Effect of external sleep disturbance on sleep architecture in perimenopausal and postmenopausal women.

OBJECTIVE: This study aimed to use external sleep disturbance as a model to evaluate sleep architecture in climacteric women before and after menopausal hormone therapy (MHT). METHODS: Seventeen perimenopausal and 18 postmenopausal women underwent a polysomnography protocol: an adaptation night, a reference night and a sleep disturbance night with one hand loosely tied to the bed for blood sampling. The sleep architecture of the reference and disturbance nights were compared. The 24-h urinary free cortisol concentration (UFC) was measured. The procedure was repeated after 6 months on MHT or placebo. RESULTS: Fifteen perimenopausal and 17 postmenopausal women completed the study. The perimenopausal and postmenopausal groups were combined. During external sleep disturbance, sleep was shorter and more fragmented; with less stage 2, slow-wave and rapid eye movement (REM) sleep and more wake time and awakenings, both at baseline and after the treatment period. Compared to the placebo group, sleep disturbance was minor for women on MHT: sleep was not shortened and the amount of slow-wave sleep did not decrease. Increased 24-h UFC was observed only during MHT. CONCLUSIONS: Sleep in climacteric women is easily disturbed, leading to shorter and more fragmented sleep with less deep sleep and REM sleep. Six months of MHT attenuates the observed sleep disturbance.

Maternal depressive symptoms during pregnancy, placental expression of genes regulating glucocorticoid and serotonin function and infant regulatory behaviors.

BACKGROUND: Glucocorticoids and serotonin may mediate the link between maternal environment, fetal brain development and 'programming' of offspring behaviors. The placenta regulates fetal exposure to maternal hormonal signals in animal studies, but few data address this in humans. We measured prospectively maternal depressive symptoms during pregnancy and mRNAs encoding key gene products determining glucocorticoid and serotonin function in term human placenta and explored associations with infant regulatory behaviors. METHOD: Bi-weekly self-ratings of the Center for Epidemiologic Studies Depression Scale from 12th to 13th gestational week onwards and term placental mRNAs of 11beta-hydroxysteroid dehydrogenase type 2 (HSD2B11), type 1 (HSD1B11), glucocorticoid (NR3C1), mineralocorticoid receptors (NR3C2) and serotonin transporter (SLC6A4) were obtained from 54 healthy mothers aged 32.2 ± 5.3 years with singleton pregnancies and without pregnancy complications. Infant regulatory behaviors (crying, feeding, spitting, elimination, sleeping and predictability) were mother-rated at 15.6 ± 4.2 days. RESULTS: Higher placental mRNA levels of HSD2B11 [0.41 standard deviation (s.d.) unit increase per s.d. unit increase; 95% confidence interval (CI) 0.13-0.69, p = 0.005], HSD1B11 (0.30, 0.03-0.57, p = 0.03), NR3C1 (0.44, 0.19-0.68, p = 0.001) and SLC6A4 (0.26, 0.00-0.53, p = 0.05) were associated with more regulatory behavioral challenges of the infant. Higher placental NR3C1 mRNA partly mediated the association between maternal depressive symptoms during pregnancy and infant regulatory behaviors (p < 0.05). CONCLUSIONS: Higher placental expression of genes regulating feto-placental glucocorticoid and serotonin exposure is characteristic of infants with more regulatory behavioral challenges. Maternal depression acts, at least partly, via altering glucocorticoid action in the placenta to impact on offspring regulatory behaviors.

Maternal depressive symptoms throughout pregnancy are associated with increased placental glucocorticoid sensitivity.

