ABSTRACT: OBJECTIVE: Reported associations between endogenous steroid hormone levels and cardiovascular disease in the older population have been contradictory. We evaluated plasma steroid concentrations in terms of the dimensions of the common carotid artery wall layers as a measure of the extent of atherosclerosis. METHODS: A subgroup of 70-year-old participants (32 women and 50 men) from the Prospective Investigation of the Vasculature in Uppsala Seniors study was investigated. All participants had assessments of common carotid artery wall layer parameters (intima thickness, media thickness, and intima-media thickness [IMT] ratio; measured by high-frequency ultrasound at 22 MHz) and endogenous steroid hormone concentrations (measured by liquid chromatography-tandem mass spectrometry). RESULTS: Low androgen levels, high aromatase enzyme activity (estrone [E1]/androstenedione and estradiol [E2]/testosterone), high E2/E1 ratio, and high estrogen levels (E1, E2, estriol, and E2/sex hormone-binding globulin) were consistently associated (often significantly) with a more unhealthy artery wall (thick intima, thin media, and high IMT ratio) in both sexes. Consistently strong associations were found between the aromatase index E2/testosterone and intima, media, and the IMT ratio. For IMT ratio, in both men (rs = 0.52) and women (rs = 0.58), P was <0.001 for both and remained significant after adjustment for cardiovascular disease risk factors and the Framingham risk score (both P < 0.01). CONCLUSIONS: Low androgens, high aromatase enzyme activity, and high estrogen levels are often significantly associated with an unhealthy artery wall on ultrasound. We suggest that the steroid hormone profile of older individuals with higher estrogens most probably reflects an endogenous response to developing atherosclerosis, rather than a cause-and-effect relationship. However, the reverse causality cannot be excluded.
Menopause (New York, N.Y.) 09/2012; · 3.08 Impact Factor
ABSTRACT: 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.
The objective of the study was to evaluate plasma steroid concentrations with regard to prevalent cardiovascular disease (CVD) in elderly, using mass spectrometry.
The study was conducted at a university hospital research unit.
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.
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.
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.
The Journal of clinical endocrinology and metabolism 02/2010; 95(4):1889-97. · 6.50 Impact Factor
ABSTRACT: The thickness of the arterial intima increases and that of the media decreases with increasing age and degree of atherosclerosis. Separate estimates of the individual intima and media layers might therefore be more appropriate than the commonly used method estimating the combined intima-media thickness (IMT).
One hundred consecutive 70-year-old subjects from the PIVUS study were investigated. Separate estimates of the thickness of the carotid artery intima and media wall layers were carried out noninvasively using 25MHz high-frequency ultrasound. Subjects with a diagnosis of cardiovascular disease (CVD), coronary heart disease (CHD), myocardial infarction (MI) or stroke had a significantly thicker intima layer (all P<0.0001) and a thinner media layer (all P<0.05) than healthy subjects. The intima/media thickness ratio also differed significantly between subjects with and without a diagnosis of CVD (0.43+/-0.20versus 0.75+/-0.48, P=0.0002). Subjects with hypertension or hyperlipidemia also had a thicker carotid intima than subjects without these diagnoses (P<0.0005 for both). None of the corresponding intima+media thickness values differed significantly. Similar results were obtained in women and men.
Separate assessment of carotid artery intima and media thickness using noninvasive high-frequency ultrasound appears to be of potential value, as a striking difference in intima thickness and the intima/media thickness ratio was found between subjects with and without CVD.
Atherosclerosis 01/2007; 189(2):393-400. · 3.79 Impact Factor