Use of hormone replacement therapy. Hormone replacement therapy may not always be right choice to prevent cardiovascular disease.
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Biomedical subjects
Publications and source records attributed to S Panico.
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BACKGROUND: High levels of androgens and estrogens have been reported to be associated with breast cancer. However, the multiplicity of factors that influence hormone levels and methodologic issues complicate the study of the relationship between steroid sex hormones and breast cancer. PURPOSE: Using an improved study design, we assessed prospectively the relationship between the principal steroid sex hormones in serum and the subsequent occurrence of invasive breast cancer in postmenopausal women. METHODS: Four thousand fifty-three healthy postmenopausal women aged 40-69 years, were enrolled from June 1987 through June 1992 in a prospective investigation of hormones and diet in the etiology of breast tumors (ORDET study) as part of a larger volunteer cohort of 10 788 premenopausal and postmenopausal women from Varese Province, northern Italy. At recruitment, blood samples were taken between 8:00 AM and 9:30 AM (after overnight fasting), and sera were preserved in -80 degree Celsius freezers. Women who had received hormone treatment in the 3 months prior to enrollment, who had bilateral ovariectomy, or who had a history of cancer or liver disease were not recruited. Twenty-five women in the final eligible cohort of postmenopausal women developed histologically confirmed, invasive breast cancer during the first 3.5 years of follow-up for the cohort (13 537 women-years). For each case subject, four control subjects were randomly chosen after matching for factors possibly affecting hormone preservation in serum. One case subject and eight control subjects were excluded because premenopausal hormonal patterns were found; thus, after also excluding the four control subjects matched to the ineligible case subject, we included 24 case and 88 control subjects. In the spring of 1994, stored sera of case and control subjects were assayed in a blinded manner for dehydroepiandrosterone sulfate and estradiol (E2) by in-house radioimmunoassay and for total and free testosterone and sex hormone-binding globulin by commercially available nonextraction iodination kits. Mean differences in risk factors were tested by analysis of variance for paired data. Relative risks (RRs) were estimated by conditional logistic regression analysis. All P values resulted from two-sided tests. RESULTS: Age-adjusted mean values of total testosterone, free testosterone, and E2 were significantly higher in case subjects than in control subjects: total testosterone, 0.34 ng/mL versus 0.25 ng/mL (P<.001); free testosterone, 1.07 pg/ml versus 0.77 pg/mL (P= .006); and E2, 25 pg/mL versus 22 pg/mL (P= .027). Age-adjusted RRs for breast cancer in increasing tertiles were as follows: for total testosterone, 1.0, 4.8, and 7.0 (P for trend =.026); for free testosterone, 1.0, 1.8, and 5.7 (P for trend=.005); and for total E2, 1.0, 7.1, and 5.5 (P for trend= .128). CONCLUSIONS AND IMPLICATIONS: This prospective study provides further evidence in support of the already established association between elevated estrogen levels and breast cancer. Even more importantly, it provides new evidence that high serum testosterone levels precede breast cancer occurrence.
This report analyzes the association between blood pressure and three indicators of peripheral androgenic activity (PIAAs): body fat distribution, hirsutism, and sebum production. Furthermore, it analyzes the associations among these PIAAs to understand whether they are indicators of the same androgenic pattern. The study was conducted among 314 healthy women, aged 35-69 years, participating in the baseline examination of the Study of Hormones and Diet in the Etiology of Breast Cancer (ORDET), an Italian cohort study of breast cancer. Body fat distribution was measured as the ratio of waist-to-hip circumference (waist-to-hip ratio). Three hirsutism scores were developed by use of factor analysis after nine areas of androgen-sensitive, pilo-sebaceum units of the body were examined. Sebum production was measured by a sebumeter. Results indicated a positive correlation between the waist-to-hip ratio and the lip hirsutism score (r = 0.157). Conversely, sebum production correlated negatively with both the lip hirsutism score (r = -0.154) and the waist-to-hip ratio (r = -0.153). By use of multiple regression and with adjustment for age and body mass index, the waist-to-hip ratio was found to be positively and significantly related to both diastolic and systolic blood pressure, whereas sebum production was inversely and significantly related to both diastolic and systolic blood pressure. The facial hirsutism score was positively related to systolic blood pressure, while the limb hirsutism score was inversely and significantly related to diastolic blood pressure. Finally, interrelationships among these markers of androgenic activity were found to be weak, suggesting that these markers may be under the influence of local metabolism of the androgenic steroids. Further hormonal analyses are needed to determine whether PIAA measures obtained in epidemiological settings are useful in study of androgenic patterns and blood pressure.