BACKGROUND: Maternal prenatal depression predicts post-partum depression and increases risk of prematurity and low birth weight. These effects may be mediated by altered placental function. We hypothesized that placental function would be influenced by the gestational week of experiencing depressive symptoms and aimed to examine associations between maternal depressive symptoms during pregnancy and placental expression of genes involved in glucocorticoid and serotonin transfer between mother and fetus. METHOD: We studied women participating in a prospective pregnancy cohort: the Prediction and Prevention of Preeclampsia (PREDO) Study, Helsinki, Finland. Maternal depressive symptoms were assessed at 2-week intervals throughout pregnancy in 56 healthy women with singleton, term pregnancies. Messenger ribonucleic acid (mRNA) levels of glucocorticoid (GR) and mineralocorticoid (MR) receptors and serotonin transporter (SLC6A4), 11ß-hydroxysteroid dehydrogenase type 1 (HSD1) and 2 (HSD2) were quantified in placental biopsies. RESULTS: In adjusted analyses women who reported higher depressive symptoms across the whole pregnancy had higher mRNA levels of GR [effect size 0.31 s.d. units, 95% confidence interval (CI) 0.01-0.60, p = 0.042] and MR (effect size 0.34 s.d. units, 95% CI 0.01-0.68, p = 0.047). These effects were significant for symptoms experienced in the third trimester of pregnancy for GR; findings for MR were also significant for symptoms experienced in the second trimester. GR and MR mRNA levels increased linearly by having the trimester-specific depressive symptoms scores 0, 1 or 2-3 times above the clinical cut-off for depression (p = 0.003, p = 0.049, respectively, and p = 0.004, p = 0.15 in adjusted analyses). CONCLUSIONS: Our findings offer potential gestational-age-specific mechanisms linking maternal depressive symptoms during pregnancy via placental biology. Future studies will test whether these also link with adverse offspring outcomes.

Multiple sclerosis and vitamin D during pregnancy and lactation.

BACKGROUND: Both pregnancy and high vitamin D concentration seem to generate a protective environment against multiple sclerosis (MS) relapses. Longitudinal case-control analysis of vitamin D concentrations during pregnancy and lactation of MS mothers is lacking. AIMS OF THE STUDY: To examine serum 25-hydroxyvitamin-D3 levels of MS patients during and after pregnancy and compare these to the levels measured in healthy controls. METHODS: Fifteen relapsing-remitting MS mothers underwent repeated testing for 25-hydroxyvitamin-D3 at 10-12, 26-28 and 35-37 gestational weeks and 1, 3 and 6 months post-partum. An identical series of samples was collected from six control mothers. RESULTS: The prevalence of vitamin D deficiency (<50 nmol/l) during pregnancy was high (73%) among MS patients. Vitamin D levels were significantly higher during pregnancy when compared to early post-partum values among MS patients. At the end of the follow-up period, the vitamin D levels returned to levels observed in early pregnancy. In healthy controls, the alterations during and after pregnancy were similar in nature, but the vitamin D concentrations were higher at all time points when compared to MS patients (P = 0.037). CONCLUSIONS: Vitamin D deficiency during the pregnancy and lactation seems to be common in mothers with MS and needs to be treated adequately.

Aspirin in the prevention of pre-eclampsia in high-risk women: a randomised placebo-controlled PREDO Trial and a meta-analysis of randomised trials.

OBJECTIVE: To study the effect of aspirin in the prevention of pre-eclampsia in high-risk women. DESIGN: Randomised, double-blinded, placebo-controlled trial. SETTING: Maternity clinics in ten Finnish hospitals participating in the PREDO Project. SAMPLE: A total of 152 women with risk factors for pre-eclampsia and abnormal uterine artery Doppler velocimetry. METHODS: Participants were randomised to start either aspirin 100 mg/day or placebo at 12 + 0 to 13 + 6 weeks + days of gestation. Because of the limited power of this trial, we also conducted a meta-analysis of randomised controlled trials that included data on 346 women with abnormal uterine artery Doppler flow velocimetry, and aspirin 50-150 mg/day started at or before 16( ) weeks of gestation. MAIN OUTCOME MEASURE: Pre-eclampsia, gestational hypertension and birthweight standard deviation (SD) score. Outcome measures for the meta-analysis were pre-eclampsia, severe pre-eclampsia, preterm (diagnosed <37 + 0 weeks of gestation) and term pre-eclampsia. RESULTS: From the 152 randomised women, 121 were included in the final analysis. Low-dose aspirin did not reduce the rate of pre-eclampsia (relative risk [RR] 0.7, 95% CI 0.3-1.7); gestational hypertension (RR 1.6, 95% CI 0.6-4.2); early-onset pre-eclampsia (diagnosed <34 + 0 weeks of gestation) (RR 0.2, 95% CI 0.03-2.1); or severe pre-eclampsia (RR 0.4, 95% CI 0.1-1.3); and the results were not statistically significant in an intention-to-treat analysis. However, our meta-analysis, including the current data, suggested that low-dose aspirin initiated before 16 weeks of gestation reduces the risk of pre-eclampsia (RR 0.6, 95% CI 0.4-0.8) and severe pre-eclampsia (RR 0.3, 95% CI 0.1-0.7). CONCLUSIONS: Our trial showed no statistically significant effect of aspirin in preventing pre-eclampsia in high-risk women. However, our meta-analysis suggested that aspirin may reduce the incidence of pre-eclampsia.

