Abdominal
Obesity Is Associated With an Impaired Fibrinolytic Elevated Plasminogen Activator Inhibitor-l
Kerstin Landin, Lennart Stigendal,
Elsa Eriksson,
Marcin Krotkiewski,
Activity
60 Risberg, Lilian Tengborn,
and
and Ulf Smith
Recent epidemiologic studies have shown that abdominal obesity, characterized by a high waist to hip circumference ratio (WHRL is associated with increased cardiovascular morbidity and mortality. The present study examines components of the fibrinolytic system in obese and lean middle-aged women with a high and low WHR. Ten women in each group were carefully matched with respect to age, body weight, lean body mass, and body fat. Fibrinogen and endothelial type of plasminogen activator inhibitor-l (PAI- j were significantly elevated in the obese women with a high WHR compared with the obese women with a low WHR or with both groups of lean women. In addition, obese women with a high WHR exhibited a greater metabolic risk profile (elevated glucose, insulin, and triglyceride levels). When all subjects were pooled for the analyses, both fibrinogen and PAIlevels correlated positively with glucose and insulin levels. PAI- was also negatively related to degree of insulin sensitivity measured with the euglycemic clamp technique. In the obese groups, WHR but not body mass index (BMI), correlated with PAI- levels. No such correlations were seen in the lean groups. In conclusion, the data show that a high WHR in obese, but not lean middle-aged women, is associated with an impaired fibrinolytic activity. This perturbation becomes enhanced when it is associated with hyperinsulinemia and insulin resistance, which is a typical feature of abdominal obesity. @ 1990 by W. B. Saunders Company.
R
ECENT STUDIES have shown that the distribution of the adipose tissue, in addition
to the amount of body fat, is an important determinant of morbidity and mortality.‘.* Both for lean and obese individuals, relative abdominal preponderance of the adipose tissue is associated with an increased incidence of cardiovascular and cerebrovascular events in both men’ and women.2 Furthermore, abdominal
obesity is associated with elevated levels of several important risk factors for atherosclerotic disease, such as higher blood pressure, and increased lipid, glucose, and insulin levels.3*4 Abdominal obesity is also associated with a considerably higher incidence of diabetes.’ Although it is possible that the accentuated metabolic risk profile may lead to the increased incidence of atherosclerotic manifestations, other abnormalities may also play an important role. Previous studies have indicated that obesity is associated with an impaired fibrinolytic activity.6‘8 Recent work by Vague et al’ has provided evidence that hyperinsulinemia may be an important reason for the impaired fibrinolytic activity. These investigators found a negative correlation between plasma insulin levels and fibrinolytic activity, possibly due to an increased plasminogen activator inhibitor activity of endothelial cell type (PAI-1). Apart from insulin, the PAI- level also seems to be influenced by other metabolic risk factors, such as the triglyceride levels.’ The pathophysiological importance of elevated PAI- and a low fibrinolytic activity is supported by recent work showing that an elevated PAI- level is associ-
From the Departments of Medicine II, Rehabilitation Medicine. and Surgery, University of GSteborg, Sahlgren’s Hospital, Gothenburg, Sweden. Supported by grants from the Swedish Medical Research Council (project B-3506), Lindgren’s Fund, University of Giiteborg, and Gothenburg Medical Society. Address reprint requests to Ulf Smith, MD. Department of Medicine II, Sahlgren’s Hospital, S-413 45 Gothenburg, Sweden. o 1990 by W.B. Saunders Company. 0026-0495/90/3910-0008$3.00/O
1044
ated with an increased recurrence rate of myocardial infarction.“,” The present study was performed to elucidate whether the impaired fibrinolytic activity in obesity is dependent on the regional distribution of the adipose tissue or on the obesity per se. Therefore, two carefully matched groups of obese women with an abdominal and a gluteofemoral adipose tissue distribution were studied and compared with two groups of nonobese women with the corresponding fat distribution. PATIENTS
Twenty obese, middle-aged women were recruited from the Obesity Outpatient Clinic. Mean duration of obesity, based on individual recall, was 28 * 6 years. All obese women had made several attempts to reduce their body weight. Another 20 nonobese women were recruited by an advertisement in a local newspaper. The patients were selected on the basis of a high or low waist to hip ratio (WHR; 50.8, the median in a female random population in Gothenburg).r Table 1 shows the clinical characteristics of the patients. All patients were healthy and took no medication. The women worked either part- or full-time, and all had a moderate alcohol consumption (mean consumption was 1 L wine per month). Three obese and two lean women were smokers. None of the subjects exercised regularly. METHODS Anthropometric
Studies
Body weight and height were measured with the subjects in underwear and without shoes. Body mass index (BMI) was calculated as body weight (kg) divided by height squared (m*). The waist circumference was measured with a soft tape at the level of the smallest girth above the umbilicus in the standing position. The hip circumference was measured over the widest part of the gluteal region and the WHR calculated. Body composition was calculated from measurements of the naturally occurring 40Kin a whole-body counter (Nuclear Enterprise, Edinburgh, Scotland). Lean body mass was calculated according to Forbes, et al,‘* where 1 kg tissue contains 68.1 mmol potassium. Body fat was calculated by subtracting the lean body mass from the body weight.
