Contraceptive steroids and coronary artery atherosclerosis in cynomolgus macaques

The influence of two types of steroidal contraception on the extent of coronary, aortic, carotid, and iliaco-femoral atherosclerosis was assessed in 57 cynomolgus macaques with moderate diet-induced hyperlipoproteinemia. Thirteen animals were treated with an intravaginal ring that released 17 beta-estradiol and levonorgestrel. Fifteen females were treated with an oral contraceptive (OC) composed of ethinyl estradiol and norgestrel. Fifteen females received placebo vaginal rings, and 14 males were untreated. The contraceptive treatments resulted in similar large reductions in plasma high-density lipoprotein (HDL) cholesterol concentrations. Neither treatment influenced the prevalence of coronary artery atherosclerosis. However, treatment with the contraceptive vaginal ring was associated with increased extent of coronary artery atherosclerosis (plaque size) relative to untreated females, whereas treatment with the OC was not. The contrasting effects of the two treatments could not be explained by differences in total plasma cholesterol, HDL cholesterol, or blood pressure. The results suggest that the greater estrogenic influence associated with the ethinyl estradiol-containing OC resulted in inhibition of coronary artery atherosclerosis despite a pronounced progestin-induced lowering of plasma HDL cholesterol concentration and, further, that hormonal balance may have a marked influence on the relationship between plasma lipids and atherogenesis.     

Peripheral arterial disease and ankle-brachial pressure index as predictors of mortality in residents of Metlika County, Slovenia

Aim

To test how the presence of peripheral arterial disease predicted mortality of middle-aged and elderly residents of Metlika county, a rural area in southeastern Slovenia.

Methods

In 1987, we interviewed and examined a representative cohort of 646 subjects aged 45-80 years at inclusion without overt coronary or cerebrovascular disease, for cardiovascular risk factors and measured the ankle-brachial pressure index (ABPI). Peripheral arterial disease was defined as ABPI<0.90. The subjects were followed up 15 years or until death. All-cause mortality and cardiovascular mortality were assessed and compared between subjects with and without peripheral arterial disease in a multivariate model.

Results

There were 580 subjects with normal ABPI and 66 subjects with peripheral arterial disease, among which 49 were asymptomatic and 17 had intermittent claudication. Because subjects with peripheral arterial disease were on average 10 years older than those without peripheral arterial disease, the mere presence of peripheral arterial disease was not an independent predictor of mortality. However, there was a significant interaction of peripheral arterial disease with age, with a more pronounced adverse prognostic effect of peripheral arterial disease in younger than in older age groups. For a 55-year-old subject with peripheral arterial disease, the hazard ratio of dying from any cause in the follow-up period was 2.44 (95% confidence interval [CI], 1.15-4.96) in comparison to an age-matched subject without peripheral arterial disease, but at 75 years of age, the hazard ratio decreased to only 0.71 (95% CI, 0.46-1.09). For cardiovascular mortality, the hazard ratio in the presence of peripheral arterial disease was 6.05 (95% CI, 1.87-16.27) at 55 years and 0.92 (95% CI, 0.54-1.52) at 75 years. Among patients with peripheral arterial disease, each decrement of ABPI at inclusion by 0.10 significantly increased the cardiovascular mortality after 15 years by 30% (P = 0.038).

Conclusion

Peripheral arterial disease, even asymptomatic, is an important predictor of adverse cardiovascular prognosis in relatively young patients. Reduced ABPI is a strong, independent predictor of cardiovascular mortality in all patients with peripheral arterial disease.Clinical manifestation of peripheral arterial disease confirmed by reduced ankle-brachial pressure index (ABPI) ranges from the common asymptomatic disease, to the less prevalent intermittent claudication, to the relatively rare critical limb ischemia with rest pain, ulceration or gangrene (1). Even if peripheral arterial disease does not cause typical claudication, it reduces walking speed and walking endurance (2). Regardless of the clinical symptoms, reduced ABPI is a sign of hemodynamic disturbance in the arterial supply of the lower limbs, which is strongly associated with atherosclerosis in the coronary and carotid territories (3). Thus, peripheral arterial disease is associated with increased mortality due to myocardial infarction and ischemic stroke. Several studies described 2-3-fold greater mortality in patients with peripheral arterial disease in comparison with age-matched controls with normal ABPI; patients with peripheral arterial disease had a 5-year mortality of about 30% (4-9). Increasing severity of peripheral arterial disease, expressed as diminishing ABPI, progressively reduces survival (6-9).Most previously studied cohorts were either patients referred for non-invasive vascular testing (6) or patients with known risk factors such as hypertension (8) or hyperlipidemia (4). There is still little data on the prognostic value of largely asymptomatic early-stage peripheral arterial disease in patients free of overt coronary or cerebrovascular disease in a community setting. We have focused on a representative sample of residents of Metlika county, a rural area in southeastern Slovenia to test how the presence of peripheral arterial disease, defined as ABPI<0.90, and the severity of peripheral arterial disease at inclusion, expressed as diminishing ABPI, affected all-cause mortality and cardiovascular mortality in a community setting.     