Vacuum assistance therapy as compared to early reconstructive treatment in deep sternal wound infection.

BACKGROUND AND AIMS: Deep sternal wound infection is a major concern after cardiac surgery. This study describes the incidence of postoperative deep sternal wound infections after cardiac surgery and compares two available treatment modalities. MATERIALS AND METHODS: In Tampere University Hospital, 7973 open heart operations were performed between 2007 and 2016. Patients treated for a postoperative deep sternal wound infection were categorized in two groups based on treatment: revision surgery with early reconstruction (revision group; 74 patients) or vacuum-assisted closure treatment (VAC group; 55 patients). The end points in comparisons were overall mortality and hospitalization time. RESULTS: A total of 129 patients (1.6%) developed a postoperative deep sternal wound infection. The 30-day mortality rates were 8.1% and 3.6%, the 90-day mortality rates were 15.5% and 18.2%, and the 1-year mortality rates were 17.6% and 23.6% for the revision and VAC group, respectively. There was no statistically significant difference in mortality rates. The hospital stay was 18 days in the revision group and 38 days in the VAC group (p < 0.001). The secondary intensive care unit stay was longer in the VAC group (median 1 vs 4, p = 0.011). The most common pathogens isolated in the first reoperation were coagulase-negative staphylococci (33.8% and 41.8%, respectively; p = 0.366), and positive candida findings were more common in the VAC group (4.1% vs 37.0 %, p < 0.001). CONCLUSION: Vacuum-assisted closure treatment induces an inferior outcome in terms of fungal infections, treatment times, and the number of reoperations.

Genetic association study of endothelin-1 and its receptors EDNRA and EDNRB in migraine with aura.

The effect of endothelin-1 and its receptors EDNRA and EDNRB in migraine with aura (MA) susceptibility is not established yet. We studied the association between the MA end-diagnosis and three migraine trait components and 32 single nucleotide polymorphisms (SNPs) capturing the variation of endothelin genes in 850 Finnish migraine patients and 890 non-migrainous individuals. The SNPs showing evidence of association were further studied in 648 German migraine patients and 651 non-migrainous individuals. No significant association was detected. However, the homozygous minor genotype (5% in cases) of the EDNRA SNP rs2048894 showed nominal association with MA both in the Finnish sample (P = 0.015) and in the pooled sample [odds ratio (OR) 1.61, 95% confidence interval (CI) 1.12-2.32, P = 0.010] when adjusted for gender and sample origin. The trait age of onset < 20 years was also associated with rs2048894 (OR 1.69, 95% CI 1.13-2.54, P = 0.011) in the pooled sample. To confirm this finding studies on even larger samples are required.

Recombinant human type II collagen as a material for cartilage tissue engineering.

