Abdominal obesity is associated with accelerated progression of carotid atherosclerosis in men

Abdominal obesity increases the risk of clinical atherosclerotic diseases, but whether it accelerates the progression of preclinical atherosclerosis is unknown. We studied whether waist-to-hip ratio (WHR) and waist circumference are associated with 4-year increase in indicators of common carotid atherosclerosis, assessed by B-mode ultrasonography, in 774 Finnish men aged 42-60 years without atherosclerotic diseases. Men with WHR of <0.91, 0.91-0.96 and >0.96 (thirds) had increase in maximal intima-media thickness (IMT) of 0.230, 0.255 and 0.281 mm/4 years (P=0.007 for linear trend; P=0.025 for difference) and plaque height of 0.241, 0.254 and 0.291 mm/4 years (P=0.005, P=0.013) adjusting for age, body mass index and technical covariates. Men with waist circumference of <85, 85-93 and >93 cm (thirds) had increase in maximal IMT of 0.227, 0.251 and 0.290 mm/4 years (P=0.011, P=0.035) and plaque height of 0.229, 0.263 and 0.296 mm/4 years (P=0.003, P=0.013). These associations were stronger in men with high (> or =3.8 mmol/l) than lower serum LDL cholesterol (P<0.05 for interaction). This is the first documentation that abdominal obesity is associated with accelerated progression of atherosclerosis, and supports the view that it is an important cardiovascular risk factor. This study emphasizes the role of avoiding abdominal obesity to prevent atherosclerotic diseases.     

Abdominal obesity is associated with increased risk of acute coronary events in men.

AIMS: The purpose of the study was to investigate the associations of abdominal obesity and overall obesity with the risk of acute coronary events. METHODS AND RESULTS: Body mass index indicating overall obesity and waist-to-hip ratio and waist circumference indicating abdominal obesity were measured for 1346 Finnish men aged 42-60 years who had neither cardiovascular disease nor cancer at baseline. There were 123 acute coronary events during an average follow-up of 10.6 years. In Cox regression analyses adjusted for confounding factors, waist-to-hip ratio (P=0.009), waist circumference (P=0.010) and body mass index (P=0.013) as continuous variables were associated directly with the risk of coronary events. These associations were in part explained by blood pressure, diabetes, fasting serum insulin, serum lipids, plasma fibrinogen, and serum uric acid. Waist-to-hip ratio of > or =0.91 was associated with a nearly threefold risk of coronary events. Waist-to-hip ratio provided additional information beyond body mass index in predicting coronary heart disease, whereas body mass index did not add to the predictive value of waist-to-hip ratio. Abdominal obesity combined with smoking and poor cardiorespiratory fitness increased the risk of coronary events 5.5 and 5.1 times, respectively. CONCLUSIONS: Abdominal obesity is an independent risk factor for coronary heart disease in middle-aged men and even more important than overall obesity. Since the effect of abdominal obesity was strongest in smoking and unfit men, the strategy for lifestyle modification to prevent coronary heart disease should address these issues jointly.     

Abdominal obesity is associated with an impaired fibrinolytic activity and elevated plasminogen activator inhibitor-1

Recent epidemiologic studies have shown that abdominal obesity, characterized by a high waist to hip circumference ratio (WHR), 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 -1 (PAI-1) 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 PAI-1 levels correlated positively with glucose and insulin levels. PAI-1 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-1 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.     

Excess mortality associated with diuretic therapy in diabetes mellitus.

OBJECTIVE. To determine whether the high mortality among diabetic patients receiving treatment for hypertension can be explained by associated risk factors or must be attributed to a deleterious effect of antihypertensive treatment. DESIGN. Cohort analytic study with a median follow-up of 4.5 years. SETTING. Outpatients with diabetes and severe retinopathy who were enrolled in a multicenter, randomized clinical trial of laser treatment to prevent blindness had ophthalmologic examinations every 4 months and annual medical examinations that included measurement of blood pressure and recording of anti-hypertensive treatment. Only 5.5% of the patients were unavailable for follow-up. When a patient died, the circumstances surrounding the death were reviewed and classified by a mortality review committee. PARTICIPANTS.--There were 759 participants in the study; they were white, were aged 35 to 69 years, and had normal serum creatinine levels at the baseline examination. MEASUREMENTS AND MAIN RESULTS.--Patients were classified into five groups according to information recorded at the baseline and first annual follow-up examinations: normotensive (diastolic blood pressure less than 90 mm Hg), untreated hypertensive, hypertensive treated by diuretics alone, hypertensive treated by other agents alone, and hypertensive treated by both agents. Cardiovascular mortality was higher in patients treated for hypertension than in patients with untreated hypertension. The excess was primarily found in patients treated with diuretics alone, although that group had the lowest blood pressure with treatment. After adjusting for differences in risk factors, cardiovascular mortality was 3.8 times higher in patients treated with diuretics alone than in patients with untreated hypertension (P less than .001). CONCLUSIONS.--In individuals with diabetes, intervention with diuretics to reduce hypertension is associated with excess mortality. Until there is a clinical trial showing a beneficial effect of diuretic treatment in diabetic patients, there is urgent need to reconsider its continued usage in this population.     