Antiphospholipid antibodies as a possible risk factor for atherosclerosis in patients with rheumatoid arthritis

Atherosclerosis shares many similarities with inflammatory and autoimmune diseases, among them rheumatoid arthritis (RA). Anticardiolipin antibodies (aCL) and antibodies against beta2-glycoprotein I (anti-beta2GPI) have been detected in sera of RA patients in several studies. We demonstrated aCL and anti-beta2GPI in a selected group of 70 patients with RA (premenopausal women, non-diabetic, non-hypertensive) and compared them with age- and sex-matched controls. There was a significant higher internal carotid artery intima-media thickness and number of plaques in RA patients compared to controls. aCL of IgG and IgM classes were present in 15.7% of RA patients as compared to 5% in the control group. Thirty percent of RA patients had anti-beta2GPI of IgG, IgM and IgA classes compared to 7.5% in controls. Major differences were seen in IgG and IgA classes. Our results support the idea that aCL and anti-beta2GPI represent an important risk factor for atherosclerosis in RA patients. Elevated levels of phosphatidylserine-dependent antiprothrombin antibodies did not contribute significantly to the general prevalence of antiphospholipid antibodies.     

Anatomical basis of the liver hanging maneuver

BACKGROUND/AIMS: The anterior approach to right hepatectomy using the liver hanging maneuver without liver mobilization claims to be anatomically evaluated. During this procedure a 4 to 6-cm blind dissection between the inferior vena cava and the liver is performed. Short subhepatic veins, entering the inferior vena cava could be torn and a hemorrhage, difficult to control, could occur. METHODOLOGY: On 100 corrosive casts of livers the anterior surface of the inferior vena cava was studied to evaluate the position, diameter and draining area of short subhepatic veins and inferior right hepatic vein. The width of the narrowest point on the planned route of blind dissection was determined. RESULTS: The average value of the narrowest point on the planned route of blind dissection was 8.7+/-2.3mm (range 2-15mm). The ideal angle of dissection being 0 degrees was found in 93% of cases. In 7% we found the angle of 5 degrees toward the right border of inferior vena cava to be the better choice. CONCLUSIONS: Our results show that liver hanging maneuver is a safe procedure. With the dissection in the proposed route the risk of disrupting short subhepatic veins is low (7%).     

Traditional and alternative nutrition--levels of homocysteine and lipid parameters in adults

Values of homocysteine and lipid parameters were measured in groups of adults consuming alternative nutrition (vegetarians/lactoovo/, vegans) and compared with a group consuming traditional diet (omnivores, general population). Frequency of hyperhomocysteinemia was 53% in the vegans group, 28% in vegetarians vs. 5% in omnivores. In conditions of lower methionine intake (reduced content in plant proteins), the remethylation pathway of homocysteine metabolism prevails and it is vitamin B12 and folate-dependent. The intake of vitamin B12 is equal to zero in vegans; vegetarians consume 124% of the RDA vs. 383% in omnivores. Serum vitamin levels are significantly lower in subjects consuming alternative nutrition with deficiency observed in 24% of vegetarians, 78% of vegans vs. 0% in omnivores. Serum folate levels are within the reference range in all groups. Mild hyperhomocysteinemia in the groups consuming alternative diet is a consequence of vitamin B12 deficiency. Vegetarians and vegans meet the RDA for energy and fat, and have a favourable proportion of saturated, mono- and polyunsaturated fatty acids on total energy intake; the ratio of linoleic/alpha-linolenic acid in their diet corresponds with the recommendations. They have low cholesterol consumption and higher vitamin E and C intake. Optimal fat intake of correct composition is reflected in lower values of atherosclerosis risk factors (cholesterol, LDL-cholesterol, atherogenic index, saturated fatty acids, triacylglycerols), and significantly higher levels of protective substances (linoleic acid, alpha-linolenic acid, HDL-cholesterol, vitamin E, vitamin E/cholesterol, vitamin C). Low lipid risk factors but higher findings of mild hyperhomocysteinemia in vegetarians mean a diminished protective effect of alternative nutrition in cardiovascular disease prevention.     

Effect of hyperthermic water bath on parameters of cellular immunity

Effects of hyperthermic water bath on selected immune parameters (lymphocyte subpopulations, natural killer (NK) cell counts and their activity) were studied in a group of 10 volunteers. Application of hyperthermic water bath (both topical and whole-body) was followed by a significant reduction of relative B lymphocyte counts. Whole-body hyperthermic water bath reduced relative total T lymphocyte counts, increased relative CD8+ T lymphocyte and NK cell counts and increased NK activity. Whole-body hyperthermic bath increased somatotropic hormone (STH) activity in eight out of 10 volunteers; higher relative counts of CD8+ lymphocytes and NK cells were observed compared with the group of volunteers not responding to hyperthermic water bath by STH secretion. In five volunteers STH was released in response to local hyperthermic water bath and the NK activity of lymphocytes also increased but their relative counts did not. The results suggest that these increases in CD8+ lymphocyte and NK cell counts are probably dependent on increased STH production.