PURPOSE: Collagen type II is the major component of cartilage and would be an optimal scaffold material for reconstruction of injured cartilage tissue. In this study, the feasibility of recombinant human type II collagen gel as a 3-dimensional culture system for bovine chondrocytes was evaluated in vitro. METHODS: Bovine chondrocytes (4x106 cells) were seeded within collagen gels and cultivated for up to 4 weeks. The gels were investigated with confocal microscopy, histology, and biochemical assays. RESULTS: Confocal microscopy revealed that the cells maintained their viability during the entire cultivation period. The chondrocytes were evenly distributed inside the gels, and the number of cells and the amount of the extracellular matrix increased during cultivation. The chondrocytes maintained their round phenotype during the 4-week cultivation period. The glycosaminoglycan levels of the tissue increased during the experiment. The relative levels of aggrecan and type II collagen mRNA measured with realtime polymerase chain reaction (PCR) showed an increase at 1 week. CONCLUSION: Our results imply that recombinant human type II collagen is a promising biomaterial for cartilage tissue engineering, allowing homogeneous distribution in the gel and biosynthesis of extracellular matrix components.

The effect of cross-linking time on a porous freeze-dried collagen scaffold using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide as a cross-linker.

Collagen is a widely studied natural polymer for use as a scaffold material for various tissue engineering applications. Untreated collagen, however, has a fast biodegradation rate and low mechanical strength. Additionally, collagen cross-linking has been studied extensively and different cross-linking agents and methods have been explored. Although glutaraldehyde (GA) is the most convenient and traditional chemical agent currently used for this purpose, it nevertheless poses potential cytotoxicity. Therefore, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) is widely being studied as well, due to its characteristic of being a zero-length cross-linker that does not remain in the collagen's structure. Nevertheless, cross-linking with EDC can be implemented in several ways. In this study, two methods of cross-linking with EDC, prior to and post freeze-drying, were examined for freezedried collagen scaffolds. Four different collagen concentrations between 0.3 and 2.0 w% were inspected and different cross-linking methods were examined by a differential scanning calorimeter (DSC) to determine the collagen's denaturation temperature (Td). Furthermore, the water uptake abilities of the scaffolds were tested in phosphate buffered saline (PBS) and the scaffolds' pore structure was examined with a scanning electron microscope (SEM). As assumed, the DSC measurements demonstrated that collagen Td values increased with increasing collagen concentration. With lower collagen concentrations, the cross-linking post freeze-drying enhanced the Td values, but with higher collagen concentrations, the Td values were increased only with cross-linking prior to freeze-drying. The water uptake measurement showed increased water uptake ability when cross-linking post freezedrying. The pore sizes of the different collagen scaffolds were between 50 and 120 mum.

No association of migraine to the GABA-A receptor complex on chromosome 15.

To date, no gene variants predisposing to common forms of migraine have been convincingly identified. Recently, significant linkage to a cluster of gamma-amino butyric acid (GABA)-A receptors on Chr 15q11-q13 was reported. We performed an extensive association study using 898 MA cases and 900 matched controls by covering the same gene cluster with 34 single nucleotide polymorphisms (SNPs). No association to MA was detected, suggesting that common variants of the GABA cluster are unlikely to be major contributors of MA susceptibility.

The effect of low-dose aspirin on serum placental growth factor levels in a high-risk PREDO cohort.

OBJECTIVES: Our first aim was to study the longitudinal changes of serum placental growth factor (PlGF) concentration between 12+0 and 28+0 weeks of gestation in the prospective PREDO cohort. Our second aim was to study the effect of low-dose acetylsalicylic acid (LDA; 100 mg/day), started before the 14th week of gestation, on PlGF concentration. STUDY DESIGN: Blood samples were collected at 12+0-14+0, 18+0-20+0 and 26+0-28+0 weeks of gestation in 101 women without and 309 with clinical risk factors for pre-eclampsia. Risk-women were divided into two groups: to those who had medium risk for pre-eclampsia and to those who had high risk for pre-eclampsia. Finally there were seven groups according to risk, treatment (no prevention/placebo/LDA) and outcome measure pre-eclampsia. Longitudinal changes in the PlGF concentration between groups were compared. To investigate the effect of LDA on serum PlGF concentration, placebo (N = 62) and LDA (N = 61) groups were compared. A repeated measures ANOVA was used to analyze differences in PlGF levels between the groups. RESULTS: The increase in serum PlGF concentration was higher in LDA than in placebo group (time × group effect, p = 0.046). The increase in serum PlGF concentration during pregnancy was lower in high-risk women who had placebo and developed pre-eclampsia and in medium-risk women who developed pre-eclampsia compared to the other women (time × group effect, p < 0.001). There were no differences in PlGF change between low-risk women, medium-risk women who did not develop pre-eclampsia, high-risk women in the placebo group without pre-eclampsia and high-risk women in the LDA group with and without pre-eclampsia (p = 0.15). CONCLUSIONS: Our finding suggests an association between LDA started before 14 weeks of gestation and higher increase in serum PlGF concentration.

