2 risk factors, the next step is to calculate her 10-year estimated risk for hard CHD events (ie, the risk for an MI or coronary death) according to the Framingham risk scoring system included in ATP III. You estimate her risk as follows: 66 years of age (12 points), TC 220 mg/dL (2 points), nonsmoker (0 points), HDL-C 38 mg/dL (2 points), systolic BP 128 mm Hg (1 point). This totals 17 points, or a 5% risk over 10 years. Although she is below the 20% per 10-year CHD threshold identified as high risk by ATP III, ME is at increased risk for coronary disease (5% over 10 years) compared with a woman the same age who has good levels (1% risk over 10 years) (Figure).



    It is important to note that Framingham equations published in 1998 estimate risk for total CHD, which includes angina pectoris, MI, and coronary death.⁵ The 2001 Executive Summary Report of NCEP's ATP III is based on the experience of Framingham participants and estimates risk of hard CHD; it does not include angina pectoris. According to the recent literature, the Framingham experience generally applies to most population groups across the United States.⁶
    The LDL-C goal for this patient with >2 risk factors and a 10-year risk in the <10% range is LDL-C <130 mg/dL (Table 3). Her current LDL-C is 134 mg/dL—slightly above the target range. Therapeutic lifestyle changes with counseling for diet, weight loss, and increased physical activity are appropriate first steps. The patient should be reevaluated at 6 weeks with a follow-up fasting lipid profile. Should the LDL-C level be >130 mg/dL at the return visit, it would be appropriate to continue TLC and initiate lipid medication.



    While meeting with a dietitian, ME was instructed in an American Heart Association Step I diet (7% calories saturated fat, cholesterol <200 mg/day) at an intake level of 1,200 calories/day. The dietitian explained that ME has probably been eating 1,700 to 1,800 calories/day to sustain her 180-lb weight. The patient was told that a decrease of 500 calories/day—a diet containing 1,200 to 1,300 calories/day—would lead to a weight loss of approximately 1 lb/week and that favorable effects on her metabolic profile typically would be seen with as little as 5 to 10 lb of sustained weight reduction.^7,8 She understood the dietitian's advice and was able to cut out some of the "empty calories," such as fruit juices and soda, but admitted there was much more to be done.
    At 6 weeks, ME returns for her follow-up. She says that she's been able to take 30-minute walks at the mall on the weekends but is too busy working to do anything more. Her weight is now 178 lb, fasting glucose 112 mg/dL, TC 207 mg/dL, HDL-C 37 mg/dL, TG 210 mg/dL, and her calculated LDL-C 128 mg/dL.
    Although this patient is not at the highest risk of heart disease over the next 10 years, you are nonetheless concerned about a variety of borderline abnormalities—the metabolic syndrome. She has four of the five features that have been used to characterize the metabolic syndrome³: an increased abdominal girth, high TG, low HDL-C, and impaired fasting glucose (the ADA defines impaired fasting glucose as 110–125 mg/dL). Diet, weight loss, and increased physical activity are key to improving her metabolic risk profile, but it is clear that she has not made much progress.
    Triglyceride levels >150 mg/dL are now considered one of the criteria for the metabolic syndrome according to ATP III, and ME's level of 210 mg/dL is in the high range. ATP III recommends that non–HDL-C be considered a secondary target of therapy in these patients. (Because non–HDL-C contains all known and potential atherogenic lipid particles, it is increasingly being viewed as a reliable possible predictor of risk for cardiovascular disease, as LDL-C is presently.⁹ Non–HDL-C is calculated as TC minus HDL-C; the non–HDL-C goal is set at 30 mg/dL higher than that for LDL-C.³) As seen in Table 3, she has a non–HDL-C target <160 mg/dL, and her current level is 170 mg/dL. She has not reached the non–HDL-C goal with lifestyle changes, so it is appropriate to begin lipid therapy with a statin.
    Some experts would also consider this lipid profile a good indication for fibrate therapy, as data from the Veterans Affairs Cooperative Studies Program High-Density Lipoprotein Cholesterol Intervention Trial (VA-HIT) showed that recurrent coronary artery disease was less likely in men with low HDL-C and high TG when treated with gemfibrozil.¹⁰ It is likely that a starting dose of one of the statin preparations would decrease her non–HDL-C below the target level of 160 mg/dL; she is already at the LDL-C goal before this therapy is initiated. You mention to her that such therapy is not treating all aspects of the metabolic syndrome, but that it should lower her CHD risk. You tell the patient that you are particularly concerned she shows up for her follow-up clinic visits, stays on her lipid medication, incorporates more exercise into her daily routine, and loses weight.

Comment
ME is at intermediate risk for coronary artery disease. Because she has several features of the metabolic syndrome, including low HDL-C and high TG, she is targeted for more aggressive therapy than might normally be expected. Lifestyle and pharmacologic interventions are indicated to reduce LDL-C and non–HDL-C to the goal ranges. Additionally, this patient will need to be followed assiduously for the development of type 2 diabetes.

References