Marita Larsson

Endogenous steroids measured by high-specificity liquid chromatography-tandem mass spectrometry and prevalent cardiovascular disease in 70-year-old men and women

CONTEXT There is a need for increased knowledge about endogenous sex hormone levels and clinical outcomes of risk/benefit. Immunoassays have poor specificity to reliably measure low steroid concentrations in elderly. OBJECTIVE The objective of the study was to evaluate plasma steroid concentrations with regard to prevalent cardiovascular disease (CVD) in elderly, using mass spectrometry. SETTING The study was conducted at a university hospital research unit. DESIGN AND METHODS Plasma samples were analyzed from 202 70-yr-olds as part of a large population-based study, Prospective Investigation of the Vasculature in Uppsala Seniors. Twenty-eight of these had prevalent CVD. Eleven steroids were quantified, using liquid chromatography-tandem mass spectrometry. Women with current/previous menopausal hormone therapy (n = 35) were excluded. RESULTS Men without prevalent CVD had higher plasma 17beta-estradiol (E2), compared with women. Men with prevalent CVD, compared with those without, had lower 17-hydroxypregnenolone (17OHPregn), 17-hydroxyprogesterone, and higher estrone/androstenedione and E2/testosterone (T) (aromatase activity). Women with prevalent CVD had lower pregnenolone, 17OHPregn, and dehydroepiandrosterone (DHEA) but higher DHEA/17OHPregn, androstenedione/DHEA, E2/T, E2/estrone, and E2/SHBG. The aromatase index, E2/T, was higher for prevalent CVD in both sexes. Adjustment for statin use, smoking, and body mass index yielded additional significant differences in men, whereas some were lost in women. Logistic regression indicated strong associations between prevalent CVD and low 17OHPregn, adjusted odds ratio of 0.18, 95% confidence interval (0.06-0.61); P = 0.006, in women and low 17-hydroxyprogesterone, 0.45 (0.25-0.80); P = 0.007 in men, most likely caused by increased throughput (consumption) toward estrogen synthesis. CONCLUSIONS Prevalent CVD was associated with indications of lower androgen precursors, increased aromatase activity, and higher estrogen levels in both sexes. Results might represent an endogenous response to a condition of developing atherosclerosis, rather than a causative relationship. Furthermore studies are needed.

Risk factors for cardiovascular disease are increased in young adults treated with stem cell transplantation during childhood

Frisk P, Arvidson J, Larsson M, Naessén T. Risk factors for cardiovascular disease are increased in young adults treated with stem cell transplantation during childhood.

Thicker carotid intima layer, thinner media layer and higher intima/media ratio in women with recurrent depressive disorders: A pilot study using non-invasive high frequency ultrasound.

Abstract Objectives. Growing evidence indicates that depression is an important risk factor for coronary heart disease. Thus, the aim of the present study has been to investigate if young women with adolescent onset and recurrent depressive disorders have signs of carotid intima and media changes already at the age of 30. Methods. Fifteen subjects with adolescent onset recurrent depressive disorders, mean age 31.5 years, were compared to 20 healthy women with a mean age of 39.6 years. The thickness of carotid artery intima and media was assessed, using non-invasive high-frequency ultrasound (25MHz). Results. The subjects with recurrent depressive disorders had significantly thicker carotid intima, significantly thinner carotid media and significantly higher intima/media ratio despite the fact that they were about 10 years younger than the healthy women. Hypertension, obesity or smoking could not explain the results. Conclusion. Already at the age of 30, subjects with recurrent depressive disorders with adolescent onset do have early signs of carotid intima and media changes, indicating a less healthy artery wall, despite otherwise no clinical signs of cardiovascular disease.

Thicknesses of individual layers of artery wall indicate increased cardiovascular risk in severe pre‐eclampsia

To assess whether thicknesses of the intima and media in the common carotid artery (CCA) and the intima/media ratio (I/M) indicate an increased cardiovascular risk in non‐pregnant women with a history of previous severe pre‐eclampsia.

