9 research outputs found
Gender differences in cardiovascular disease : an epidemiologic study of endocrine factors
The initial interst in coronary- heart disease research in the 1950s centered
primarily on men because of its emergence as a major cause of morbidity
and mortality in men around middle age. In women, the incidence of coronary
heart disease is low at younger age and increases after middle age, though the
occurrence remains lower in women than in men at all ages. The fact that cardiovascular
disease is the major cause of morbidity and mortality in women has
been recognized already for many years and the last decade much effort has
been put in describing and studying cardiovascular disease in women. Despite
the research that has been carried out on the differences in cardiovascular disease
between the sexes, the gender gap in coronary- heart disease occurrence is
not completely understood until now. 1
The work presented in this thesis aims at gaining insight into gender specific
issues of cardiovascular disease and the cause of the rising incidence of cardiovascular
disease in women after middle age by studying putative endocrine and
metabolic risk factors. Data from various population-based studies were used to
study these issues.
In chapter 2, studies on classical cardiovascular disease risk factors attenuating
the female advantage with regard to cardiovascular disease occurrence
are presented. Chapter 3 contains studies on sex specific determinants of cardiovascular
disease with a focus on sex steroids. In chapter 4, studies on alternative
endocrine cardiovascular disease risk factors in postmenopausal women
are described. In chapter 5, the results described in this thesis are placed in a
broader context, some methodological considerations are discussed, and views
on further research regarding gender specific issues of cardiovascular disease
are put forward
Menopause, postmenopausal hormone use and serum uric acid levels in US women--the Third National Health and Nutrition Examination Survey.
INTRODUCTION: Despite the substantial prevalence of gout in the ageing female population, female hormonal influence has not been comprehensively examined. We evaluated and quantified the potential independent association between menopause, postmenopausal hormone use and serum uric acid levels in a nationally representative sample of women. METHODS: Using data from 7662 women aged 20 years and older in the Third National Health and Nutrition Examination Survey (1988 to 1994), we examined the relation between menopause, postmenopausal hormone use and serum uric acid levels. We used multivariate linear regression to adjust for other risk factors for hyperuricaemia such as dietary factors, age, adiposity, alcohol use, renal function, hypertension and diuretic use. RESULTS: Menopause was associated with higher serum uric acid levels. After adjusting for covariates, serum uric acid levels among women with natural menopause and surgical menopause were greater than premenopausal women by 0.34 mg/dl (95% confidence interval [CI], 0.19 to 0.49) and 0.36 mg/dl (95% CI, 0.14 to 0.57), respectively. Current postmenopausal hormone use was associated with a lower serum uric acid level among postmenopausal women (multivariate difference, 0.24 mg/dl [95% CI, 0.11 to 0.36]). The serum uric acid levels increased with increasing age categories (crude difference between 20 to 29 years and 70 years and over = 1.03 mg/dl, p for trend < 0.001), but this increase was not present after adjusting for other covariates (p for trend = 0.66). CONCLUSIONS: These findings from a nationally representative sample of US women indicate that menopause is independently associated with higher serum uric acid levels, whereas postmenopausal hormone use is associated with lower uric acid levels among postmenopausal women. The age-associated increase in serum uric acid levels in women may be explained by menopause and other age-related factors
Progression of aortic calcification is associated with metacarpal bone loss during menopause: a population-based longitudinal study
offerosclerosis and osteoporosis are major causes of morbidity and
mortality in postmenopausal women and have been suggested to be
associated. No study has examined whether progression of atherosclerotic
calcification is associated with bone loss. In the present study, we
examined progression of aortic calcification, diagnosed by radiographic
detection of calcified deposits in the abdominal aorta, in relation to
metacarpal bone loss, as assessed by metacarpal radiogrammetry, during
menopause. Initially premenopausal women (n=236), aged 45 to 57 years at
baseline, were followed for 9 years. We additionally assessed the
cross-sectional association between the extent of aortic calcification and
metacarpal bone mass and density in 720 postmenopausal women. Twenty-five
percent of women going through menopause showed progression of aortic
calcification. The average loss of metacarpal bone mass among women with
progression of aortic calcification was 3.2 mm(2), and their loss of
metacarpal bone density was 7.2 mm(2) %, whereas in women without
progression of aortic calcification, these losses were 2.0 mm(2) and 5.6
mm(2) %, respectively, adjusted for age and years of follow-up (P<0.05).