Estrogen metabolism and excretion in Oriental and Caucasian women.

BACKGROUND: Caucasian and Oriental women have different incidence rates of breast cancer. Among the underlying risk factors for the development of breast cancer in the women of these two groups may be their different diets and patterns of estrogen metabolism and excretion. The absolute levels and relative ratios of 16 alpha-hydroxylated estrogens and 2-hydroxylated estrogens (catechol estrogens) in the body may have a role in the etiology of breast cancer, but studies so far have provided only conflicting results. PURPOSE: Our goal was to study estrogen metabolism, in particular, the extent of 2-hydroxylation and 16 alpha-hydroxylation of estrogens in two groups of women, one Caucasian and one Oriental, with inherently different breast cancer risks. METHODS: Dietary records were analyzed over 3-day periods in the mid-follicular phase, twice, at 6-month intervals for 13 premenopausal Oriental women, recent immigrant arrivals in Hawaii with presumed low risk of breast cancer, and for 12 premenopausal Finnish women with presumed higher risk. The urinary estrogen profile was measured by gas chromatography-mass spectrometry and plasma and fecal estrogens were assayed by chromatographic radioimmunoassays. RESULTS: Mean fat intake per 1000 kcal was 73% higher (P < .001) in the Finnish women, but the mean fiber intake and fecal weights were similar to those of the Oriental women. Compared with Oriental women, Finnish women had 46% higher plasma estradiol (P < .01) and 124% higher plasma estrone sulfate (P < .01); however, after adjustment for differences in age and body mass index, only the difference in estrone sulfate remained statistically significant (P < .05). Mean plasma levels of estrone and estradiol correlated with height after adjustment for body mass index (P < .05). Mean plasma levels of estrone and sex hormone-binding globulin were similar. The Finns had higher mean urinary estrone (193%), estradiol (166%), various catechol estrogens (130%-439%), and total estrogen excretion (123%) (all P < .001), but similar 16 alpha-hydroxylated estrogen excretion. As calculated, 16 alpha-hydroxylation of estrone was significantly increased (P < .01) in the Oriental women, but 2-hydroxylation, 4-hydroxylation, and 16 beta-hydroxylation of estrone were similar in both groups. The ratio of catechol estrogen to 16 alpha-hydroxylated estrogen was four to five times higher (P < .001) in the Finnish women. The Oriental women had two to three times higher fecal excretion of estrogens than the Finnish women (P < .01). CONCLUSIONS: Our results indicate that high catechol estrogen formation may be a greater risk factor for breast cancer than high 16 alpha-hydroxylation of estrogens. However, the main risk factor for the Finnish women, as opposed to the Oriental women, may be their higher estrogen levels that result from a higher fat diet, higher estrogen production related to their greater height, and lower fecal estrogen excretion.

Quantification of Pro alpha 1(I) collagen mRNA in skin biopsy specimens: levels of transcription in normal skin and in granuloma annulare.