Artery wall layer dimensions during normal pregnancy: a longitudinal study using noninvasive high-frequency ultrasound

The vascular effects of normal pregnancy were investigated by estimating the intima and media thicknesses of the common carotid artery separately using 22-MHz ultrasound (Collagenoson, Meudt, Germany) in 57 healthy women with normal pregnancies and pregnancy outcomes, in all three trimesters and at 1 yr postpartum. A thick intima, thin media, and high intima-to-media (I/M) ratio are signs of a less healthy artery wall. Mean artery wall layer dimensions remained fairly constant during pregnancy, but the intima thickness and I/M thickness ratio appeared to improve (decrease) postpartum (P < 0.001 for both). The cardiovascular risk parameters of age, body mass index, and blood pressure in the first trimester were associated with higher I/M ratios, especially in the second trimester, whereas higher serum estradiol levels were significantly associated with a lower I/M ratio. Changes from the first to second trimesters in I/M ratio, taking into account differential changes in intima and media thickness, were significantly (P < 0.05-0.001) associated with all risk parameters tested except age, which was associated with increased intima thickness (P = 0.02). Associations with third trimester values and changes from first to third trimesters were similar but less apparent. Thus, fairly constant mean artery wall layer dimensions during pregnancy appeared to improve postpartum. However, higher age, body mass index, or blood pressure and lower serum estradiol levels in the first trimester appeared to negatively affect the artery wall, strongly suggesting that pregnancy has negative vascular effects in some women. A less likely explanation involves possible adaptation to physiological changes during and after pregnancy.

Individual Common Carotid Artery Wall Layer Dimensions, but Not Carotid Intima-Media Thickness, Indicate Increased Cardiovascular Risk in Women With Preeclampsia An Investigation Using Noninvasive High-frequency Ultrasound

Background— Preeclampsia (PE) is associated with increased risk of cardiovascular disease later in life. Ultrasound assessment of the common carotid artery intima–media thickness (IMT) during or after PE has not indicated any increased cardiovascular risk. Methods and Results— We used high-frequency ultrasound (22 MHz) to estimate the individual common carotid artery IMTs in 55 women at PE diagnosis and in 64 women with normal pregnancies at a similar stage. All were re-examined about 1 year postpartum. A thick intima, thin media, and high intima/media (I/M) ratio are signs of a less healthy artery wall. PE was associated with a significantly thicker mean common carotid artery intima, thinner media, and higher I/M ratio than in normal pregnancy (mean I/M difference, 0.21; 95% confidence interval, 0.17–0.25; P<0.0001). After adjustment for first trimester body mass index and mean arterial pressure, differences in intima thickness and I/M remained significant. About 1 year postpartum, these values had improved in both groups, but group differences remained significant (all adjusted P<0.0001). There were no significant differences in IMT between groups. In receiver-operating characteristic curve analysis, intima thickness and I/M were strongly predictive of prevalent PE (area under the curve, ≈0.95), whereas IMT was not (area under the curve, 0.49). Conclusions— The arteries of women with PE were negatively affected during pregnancy and 1 year postpartum compared with women with normal pregnancies, indicating increased cardiovascular risk. Estimation of intima thickness and I/M ratio seem preferable to estimation of common carotid artery IMT in imaging cardiovascular risk in PE. Results from this pilot study warrant further confirmation.

Tibolone low dose (1.25 mg/d) therapy and postural balance in elderly women

UNLABELLED Most hip fractures occur in subjects without osteoporosis and are associated with a fall. Conventional menopausal hormone therapy (HT) improves postural balance, which might explain the rapid reduction in hip fracture risk. It is unclear whether tibolone improves postural balance, which might determine its effects on peripheral fracture risk. OBJECTIVE To study the short-term effects of low-dose tibolone therapy on postural balance in elderly women. METHODS Eighty healthy women (70 evaluable), aged 60 years or more, were recruited through advertising in the local media. They were randomly allocated to receive either tibolone (1.25 mg/d) or placebo for 6 months. Postural balance was assessed as sway velocity, using a force platform. RESULT(S) Baseline characteristics, including serum estradiol values and postural balance, were similar in the two study groups. On average, the overall dosing compliance was very high, over 97% in both groups. After 6 months, sway velocity had decreased (improved) by 7.6% (-0.97 cm/s; P=0.16 vs. baseline) in the tibolone arm and by 2.5% (-0.30 cm/s; P=0.59 vs. baseline) in the placebo group. The difference 0.67 cm/s was not statistically significant (95% CI -2.44, 1.10; P=0.45). Adjustments for age, serum estradiol level and variable value at baseline, revealed similar results. CONCLUSIONS Short-term treatment with tibolone (1.25 mg/d), compared to placebo, did not significantly affect postural balance function in elderly women.