Additional adjustment for age at menopause, body mass index, blood
pressure, smoking, diabetes mellitus, and use of hormone replacement
therapy, thiazide, and loop diuretics did not influence these results. In
postmenopausal women, a graded inverse cross-sectional association between
the extent of aortic calcification and metacarpal bone mass and density
was found. In conclusion, our results indicate that progression of
atherosclerotic calcification is associated with increased bone loss in
women during menopause
Subclinical hypothyroidism is an independent risk factor for atherosclerosis and myocardial infarction in elderly women: the Rotterdam Study
BACKGROUND: Overt hypothyroidism has been found to be associated with
cardiovascular disease. Whether subclinical hypothyroidism and thyroid
autoimmunity are also risk factors for cardiovascular disease is
controversial. OBJECTIVE: To investigate whether subclinical
hypothyroidism and thyroid autoimmunity are associated with aortic
atherosclerosis and myocardial infarction in postmenopausal women. DESIGN:
Population-based cross-sectional study. SETTING: A district of Rotterdam,
The Netherlands. PARTICIPANTS: Random sample of 1149 women (mean age +/-
SD, 69.0 +/- 7.5 years) participating in the Rotterdam Study.
MEASUREMENTS: Data on thyroid status, aortic atherosclerosis, and history
of myocardial infarction were obtained at baseline. Subclinical
hypothyroidism was defined as an elevated thyroid-stimulating hormone
level (>4.0 mU/L) and a normal serum free thyroxine level (11 to 25 pmol/L
[0.9 to 1.9 ng/dL]). In tests for antibodies to thyroid peroxidase, a
serum level greater than 10 IU/mL was considered a positive result.
RESULTS: Subclinical hypothyroidism was present in 10.8% of participants
and was associated with a greater age-adjusted prevalence of aortic
atherosclerosis (odds ratio, 1.7 [95% CI, 1.1 to 2.6]) and myocardial
infarction (odds ratio, 2.3 [CI, 1.3 to 4.0]). Additional adjustment for
body mass index, total and high-density lipoprotein cholesterol level,
blood pressure, and smoking status, as well as exclusion of women who took
beta-blockers, did not affect these estimates. Associations were slightly
stronger in women who had subclinical hypothyroidism and antibodies to
thyroid peroxidase (odds ratio for aortic atherosclerosis, 1.9 [CI, 1.1 to
3.6]; odds ratio for myocardial infarction, 3.1 [CI, 1.5 to 6.3]). No
association was found between thyroid autoimmunity itself an
Low levels of endogenous androgens increase the risk of atherosclerosis in elderly men: the Rotterdam study
In both men and women, circulating androgen levels decline with advancing
age. Until now, results of several small studies on the relationship
between endogenous androgen levels and atherosclerosis have been
inconsistent. In the population-based Rotterdam Study, we investigated the
association of levels of dehydroepiandrosterone sulfate (DHEAS) and total
and bioavailable testosterone with aortic atherosclerosis among 1,032
nonsmoking men and women aged 55 yr and over. Aortic atherosclerosis was
assessed by radiographic detection of calcified deposits in the abdominal
aorta, which have been shown to reflect intimal atherosclerosis. Relative
to men with levels of total and bioavailable testosterone in the lowest
tertile, men with levels of these hormones in the highest tertile had
age-adjusted relative risks of 0.4 [95% confidence interval (CI), 0.2-0.9]
and 0.2 (CI, 0.1-0.7), respectively, for the presence of severe aortic
atherosclerosis. The corresponding relative risks for women were 3.7 (CI,
1.2-11.6) and 2.3 (CI, 0.7-7.8). Additional adjustment for cardiovascular
disease risk factors did not materially affect the results in men, whereas
in women the associations diluted. Men with levels of total and
bioavailable testosterone in subsequent tertiles were also protected
against progression of aortic atherosclerosis measured after 6.5 yr (SD
+/- 0.5 yr) of follow-up (P for trend = 0.02). No clear association
between levels of DHEAS and presence of severe aortic atherosclerosis was
found, either in men or in women. In men, a protective effect of higher
levels of DHEAS against progression of aortic atherosclerosis was
suggested, but the corresponding test for trend did not reach statistical
significance. In conclusion, we found an independent inverse association
between levels of testosterone and aortic atherosclerosis in men. In
women, positive associations between levels of testosterone and aortic
atherosclerosis were largely due to adverse cardiovascular disease risk
factors
Markers of inflammation and cellular adhesion molecules in relation to insulin resistance in nondiabetic elderly: the Rotterdam study
Insulin resistance, which is highly prevalent in the elderly, is suggested
to be accompanied by an increased acute phase response. Until now, it is