The synthesis of type I collagen, the major component of the skin, is known to be modulated in aging and in various skin diseases and treatments. In vivo analysis of type I collagen expression, however, is difficult because of the low cell density of the dermis and the small amount of RNA obtainable from skin biopsy specimens. We present here a quantitative polymerase chain reaction method for the quantification of pro alpha 1(I) collagen mRNA in skin punch biopsy specimens. The targeted mRNA and a synthetic RNA as an internal standard were co-amplified together with the same primers. Collagen synthesis was found to decline after birth, so that the amount of pro alpha 1(I) collagen mRNA in the skin of 5- to 58-y-old donors was 17-37% of that in fetal skin. Slot-blot hybridization also indicated that the amount of pro alpha 1(I) collagen mRNA was much lower in adult skin than in fetal skin. In samples from lesional skin of two granuloma annulare patients, the number of pro alpha 1(I) mRNA molecules was increased 4- or 5-fold compared with values from nonlesional skin of the same patients. The method presented is a highly sensitive polymerase chain reaction application, requiring only very small amounts of total RNA.

Urinary excretion of lignans and isoflavonoid phytoestrogens in Japanese men and women consuming a traditional Japanese diet.

Epidemiologic studies revealed low mortality in hormone-dependent cancer in Japanese women and men consuming a traditional diet. We previously found that certain diphenolic food components, lignans and isoflavonoids, which are converted to biologically active hormone-like substances by intestinal microflora, may be cancer-protective agents. Therefore, we studied urinary excretion of these compounds (enterolactone, enterodiol, daidzein, equol, and O-desmethylangolensin) in 10 women and 9 men in a rural village south of Kyoto, Japan. The subjects consumed a typical low-fat diet with much rice and soy products, fish, and vegetables. An isotope-dilution gas chromatographic-mass spectrometric method was used for the assays. The urinary excretion of lignans was low but that of the isoflavonoids was very high. The excretion of isoflavonoids correlated with soybean-product intake. The low mortality in breast and prostate cancer of Japanese women and men, respectively, may be due to the high intake of soybean products.

Diet and plasma androgens in postmenopausal vegetarian and omnivorous women and postmenopausal women with breast cancer.

We studied 27 postmenopausal women, 9 vegetarians, 10 omnivores, and 8 apparently healthy women with breast cancer (BC), four times during 1 y. Dietary intakes were recorded and plasma androgens and sex-hormone-binding globulin (SHBG) binding capacity were determined. Androstenedione (A), testosterone (T), free T (FT), and SHBG were higher in omnivores than in vegetarians. In multiple correlation analysis, intakes of protein and fat were positively correlated with A, T, and FT, whereas the intakes of carbohydrate, grain, total fiber, and grain fiber showed the opposite correlations. Protein intake was positively correlated with percentage FT (%FT) and negatively with SHBG. BC patients had a similar pattern to omnivores with even higher levels of A and T (significant compared with vegetarians) and they showed significantly higher FT and lower SHBG than both control groups. We conclude that a Western-type diet in postmenopausal women is associated with high A, T, %FT, FT, and low SHBG and this pattern was apparent in the BC patients.

Significance of skeletal muscle properties on fitness, long-term physical training and serum lipids.

