Metabolic syndrome
LASACH02.sys
Miranda Dik (dd. 13-04-2011)
Christa van Bunderen (dd. 30-12-2011)
Background
The clustering of risk factors such as hypertension, obesity, dyslipidemia, and hyperglycemia, has recently been introduced as the concept of the metabolic syndrome. The metabolic syndrome is very common, especially among older persons, with a prevalence of 45% at the age of 60 years and over (1). The metabolic syndrome has been shown to increase the risk of diabetes mellitus and cardiovascular disease (CVD). Since its introduction in 1998, the metabolic syndrome has been subject to a large amount of research, and an even larger amount of discussion about the validity and utility of the concept (2). The metabolic syndrome often co-occurs with an increased inflammatory response, although it is unknown whether the metabolic syndrome leads to increased inflammation or vice versa.
Measurement in LASA
Metabolic syndrome
The definition established by the US National Cholesterol Education Program (NCEP)-ATPIII (3) is used with few modifications. The metabolic syndrome was defined as a presence of 3 or more of the following criteria:
- Triglycerides ³ 1.7 mmol/L (150 mg/dl) *
- HDL cholesterol < 1.0 mmol/L (40 mg/dl) for men, <1.3 mmol/L (50 mg/dl) for women *
- Blood pressure ³ 160/90 mmHg or antihypertensive medication **
- Waist circumference >102 cm for men and >88 cm for women ***
- Fructosamine ³ 247 mmol/L or antidiabetic medication ****
* Because the instructions before blood sampling allowed subjects to take tea and plain toast, we could not guarantee fasting blood samples. Triglycerides, and to a lesser extend HDL cholesterol, could be affected. However, it has been demonstrated that lipid profiles change minimally in response to normal food intake, and nonfasting levels still predict cardiovascular events (4).
** An increased cutoff for blood pressure is used, adjusted for an older population (systolic ³160 or diastolic ³90). If we used 130/85 mmHg (as definition) almost 90% of the subjects would be hypertensive. This lower cutoff would not discrimate between the groups. In hypertension trials with elderly, higher cutoff values are often used (5;6).
Antihypertensive medication: In the file: LASACH02.sys, for the component hypertension diuretics have not been included as antihypertensive medication. The rationale at time (M. Dik) was the high number and the risk for misclassification (e.g. other indication for diuretic use). Nevertheless, diuretics are the first choice treatment for hypertension in elderly. To include diuretics, these subjects can be identified in the file LASAC152/352. In the study of van Bunderen et al. (2012), this meant 44 more subjects fullfilling the criteria of hypertension (62.7 à 65.7%) and eventually 8 more subjects with the metabolic syndrome (in a total of 1258 subjects).
*** At cycle C (1995/1996) there are a number of missing values for waist circumference. In the syntax of metabolic syndrome these missings have been imputed using BMI measurement corrected for age and sex (see LASACH02_metabolic syndrome.sps).
**** The cutoff of 247 mmol/L for fructosamine corresponds to the cutoff of 6.1 mmol/L for fasting plasma glucose in terms of sensitivity and specificity in discriminating subjects with glucose intolerance from subjects with normal glucose tolerance (7). Because the instructions prior to blood sampling allowed respondents to take tea and dry toast, but no dairy products, we cannot guarantee fasting blood samples. Fructosamine is little affected by eating, unlike the plasma glucose level. Therefore, we used serum fructosamine as a proxy for plasma glucose.
Assessment of components of the metabolic syndrome
Blood pressure was measured in sitting position using a standard mercury sphygmomanometer. Waist circumference was calculated as the average of two measurements measured to the nearest 0.1 cm midway between the lower rib margin and the iliac crest following a normal expiration. History of pharmacological medication was obtained using the drug inventory method (identification of prescription drugs taken in the previous two weeks).
Fructosamine was determined by a colorimetric test, and HDL cholesterol and triglycerides by an enzymatic colorimetric test (Roche diagnostics, Mannheim, Germany). The interassay coefficient of variation was <2.8% for fructosamine and triglycerides, and <6.4% for HDL cholesterol. All laboratory analyses (HDL cholesterol, triglycerides, and fructosamine) were performed in EDTA plasma samples stored at –80° C, at the Department of Clinical Chemistry of the VUmc in 2005.
Prevalence of (components of) the metabolic syndrome in LASA
The prevalence of the metabolic syndrome in LASA among participants aged 65-88 years is 37.8%, in line with reported prevalence in the literature (1;8). The prevalence of the individual components of the metabolic syndrome in LASA is: 52.1% for abdominal obesity, 62.8% for hypertension (without diuretics), 31.6% for high triglycerides, 36.4% for low HDL cholesterol, and 25.4% for hyperglycemia.
Use in LASA
Studies on associations of (components of) the metabolic syndrome with cognitive decline (M. Dik), depression (B. Penninx / N. Vogelzangs), serum 25-hydroxyvitamin D (M. Oosterwerff), and serum insulin-like growth factor-I / CVD (C. van Bunderen) have been conducted.
Reference List
(1) 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 Jan 16;287(3):356-9.
(2) Kahn R, Buse J, Ferrannini E, Stern M. The metabolic syndrome: time for a critical appraisal: joint statement from the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 2005 Sep;28(9):2289-304.
(3) 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 May 16;285(19):2486-97.
(4) Langsted A, Freiberg JJ, Nordestgaard BG. Fasting and nonfasting lipid levels: influence of normal food intake on lipids, lipoproteins, apolipoproteins, and cardiovascular risk prediction. Circulation 2008 Nov 11;118(20):2047-56.
(5) Dahlof B, Lindholm LH, Hansson L, Schersten B, Ekbom T, Wester PO. Morbidity and mortality in the Swedish Trial in Old Patients with Hypertension (STOP-Hypertension). Lancet 1991 Nov 23;338(8778):1281-5.
(6) Staessen JA, Fagard R, Thijs L, Celis H, Arabidze GG, Birkenhager WH, et al. Randomised double-blind comparison of placebo and active treatment for older patients with isolated systolic hypertension. The Systolic Hypertension in Europe (Syst-Eur) Trial Investigators. Lancet 1997 Sep 13;350(9080):757-64.
(7) Herdzik E, Safranow K, Ciechanowski K. Diagnostic value of fasting capillary glucose, fructosamine and glycosylated haemoglobin in detecting diabetes and other glucose tolerance abnormalities compared to oral glucose tolerance test. Acta Diabetol 2002 Apr;39(1):15-22.
(8) McNeill AM, Katz R, Girman CJ, Rosamond WD, Wagenknecht LE, Barzilay JI, et al. Metabolic syndrome and cardiovascular disease in older people: The cardiovascular health study. J Am Geriatr Soc 2006 Sep;54(9):1317-24.