unclear whether cellular adhesion molecules are involved in the clustering
of insulin resistance. In the present study, we examined the relationship
of insulin resistance (measured by postload insulin) with levels of
markers of inflammation and cellular adhesion molecules in a random sample
of 574 nondiabetic elderly men and women participating in the Rotterdam
Study. Associations were assessed by regression analysis, with ln-insulin
as the dependent variable [regression coefficient (95% confidence
interval)]. In our population, insulin was strongly and significantly (P <
0.001) associated with the markers of inflammation C-reactive protein
[1.52 (0.96-2.08)], alpha-1-antichymotrypsin [1.25 (0.82-1.69)], and IL-6
[2.60 (1.69-3.52)], adjusted for age and gender. Associations weakened, to
some extent, after additional adjustment for measures of obesity, smoking,
and cardiovascular disease. Insulin was associated with the soluble
intercellular adhesion molecule 1 [2.22 (1.29-3.16; P < 0.001)], whereas
no association with the soluble vascular cell adhesion molecule 1 was
found. The strength of the associations of insulin with C-reactive
protein, alpha-1-antichymotrypsin, IL-6, and soluble intercellular
adhesion molecule 1, as assessed by standardized regression coefficients,
was comparable with the strength of the associations of insulin with
high-density lipoprotein cholesterol, body mass index, and waist-to-hip
ratio. The results of this population-based study indicate that low-grade
inflammation and the cellular adhesion molecule soluble intercellular
adhesion molecule 1 are an integral part of insulin resistance in
nondiabetic elderly. These factors may contribute to the well-known
relationship between insulin resistance and cardiovascular disease risk
and might potentially become therapeutic targets in insulin resistant
subjects
Associations of C-reactive protein with measures of obesity, insulin resistance, and subclinical atherosclerosis in healthy, middle-aged women
Obesity, the insulin resistance syndrome, and atherosclerosis are closely
linked and may all be determinants of an increased acute-phase response.
In this study, we examined the relationship of C-reactive protein (CRP)
with measures of obesity, variables of the insulin resistance syndrome,
and intima-media thickness of the common carotid arteries in 186 healthy,
middle-aged women selected from the general population. Associations were
assessed by regression analysis. CRP was strongly associated with body
mass index (BMI) and waist circumference. CRP was also associated with
other variables of the insulin resistance syndrome, including blood
pressure, insulin, high density lipoprotein cholesterol, triglycerides,
apolipoprotein A1 (inversely), plasminogen activator inhibitor-1 antigen,
and tissue-type plasminogen activator antigen. Associations between CRP
and the variables of the insulin resistance syndrome disappeared after
controlling for BMI but remained significant for plasminogen activator
inhibitor-1 antigen only. The association of CRP with common carotid
artery intima-media thickness was weak and limited to ever-smokers. BMI
explained 29.7% of the variance of CRP, whereas common carotid artery
intima-media thickness explained only 3.7%. The results of this
population-based study indicate that adiposity is strongly associated with
CRP in healthy, middle-aged women. In this population, BMI accounted for
the relationship between CRP and other variables of the insulin resistance
syndrome. Further studies should determine whether losing weight
ameliorates the inflammatory state
Menopause, postmenopausal hormone use and risk of incident gout
Objective: To prospectively study the relation between menopause, postmenopausal hormone use and risk of gout, since female sex hormones have been postulated to decrease gout risk among women. Methods: In the Nurses' Health Study, the association between menopause, age at menopause, postmenopausal hormone use and risk of self-reported physician-diagnosed incident gout among 92 535 women without gout at baseline was examined. Multivariate proportional hazards regression analysis was used to adjust for other risk factors for gout such as age, body mass index, diuretic use, hypertension, alcohol intake and dietary factors. Results: During 16 years of follow-up (1 240 231 person-years), 1703 incident gout cases were recorded. The incidence rate of gout increased from 0.6 per 1000 person-years in women 45 years had a RR of 1.62 (95% CI 1.12 to 2.33) of gout compared with women with age at menopause 50-54 years. Postmenopausal hormone users had a reduced risk of gout (RR=0.82; 95% CI 0.70 to 0.96). Conclusion: These prospective findings indicate that menopause increases the risk of gout, whereas postmenopausal hormone therapy modestly reduces gout risk