The percentage of slow-twitch (ST) fibers in a person's skeletal muscle, e.g. muscle fiber composition (ST-%), may have a significant impact on physical activity, fitness level, serum high density lipoprotein cholesterol (HDL-C) concentration, and ultimately, on the risk of coronary heart disease (CHD). We studied the effect of a 12 month home-based exercise training program on skeletal muscle metabolic activity, serum lipids, and hormones in 12 healthy middle-aged men (sedentary men) with a low level of fitness and leisure-time physical activity (LTPA). Their parameters and changes in them were compared with 12 men of the same age with defined CHD and with two groups (15 each) of physically active men, who had either a high ST-% (high-ST-men) or a low ST-% (low-ST-men). In the sedentary men, CHD-patients and low-ST-men, the mean ST-% (42, 44, and 49%, respectively) was similar but was significantly higher in the high-ST-men (73%). The sedentary men whose LTPA mean was 34 and 19% of the mean of low-ST-men (mean of 2137 kcal/week) and high-ST-men (mean of 3845 kcal/week), respectively, increased their LTPA from a mean of 728-1526 kcal/week (P < 0.01). After training, we found an increase in serum HDL-C by 21%, (P < 0.01) and apo A-I by 36% (P < 0.01), and a decrease in serum LDL-C by 8%. The cholesterol/HDL-C ratio decreased by 17(% (P < 0.01) and the LDL-C/HDL-C ratio decreased by 22% (P < 0.01). Skeletal muscle lipoprotein lipase (LPL) activity increased by 65% (P < 0.001). Moreover, the increase in LPL as well as in HDL-C concentration tended to be more pronounced the higher the level was before training. The oxidative enzyme activity of alpha-ketoglutarate dehydrogenase (KGDH) in skeletal muscle and the activity of carnitine palmitoyltransferase (CPT) in lipid metabolism increased, whereas glycolytic phosphofructokinase (PFK) did not change but the PFK to CPT ratio decreased, which was reflected as a decrease of lactate accumulation during exercise. Increase in CPT activity correlated significantly (r(s) = 0.81, P < 0.01) with the increase in HDL-C concentration. In all men (n = 54), the CPT activity correlated negatively with serum triglyceride concentration (r(s) = -0.34, P < 0.05) but positively with serum HDL-C concentration and ST-% (r(s) = 0.34, P < 0.05 and r(s) = 0.47, P < 0.01, respectively). In all healthy men, (n = 42) LTPA correlated with both Vo2max, and ST-% (r(s) = 0.76, P < 0.001 and r(s) = 0.54, P < 0.001, respectively) and with serum HDL-C and apo A-I concentrations (r(s) = 0.35, P < 0.05 and r(s) = 0.54, P < 0.001, respectively). Serum sex hormones did not show significant associations with serum lipids, but in sedentary men, serum total and free testosterone as well as the ratio of free testosterone to free estradiol decreased significantly after training. These findings confirm the pronounced effects of a home-based exercise training program on CHD risk factors and they underline the importance of considering skeletal muscle properties when studying serum lipids and lipoproteins and their modifications in the field of health-related fitness and physical activity.

Serum lipoproteins, sex hormones and sex hormone binding globulin in middle-aged men of different physical fitness and risk of coronary heart disease.

Serum concentrations of lipoproteins, apolipoprotein A-I (Apo A-I), androgens, including biologically active free testosterone (free T), and sex hormone binding globulin (SHBG) and their associations were studied in 3 groups of men of different physical fitness and risk of CHD, consisting of male CHD patients, joggers and healthy controls. Of the 3 study groups, men with angiographically assessed CHD had the lowest HDL-C (P less than 0.002) and highest LDL-C and triglyceride (TG) levels (P = 0.05 and P less than 0.001) and lower 5 alpha-dihydrotestosterone (5 alpha-DHT) levels than joggers (P less than 0.02). Joggers had the highest serum high density lipoprotein cholesterol (HDL-C), Apo A-I and SHBG levels and lowest serum low density lipoprotein cholesterol (LDL-C) compared to the other groups (P less than 0.01). In correlation analysis 5 alpha-DHT was the most significant positive determinant of HDL-C and Apo A-I levels in CHD patients (r = 0.56 and r = 0.55, respectively, P less than 0.05). Moreover, SHBG was significantly positively correlated to both HDL-C and Apo A-I levels in patients, in the whole study group and in healthy men separately (r = 0.37-0.52, P less than 0.01). These significant correlations were also confirmed when age variation and differences in body mass index and smoking were controlled in multivariate analysis and in addition, in multivariate analysis both serum free and total testosterone were inversely related to serum triglyceride (TG) levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Associations between skeletal muscle properties, physical fitness, physical activity and coronary heart disease risk factors in men.