Metabolism, Vol39, No 10
(October), 1990: pp
1044- 1048
1045
FIBRINOLYSIS IN OBESITY
Table 1. Body Composition
and Metabolic
Data of Obese and Lean Middle-aged
Women With Different
Obese WHR r 0.8 hl =
WHR z 0.8
WHR < 0.8
101
WHR < 0.8 lot
P Level
+ 3.8
50.2
? 2.5
NS
55.1
* 2.3
56.0
+ 3.1
NS
Body weight (kg)
96.2
+ 3.0
96.4
+ 4.3
NS
69.4
? 7.4
69.3
f 9.5
NS
BMI (kg/m?
36.3
+ 3.3
33.7
f 3.0
NS
25.9
+ 3.4
26.2
f 4.5
NS
Body fat (kg)
46.6
? 2.7
48.1
+ 2.7
NS
25.8
r 8.1
27.9
+ 4.5
NS
LBM (kg)
49.6
+ 1.7
48.3
f 2.0
NS
43.7
r 6.3
41.6
f 5.8
NS
WHR
0.92
+ 0.02
0.74
f 0.01
Obesity Is Associated With an Impaired Fibrinolytic Elevated Plasminogen Activator Inhibitor-l
Kerstin Landin, Lennart Stigendal,
Elsa Eriksson,
Marcin Krotkiewski,
Activity
60 Risberg, Lilian Tengborn,
and
and Ulf Smith
Recent epidemiologic studies have shown that abdominal obesity, characterized by a high waist to hip circumference ratio (WHRL is associated with increased cardiovascular morbidity and mortality. The present study examines components of the fibrinolytic system in obese and lean middle-aged women with a high and low WHR. Ten women in each group were carefully matched with respect to age, body weight, lean body mass, and body fat. Fibrinogen and endothelial type of plasminogen activator inhibitor-l (PAI- j were significantly elevated in the obese women with a high WHR compared with the obese women with a low WHR or with both groups of lean women. In addition, obese women with a high WHR exhibited a greater metabolic risk profile (elevated glucose, insulin, and triglyceride levels). When all subjects were pooled for the analyses, both fibrinogen and PAIlevels correlated positively with glucose and insulin levels. PAI- was also negatively related to degree of insulin sensitivity measured with the euglycemic clamp technique. In the obese groups, WHR but not body mass index (BMI), correlated with PAI- levels. No such correlations were seen in the lean groups. In conclusion, the data show that a high WHR in obese, but not lean middle-aged women, is associated with an impaired fibrinolytic activity. This perturbation becomes enhanced when it is associated with hyperinsulinemia and insulin resistance, which is a typical feature of abdominal obesity. @ 1990 by W. B. Saunders Company.