In this cross-sectional study we compared the abilities of lipoprotein(a) [Lp(a)], plasminogen activator inhibitor-1 (PAI-1), and tissue plasminogen activator (TPA) to discriminate between individuals with and without a history of stroke from among subjects in a metabolic ward. A total of 210 subjects (108 men and 102 women; mean age, 63.8 years; range, 31 to 86 years) provided plasma and DNA samples for the study. Of these, 51 men and 50 women had a history of ischemic stroke. The 109 subjects without a history of stroke were compared with those with such a history for major risk factors for ischemic events. Mean plasma TPA and PAI-1 levels significantly (P < .001) discriminated among subjects younger than 70 years with a history of stroke. The mean plasma Lp(a) level of stroke subjects (21.9 mg/dL) did not differ significantly from that of control subjects (15.2 mg/dL). However, among individuals < 70 years old, Lp(a) plasma levels > 50 mg/dL were more common among stroke patients (8 with versus 1 without, P < .01 by chi 2 test). A molecular variation in the 5' flanking region of the apo(a) gene that has been related to elevated Lp(a) plasma levels (G/A-914) was not strongly correlated with circulating levels of Lp(a), nor did Lp(a) levels correlate with a polymorphism of the apo(a) gene (G/A-21), which is strongly linked (P < .001) to the G/A-914 variation. In this setting, the relation between Lp(a) and cerebral ischemia appears to be limited to individuals below 70 years with elevated (> 50 mg/dL) plasma levels of the lipoprotein.
We evaluated the genotypes of the angiotensin-converting enzyme (ACE) gene in 101 subjects with and 109 subjects without a history of ischemic stroke. All were attending a metabolic ward. The two groups were compared for major risk factors for ischemic events. Genotypes were determined by polymerase chain reaction with oligonucleotide primers flanking the polymorphic region in intron 16 of the ACE gene. Deletion polymorphism of the ACE gene (DD genotype) was shown to be more common in subjects with a history of stroke than in those without (relative risk, 1.76; confidence intervals, 1.02 to 3.05). A positive family history for ischemic complications of atherosclerosis was also more common in subjects with documented events (relative risk, 1.99; confidence intervals, 1.10 to 3.59). DD genotype and a positive family history were strong independent discriminators of cerebral ischemia. Plasma levels of tissue-type plasminogen activator (TPA) and plasminogen activator inhibitor-1 help identify subjects with a history of cerebral ischemic episodes. When such fibrinolytic variables were included in the analysis, the DD genotype still strongly and independently discriminated subjects with a stroke history and significantly interacted with TPA levels > 10 ng/mL in such identification. We conclude that in subjects attending a metabolic ward, homozygosity for a deletion polymorphism of the ACE gene consistently discriminates subjects with a stroke history. Interaction with TPA improves such identification.
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The relative validity of multiple telephone 24-hour dietary recalls was evaluated in a feasibility study within the framework of a large prospective investigation on the cause of chronic disease in women. Forty-nine women were interviewed four times both face-to-face and by telephone. Comparison of the total number of calories and intake of protein, carbohydrate, total and saturated fats, cholesterol, fiber, sodium, potassium, calcium, vitamin A, and vitamin C as estimated by multiple face-to-face and telephone interviews revealed an acceptable relative validity for the telephone procedure. Analysis of the position variation in the distribution (percent agreement) comparing the two procedures showed that a change in the distribution of none or one quintile occurs in more than 70% of individuals for all nutrients but vitamin C (69.4%), cholesterol (61.2%), and vitamin A (51.4%). Correlation coefficient analysis showed similar results. Adjustment for nutrient densities did not affect the overall results. Multiple 24-hour telephone dietary recalls appear to be a valid alternative to face-to-face interviews in population studies.
The effect of heparin and partially desulfated heparin derivatives on thrombin and PAF-induced adhesion of PMNs to the endothelium was studied either by a fluorescence image analysis or by 111In-labeled PMNs. The results observed with these two techniques consistently indicated that heparin and O-des-heparin inhibited PMN adhesion in a dose-dependent manner. Moreover, N-des-Hep and N-O-des-Hep, even if less effective, also inhibited the adhesion of PMNs when used at high concentrations. The effect of heparin and heparin derivatives was not directed to endothelial cells but rather to PMNs, as shown by the absence of inhibitory effects, when heparins were preincubated with endothelium.