Antihypertensive therapy and its effects on potassium homeostasis

The role of potassium in cardiovascular disease and the importance of preserving potassium balance have emerged as clinical hot points, particularly as they relate to cardioprotective and renoprotective therapies that secondarily promote potassium retention. Antihypertensive medications that most commonly influence serum potassium levels and/or total body potassium include beta blockers and potassium-wasting and potassium-sparing diuretics as well as angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. Uncertainty exists as to the best way to monitor potassium levels when any of these drug therapies are used, particularly in the setting of chronic kidney disease and/or heart failure. Guidelines for the monitoring of serum potassium levels in the setting of antihypertensive therapy are at best makeshift and often drawn from the know-how of the treating physician.     

Growth hormone replacement therapy is not associated with retinal changes

GH and/or growth factors are thought to play a role in the pathogenesis of diabetic retinopathy. In addition, the occurence of retinal changes mimicking diabetic retinopathy in two GH-deficient (GHD) patients receiving GH replacement therapy (GHRT) has recently been reported. The present study was performed to evaluate whether this was a coincidence or whether GHRT might regularly induce retinal changes. Sixty-one GHD patients on GHRT with a mean age of 42.5 +/-17.3 yr were examined by one ophthalmologist (AR). The mean duration of GHRT was 8.4 +/- 3.7 yr in childhood onset and 3.5 +/- 2.1yr in adult onset patients. Plasma insulin-like growth factor I concentrations were 76.4 +/- 49.6 ng/mL before GHRT and 244.3 +/- 119.2 ng/mL while receiving GHRT with a dose of 1.7 +/- 0.7 IU/day. After pupil dilatation with tropicamide, fundus examinations of both eyes were performed using a Volk 90 diopter fundus lens with a slit lamp (Haag Streit, Bern, Switzerland). In none of the patients were vascular or retinal changes like macular edema, microaneurysms, hemorrhages, hard exsudates, cotton wool spots, preproliferative signs, or proliferations found. The optic discs were also normal in all patients. We conclude, therefore, that long-term GHRT can be administered safely in GHD patients without an increased risk of retinal changes.     

Birth weight is nongenetically associated with glucose intolerance in elderly twins, independent of adult obesity

OBJECTIVES: Using a unique twin approach, we examined the extent to which birth weight is determined by genetic and nongenetic factors and whether associations between birth weight and measures of glucose metabolism are of genetic or nongenetic origin. SETTING/SUBJECTS: An oral glucose tolerance test (OGTT) was performed in a population-based cohort of twins including 138 same-sex monozygotic (MZ) and 214 dizygotic (DZ) twin pairs aged 55-73 years whose birth weight was known. Heritability of birth weight was determined and regression analyses with intra-twin pair differences of birth weight and measures of glucose metabolism, with and without adjustment for adult obesity, were performed. RESULTS: The heritability of birth weight was estimated to be 38%. We demonstrated significant nongenetic associations between birth weight and measures of glucose homeostasis in MZ twins, with a reduction in fasting plasma glucose, 120 min post-OGTT plasma glucose, fasting plasma insulin and HOMA-IR index of 15.7%, 25.5%, 26.4% and 37.2%, respectively, for every 1 kg increase in birth weight. The nongenetic negative associations between birth weight and measures of glucose intolerance were independent of adult obesity, whereas the nongenetic association between birth weight and insulin resistance persisted, although not as strongly, after adjusting for current body size. CONCLUSIONS: We demonstrated a genetic component to birth weight in elderly twins. When adjusting for this influence, we found a nongenetic negative association between birth weight and glucose tolerance as well as insulin resistance that was partially independent of adult obesity. This implies that the foetal environment influences glucose homeostasis in elderly twins.