Association between angiogenic factors and signs of arterial aging in women with pre‐eclampsia

Pre‐eclampsia (PE) is associated with an increased risk of cardiovascular disease later in life. In cases with PE there is a substantial increase in levels of the antiangiogenic factor soluble fms‐like tyrosine kinase‐1 (sFlt‐1) and decreased levels of the proangiogenic factor placental growth factor (PlGF). Elevated levels of sFlt‐1 are also found in individuals with cardiovascular disease. The aims of this study were to assess levels of sFlt‐1, PlGF and the sFlt‐1/PlGF ratio and their correlation with signs of arterial aging by measuring the common carotid artery (CCA) intima and media thicknesses and their ratio (I/M ratio) in women with and without PE.

Low-dose tibolone (1.25 mg/d) does not affect muscle strength in older women

Objective: More than 50% of all fractures occur in people without osteoporosis. Hormone therapy increases bone density, improves postural balance, and reduces fracture risk in postmenopausal women. It is unclear whether tibolone, a synthetic steroid hormone drug, can improve muscle strength. Thus, the aim of this study was to study the effects of low-dose tibolone therapy on muscle strength in older women. Methods: Eighty healthy women (69 completed the study) 60 years or older were recruited through advertising in the local media. They were randomly allocated to receive either tibolone 1.25 mg/day or placebo for 6 months. The stand-up test was used to assess leg muscle strength and balance. Handgrip and leg muscle strength were measured using JAMAR and modified Cybex dynamometers. Results: Baseline characteristics, including serum estradiol values and muscle strength, were similar in the two groups. Compliance with the therapy regimen was very high, averaging more than 97% in both groups. After 6 months, mean values for handgrip strength, knee extensor strength, and average time to perform 10 stands were improved numerically in both groups compared with values during baseline. However, there were no significant differences in these parameters within or between groups, and differences remained nonsignificant after adjustment for age, serum estradiol, and baseline value. Conclusions: Short-term treatment with low-dose tibolone (1.25 mg/d) seems not to affect muscle strength in older women.

Serum Pentraxin 3 is associated with signs of arterial alteration in women with preeclampsia

BACKGROUND Preeclampsia (PE) in pregnancy is a state of exaggerated inflammation and is associated with an increased risk of cardiovascular disease (CVD) later in life. Levels of pentraxin 3 (PTX3), a novel inflammation marker, are increased during PE and in individuals with CVD. The primary aim of this study was to assess whether serum PTX3 in women with PE is associated with adverse arterial effects; a thicker intima and higher intima/media (I/M) ratio in the common carotid artery (CCA). METHODS Serum PTX3 levels were measured using commercially available enzyme-linked immunosorbent assay kits, and individual CCA intima and media thicknesses were estimated by 22MHz non-invasive ultrasound in 55 women at PE diagnosis and 64 women with normal pregnancies at a similar gestational age, and about one year postpartum. A thick intima, thin media and high I/M ratio indicate a less healthy artery wall. RESULTS During pregnancy serum PTX3 correlated positively with intima thickness and I/M ratio but negatively with media thickness (all p<0.0001), indicating adverse arterial effects. About one year postpartum, PTX3 levels had decreased in both groups and there remained no significant group difference or significant correlation with CCA wall layers. CONCLUSIONS Higher levels of serum PTX3 in women with PE were significantly associated with signs of adverse arterial effects during pregnancy, but not one year postpartum, supporting the rapid dynamics of PTX3.