We evaluated 106 subjects with and 109 subjects without a history of ischemic stroke. All were attending a metabolic ward. The two groups were compared for major risk factors for ischemic events. A positive family history for ischemic complications of atherosclerosis was more common in subjects with a history of stroke than in those without; moreover, plasma levels of plasminogen activator inhibitor-1 (PAI-1) and tissue-type plasminogen activator (TPA) were higher in patients with documented previous events. A strong positive significant correlation was found between TPA and PAI-1 levels, and an interaction between age and TPA was observed when the sample was stratified according to ages being above or below 70 years. When the patient population was analyzed according to the number of ischemic events, it was found that 62 of the 106 subjects with a history of stroke had experienced more than one ischemic event. Under these conditions, the levels of TPA and PAI-1 still correlated with the occurrence of previous ischemic episodes. As in the whole patient sample, TPA was the strongest discriminator. We conclude that in subjects attending a metabolic ward, TPA and PAI-1 levels consistently help identify subjects with a history of cerebral ischemic episodes and that TPA is the strongest discriminator.
The association between serum uric acid and hypertension was evaluated in a sample of male workers in southern Italy enrolled in the Olivetti Heart Study, an ongoing longitudinal epidemiological investigation on risk factors for coronary heart disease carried out at the Olivetti factory in the suburban area of Naples. Participants were screened at baseline (1975) and at five year (1980) and 12 year (1987) follow-up examinations. The present report focuses on 619 male workers for whom information on coronary heart disease risk factors was available both at baseline and 12 year follow-up examination. At baseline, after excluding hypertensive participants (systolic blood pressure (SBP) > or = 140 mmHg and/or diastolic blood pressure (DBP), > or = 90 mmHg and/or on antihypertensive therapy; n = 72), serum uric acid was positively and significantly related to age, SBP, DBP, body mass index (BMI), serum total cholesterol (CHOL) and serum triglycerides (TG) in 547 normotensive participants. At 12 year follow-up examination, hypertension was defined by SBP > or = 140 mmHg and/or DBP > or = 90 mmHg and/or being on antihypertensive therapy. Multiple logistic regression analysis showed an independent positive association between serum uric acid levels and development of hypertension (RR = 1.23, 95% CI = 1.07-1.39; p = 0.011) after adjustment for age, BMI, CHOL and TG. Furthermore, according to more severe degrees of hypertension (SBP > or = 160 mmHg and/or DBP > or = 95 mmHg and/or being on antihypertensive therapy), the relative risk to develop hypertension was still significant (RR = 1.19; CI = 1.01-1.38; p = 0.051).(ABSTRACT TRUNCATED AT 250 WORDS)
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The present report focuses on the association between baldness pattern and coronary heart disease risk factors in 872 male factory workers from southern Italy participating in an epidemiological study. Participants were divided according to presence or absence of baldness and baldness pattern. Participants with fronto-occipital baldness (male-type baldness) (n = 280) characterized by hair loss centered over the vertex with an m-shaped frontal-temporal recession had, on the average, higher serum cholesterol and blood pressure compared to participants with no baldness (n = 321) and/or participants with just frontal baldness (n = 273). For serum cholesterol, a significant interaction was detected between age and fronto-occipital baldness (i.e. the association between fronto-occipital baldness and elevated levels of serum cholesterol became weaker with age). No interaction was detectable between age and fronto-occipital baldness for blood pressure. The results of this cross-sectional study indicate that male-type pattern of baldness is associated with elevated CHD risk profile, and that this relation between age and serum cholesterol differs in younger compared to older men.
This report analyzes the role age in the association between alcohol consumption and blood pressure in a large sample (n = 6165) of Italian men and women, aged 20 to 59 years, who participated in a multicenter study on risk factors for arteriosclerosis. Age-stratified analysis indicated that both men and women aged 50 to 59 years showed the strongest positive association between alcohol consumption and blood pressure. While in men the association between systolic blood pressure and alcohol consumption increased linearly with age, in women the association between systolic blood pressure and alcohol increased sharply in the oldest (50 to 59 year) age group.
The relationship between coffee consumption and blood lipids was analyzed in a sample of 900 male workers of southern Italy participating in the Olivetti Heart Study. In the univariate analysis, coffee drinkers (n = 856) had higher values for body mass index (P < or = 0.05) and number of cigarettes smoked per day (P < or = 0.001) and lower levels of serum high-density-lipoprotein cholesterol (P < or = 0.05), compared to noncoffee drinkers (n = 44). In addition, coffee consumption (cups/d) was positively related to serum triglyceride levels (r = 0.105, P < or = 0.01) and cigarette smoking (r = 0.491, P < or = 0.01), and was inversely related to age (r = -0.122, P < or = 0.01). After multivariate adjustment, coffee consumption remained significantly related to age, cigarette smoking, and body mass index (data not shown). After stratification for smoking status, a significant positive linear trend between coffee consumption and serum total cholesterol was observed only in smokers. No significant trend was observed for serum triglycerides and high-density-lipoprotein cholesterol with coffee intake according to smoking status. This finding suggests that the relationship between coffee consumption and serum total cholesterol may change with the smoking status.