R
ECENT STUDIES have shown that the distribution of the adipose tissue, in addition
to the amount of body fat, is an important determinant of morbidity and mortality.‘.* Both for lean and obese individuals, relative abdominal preponderance of the adipose tissue is associated with an increased incidence of cardiovascular and cerebrovascular events in both men’ and women.2 Furthermore, abdominal
obesity is associated with elevated levels of several important risk factors for atherosclerotic disease, such as higher blood pressure, and increased lipid, glucose, and insulin levels.3*4 Abdominal obesity is also associated with a considerably higher incidence of diabetes.’ Although it is possible that the accentuated metabolic risk profile may lead to the increased incidence of atherosclerotic manifestations, other abnormalities may also play an important role. Previous studies have indicated that obesity is associated with an impaired fibrinolytic activity.6‘8 Recent work by Vague et al’ has provided evidence that hyperinsulinemia may be an important reason for the impaired fibrinolytic activity. These investigators found a negative correlation between plasma insulin levels and fibrinolytic activity, possibly due to an increased plasminogen activator inhibitor activity of endothelial cell type (PAI-1). Apart from insulin, the PAI- level also seems to be influenced by other metabolic risk factors, such as the triglyceride levels.’ The pathophysiological importance of elevated PAI- and a low fibrinolytic activity is supported by recent work showing that an elevated PAI- level is associ-
From the Departments of Medicine II, Rehabilitation Medicine. and Surgery, University of GSteborg, Sahlgren’s Hospital, Gothenburg, Sweden. Supported by grants from the Swedish Medical Research Council (project B-3506), Lindgren’s Fund, University of Giiteborg, and Gothenburg Medical Society. Address reprint requests to Ulf Smith, MD. Department of Medicine II, Sahlgren’s Hospital, S-413 45 Gothenburg, Sweden. o 1990 by W.B. Saunders Company. 0026-0495/90/3910-0008$3.00/O
1044
ated with an increased recurrence rate of myocardial infarction.“,” The present study was performed to elucidate whether the impaired fibrinolytic activity in obesity is dependent on the regional distribution of the adipose tissue or on the obesity per se. Therefore, two carefully matched groups of obese women with an abdominal and a gluteofemoral adipose tissue distribution were studied and compared with two groups of nonobese women with the corresponding fat distribution. PATIENTS
Twenty obese, middle-aged women were recruited from the Obesity Outpatient Clinic. Mean duration of obesity, based on individual recall, was 28 * 6 years. All obese women had made several attempts to reduce their body weight. Another 20 nonobese women were recruited by an advertisement in a local newspaper. The patients were selected on the basis of a high or low waist to hip ratio (WHR; 50.8, the median in a female random population in Gothenburg).r Table 1 shows the clinical characteristics of the patients. All patients were healthy and took no medication. The women worked either part- or full-time, and all had a moderate alcohol consumption (mean consumption was 1 L wine per month). Three obese and two lean women were smokers. None of the subjects exercised regularly. METHODS Anthropometric
Studies
Body weight and height were measured with the subjects in underwear and without shoes. Body mass index (BMI) was calculated as body weight (kg) divided by height squared (m*). The waist circumference was measured with a soft tape at the level of the smallest girth above the umbilicus in the standing position. The hip circumference was measured over the widest part of the gluteal region and the WHR calculated. Body composition was calculated from measurements of the naturally occurring 40Kin a whole-body counter (Nuclear Enterprise, Edinburgh, Scotland). Lean body mass was calculated according to Forbes, et al,‘* where 1 kg tissue contains 68.1 mmol potassium. Body fat was calculated by subtracting the lean body mass from the body weight.
Metabolism, Vol39, No 10
(October), 1990: pp
1044- 1048
1045
FIBRINOLYSIS IN OBESITY
Table 1. Body Composition
and Metabolic
Data of Obese and Lean Middle-aged
Women With Different
Obese WHR r 0.8 hl =
WHR z 0.8
WHR < 0.8
101
WHR < 0.8 lot
P Level
+ 3.8
50.2
? 2.5
NS
55.1
* 2.3
56.0
+ 3.1
NS
Body weight (kg)
96.2
+ 3.0
96.4
+ 4.3
NS
69.4
? 7.4
69.3
f 9.5
NS
BMI (kg/m?
36.3
+ 3.3
33.7
f 3.0
NS
25.9
+ 3.4
26.2
f 4.5
NS
Body fat (kg)
46.6
? 2.7
48.1
+ 2.7
NS
25.8
r 8.1
27.9
+ 4.5
NS
LBM (kg)
49.6
+ 1.7
48.3
f 2.0
NS
43.7
r 6.3
41.6
f 5.8
NS
WHR
0.92
+ 0.02
0.74
f 0.01