High physical fitness and physical activity are associated with favourable lipid levels, especially a high level of high density lipoprotein cholesterol (HDL-C). A person's skeletal muscle properties, metabolism and percentage of different muscle fibres (ST-%), which may modify coronary heart disease (CHD) risk factors, such as serum insulin, obesity and serum sex hormones may also influence his fitness level and leisure-time physical activity. We studied the associations of physical fitness, physical activity and ST-% with serum lipids and lipoproteins in 72 healthy men. Their parameters were compared with those of 20 men with defined CHD. Significant interrelationships between ST-%, fitness and leisure-time physical activity index (LTPAI) were observed. Multiple regression analysis showed that ST-%, fitness and leisure-time physical activity explained about 32% of the variation in HDL-C in the healthy men. In healthy men ST-% correlated positively with fitness (r(s) = 0.62, P < 0.001) and with LTPAI (r(s) = 0.62, P < 0.001). Fitness level also correlated significantly with LTPAI (r(s) = 0.81, P < 0.001). Serum insulin showed negative associations with ST-% (r(s) = -0.63, P < 0.001) and fitness (r(s) = -0.54, P < 0.001) and LTPAI (r(s) = -0.62, P < 0.001). Free fraction of testosterone correlated negatively with serum HDL-C level (r(s) = -0.34, P < 0.01), with fitness (r(s) = -0.41, P < 0.001) and with LTPAI (r(s) = -0.54, P < 0.001). In sedentary men with the lowest fitness and physical activity the mean of ST-% (45%) was similar to that in CHD patients (44%). However, ST-% in men in the highest tertile of physical activity and fitness (68%) was significantly higher than in CHD patients and in men in the lowest tertile of physical activity and fitness. Skeletal muscle enzyme activity in lipid metabolism was significantly lower in both CHD patients and in sedentary and low-fit men than that in fitter and physically active men. The present data imply that skeletal muscle properties are important determinants of risk profiles, such as physical activity, fitness and serum lipid and lipoprotein patterns. Although fitness is a graded, independent predictor of mortality from CHD, a relatively high fitness level is not enough. This was clearly observed in the clustering analysis, in which the healthy men, according to their ST-%, fitness, leisure-time physical activity and serum sex hormone binding globulin (SHBG), fell into three natural groups: (i) Inactive men with lowest ST-% (mean 42%), lowest fitness (10.7 METs) and lowest HDL-C (1.36 mm/l); (ii) Fit men with high ST-% (66%), high fitness (14.5 METs) and moderately high HDL-C (1.54 mol/l); (iii) Active men with high ST-% (66%), highest fitness (14.9 METs) and highest serum HDL (1.83 mmol/l). The results support the idea that both fitness and physical activity give further protection against CHD by modifying risk factors. Our findings also suggest that skeletal muscle properties should be considered in the studies which assess CHD risk factors and their modifications especially in the field of health-related fitness.

Relationship of skeletal muscle fiber type to serum high density lipoprotein cholesterol and apolipoprotein A-I levels.

We measured the percentage of slow-twitch (ST) muscle fibers in the lateral portion of the quadriceps femoris muscle in 41 healthy sedentary male controls, 35 active male joggers, and 26 male coronary heart disease (CHD) patients. We then compared these percentages with serum levels of total cholesterol (TC), triglycerides (TG), high density lipoprotein cholesterol (HDL-C) and apolipoprotein A-I (apo A-I) found in these 102 middle-aged men. The percentage of ST muscle fibers in all men correlated positively with serum HDL-C (r = 0.57, P less than 0.001) and with apo A-I (r = 0.60, P less than 0.001) and negatively with triglycerides (r = -0.43, P less than 0.001). The proportion of ST fibers in joggers (65%; 61-69%, 95% confidence interval) was higher (P less than 0.001) than in sedentary controls (48%; 44-52%) or in CHD patients (44%; 39-49%). Moreover, 89% of the joggers had a proportion of ST fibers higher than 50%, whilst in sedentary controls and in CHD patients these values were 46% and 38%, respectively. Positive correlations were found between the percentage of ST fibers and both HDL-C and apo A-I in controls (r = 0.33, P less than 0.05 and r = 0.34, P less than 0.05) and in joggers (r = 0.46, P less than 0.01, and r = 0.40, P less than 0.05), respectively. Negative correlations in controls (r = -0.34, P less than 0.05) and in CHD patients (r = -0.43, P less than 0.05) were also found between the percentage of ST fibers and serum TG.(ABSTRACT TRUNCATED AT 250 WORDS)