The longitudinal association between a number of coronary heart disease risk factors and the experience of a natural disaster (earthquake) was analyzed in a group of workers participating in a longitudinal epidemiologic investigation. The 5-year follow-up examination was interrupted by a major earthquake, and examinations were resumed 2 weeks after the quake. Participants screened after the quake had, on average, higher heart rates, serum cholesterol, and triglycerides than participants examined before the quake; these differences were independent from the coronary heart disease risk factor values measured 5 years previously during the baseline examination. The data collected during the 12-year examination indicated that the observed short-term increase in serum lipids and heart rate was not present long-term (7 years after the quake). These longitudinal data indicate that exposure to a natural disaster can be associated with short-term increases in heart rate, serum cholesterol, and triglycerides but that there is no apparent long-term effect on these coronary heart disease risk factors.
In spite of their important impact on populations, a number of diseases--all types of cancer and coronary heart disease in women--are "rare" events for statistical analysis and often analyzed in designs affected by selection and information biases, such as case-control studies. Large cohort studies based on the storage of biological specimens appear to be the most suitable solution for identifying risks for those diseases. Progetto ATENA, a study on the etiology of major chronic diseases in women is based on this design. Ten thousand women, aged 30-69 years, living in the area of the city of Naples, free of cancer and cardiovascular disease, are being recruited over a four-year period. Ten per cent of the cohort is being randomly selected from the electoral roles, the rest will be volunteers. Information on dietary habits, reproductive history, familiarity for chronic disease, active smoking habits and passive smoking exposure, physical activity, and socio-demographic data are being collected. Clinical data such as blood pressure, anthropometry, and electrocardiogram are also taken. All the participants provide biological samples of blood (fasting drawing) and urine (timed morning spot). The biological samples are processed in order to explore the main areas under study (nutritional markers, metabolism, endocrinology, genetics, environmental exposure markers, thrombogenesis). The samples are stored in liquid nitrogen (-196 degrees C) as soon as the blood and urine processing have been finished. An appropriate follow-up information system on the health status of the participants is being set up to estimate incidence and mortality rates.
Activation of 202 and (2'-5')(A)n synthetase genes after injection of interferon (IFN)-inducing, double-stranded, poly rI:rC was compared in various mouse strains. The 202 mRNA level increased 4.5- to 10-fold in DBA/2, BALB/c, and C3H/HeJ mice, whereas in C57BL/6 mice it rose only to about that in untreated DBA/2, BALB/c, and C3H/HeJ mice. To determine whether this low level was due to a reduced transcription rate, a nuclear "run-on" assay was performed with NIH 3T3 cells or BLK cells derived from C57BL/6 mice. IFN-alpha increased the 202 mRNA transcription severalfold in NIH 3T3 cells only, and that of a (2'-5')(A)n synthetase gene in both cell lines. The possibility that an alteration in transacting factors could be responsible for this difference was examined. For this purpose the 5' terminal flanking region (called the b segment, about 0.8 kb) of the 202 gene was linked to a heterologous reporter gene--chloramphenicolacetyl-transferase (CAT) and transfected into normal or transformed NIH 3T3 cells and into various C57BL/6-derived cell lines. IFN-alpha induced strong CAT activity in transfected normal or transformed NIH 3T3 cells, but a much lower activity in those from C57BL/6 mice. The b segment contains an IFN-responsive element (ISRE) (35 bp) homologous to that present in several other IFN-inducible genes. Three tandem copies of the 202 ISRE were linked to an enhancerless SV40 early promoter driving an influenza virus hemagglutinin (HA) cDNA segment. No increase in HA mRNA expression was detected in the transfected BLK cell line derived from C57BL/6 mice following IFN treatment, whereas in the NIH 3T3 cell line, the IFN treatment resulted in a 2.5-fold increase. These and other results suggest that C57BL/6 mice and cell lines derived from them might carry defective transacting factors impairing the ability of IFN-alpha to activate the 202 gene without impairing its ability to activate a (2'-5')(A)n synthetase gene.