Hyperuricemia and Risk of Cardiovascular Outcomes: The Experience of the URRAH (Uric Acid Right for Heart Health) Project.

The latest European Guidelines of Arterial Hypertension have officially introduced uric acid evaluation among the cardiovascular risk factors that should be evaluated in order to stratify patient's risk. In fact, it has been extensively evaluated and demonstrated to be an independent predictor not only of all-cause and cardiovascular mortality, but also of myocardial infraction, stroke and heart failure. Despite the large number of studies on this topic, an important open question that still need to be answered is the identification of a cardiovascular uric acid cut-off value. The actual hyperuricemia cut-off (> 6 mg/dL in women and 7 mg/dL in men) is principally based on the saturation point of uric acid but previous evidence suggests that the negative impact of cardiovascular system could occur also at lower levels. In this context, the Working Group on uric acid and CV risk of the Italian Society of Hypertension has designed the Uric acid Right for heArt Health project. The primary objective of this project is to define the level of uricemia above which the independent risk of CV disease may increase in a significantly manner. In this review we will summarize the first results obtained and describe the further planned analysis.

Ambulatory blood pressure monitoring for risk stratification in obese and non-obese subjects from 10 populations.

Overweight clusters with high blood pressure (BP), but the independent contribution of both risk factors remains insufficiently documented. In a prospective population study involving 8467 participants (mean age 54.6 years; 47.0% women) randomly recruited from 10 populations, we studied the contribution of body mass index (BMI) to risk over and beyond BP, taking advantage of the superiority of ambulatory over conventional BP. Over 10.6 years (median), 1271 participants (15.0%) died and 1092 (12.9%), 637 (7.5%) and 443 (5.2%) experienced a fatal or nonfatal cardiovascular, cardiac or cerebrovascular event. Adjusted for sex and age, low BMI (<20.7 kg m(-2)) predicted death (hazard ratio (HR) vs average risk, 1.52; P<0.0001) and high BMI (> or = 30.9 kg m(-2)) predicted the cardiovascular end point (HR, 1.27; P=0.006). With adjustments including 24-h systolic BP, these HRs were 1.50 (P<0.001) and 0.98 (P=0.91), respectively. Across quartiles of the BMI distribution, 24-h and nighttime systolic BP predicted every end point (1.13 < or = standardized HR < or = 1.67; 0.046 < or = P<0.0001). The interaction between systolic BP and BMI was nonsignificant (P > or = .22). Excluding smokers removed the contribution of BMI categories to the prediction of mortality. In conclusion, BMI only adds to BP in risk stratification for mortality but not for cardiovascular outcomes. Smoking probably explains the association between increased mortality and low BMI.

Glycaemic fall after a glucose load. A population-based study.

BACKGROUND AND AIMS: A blood glucose (BG) fall after an oral glucose load has never been described previously at a population level. This study was aimed at looking for a plasma glucose trend after an oral glucose load for possible blood glucose fall if any, and for its impact on coronary mortality at a population level. METHODS AND RESULTS: In subjects from an unselected general population, BG and insulin were detected before and 1 and 2h after a 75-g oral glucose load for insulin sensitivity and ß-cell function determination. Blood pressure, blood examinations and left ventricular mass were measured, and mortality was monitored for 18.8±7.7 years. According to discriminant analysis, the population was stratified into cluster 0 (1-h BG < fasting BG; n=497) and cluster 1 (1-h BG ≥ fasting BG; n=1733). To avoid any interference of age and sex, statistical analysis was limited to two age-gender-matched cohorts of 490 subjects from each cluster (n=940). Subjects in cluster 0 showed significantly higher insulin sensitivity and ß-cell function, lower visceral adiposity and lower blood pressure values. Adjusted coronary mortality was 8 times lower in cluster 0 than 1 (p<0.001). The relative risk of belonging to cluster 1 was 5.40 (95% CI 2.22-13.1). CONCLUSION: It seems that two clusters exist in the general population with respect to their response to an oral glucose load, independent of age and gender. Subjects who respond with a BG decrease could represent a privileged sub-population, where insulin sensitivity and ß-cell function are better, some risk factors are less prevalent, and coronary mortality is lower.

The Emerging Risk Factors Collaboration: analysis of individual data on lipid, inflammatory and other markers in over 1.1 million participants in 104 prospective studies of cardiovascular diseases.

Many long-term prospective studies have reported on associations of cardiovascular diseases with circulating lipid markers and/or inflammatory markers. Studies have not, however, generally been designed to provide reliable estimates under different circumstances and to correct for within-person variability. The Emerging Risk Factors Collaboration has established a central database on over 1.1 million participants from 104 prospective population-based studies, in which subsets have information on lipid and inflammatory markers, other characteristics, as well as major cardiovascular morbidity and cause-specific mortality. Information on repeat measurements on relevant characteristics has been collected in approximately 340,000 participants to enable estimation of and correction for within-person variability. Re-analysis of individual data will yield up to approximately 69,000 incident fatal or nonfatal first ever major cardiovascular outcomes recorded during about 11.7 million person years at risk. The primary analyses will involve age-specific regression models in people without known baseline cardiovascular disease in relation to fatal or nonfatal first ever coronary heart disease outcomes. This initiative will characterize more precisely and in greater detail than has previously been possible the shape and strength of the age- and sex-specific associations of several lipid and inflammatory markers with incident coronary heart disease outcomes (and, secondarily, with other incident cardiovascular outcomes) under a wide range of circumstances. It will, therefore, help to determine to what extent such associations are independent from possible confounding factors and to what extent such markers (separately and in combination) provide incremental predictive value.

Serum uric acid shows a J-shaped trend with coronary mortality in non-insulin-dependent diabetic elderly people. The CArdiovascular STudy in the ELderly (CASTEL).

The relationship between serum uric acid (SUA) and risk of coronary heart disease (CHD) mortality remains controversial, particularly in diabetic subjects. The aim of the present study is to evaluate whether SUA independently predicts CHD mortality in non-insulin-dependent elderly people from the general population and to investigate the interactions between SUA and other risk factors. Five hundred and eighty-one subjects aged >/=65 years with non-insulin-dependent diabetes mellitus were prospectively studied in the frame of the CArdiovascular STudy in the ELderly (CASTEL). Historical and clinical data, blood tests and 12-year fatal events were recorded. SUA as a continuous item was divided into tertiles and, for each tertile, adjusted relative risk (RR) with 95% confidence intervals (CI) was derived from multivariate Cox analysis. CHD mortality was predicted by SUA in a J-shaped manner. Mortality rate was 7.9% (RR 1.28, CI 1.05-1.72), 6.0% (reference tertile) and 12.1% (RR 1.76, CI 1.18-2.27) in the increasing tertiles of SUA, respectively, without any difference between genders. In diabetic elderly subjects, SUA independently predicts the risk of CHD mortality in a J-shaped manner.

Pulse hypertension: a new component of the metabolic syndrome in elderly women?

The classification of arterial hypertension (HT) to define metabolic syndrome (MS) is unclear in that different cutoffs of blood pressure (BP) have been proposed. We evaluated the categorization of HT most qualified to define MS in relationship with coronary heart disease (CHD) mortality at a population level. A total of 3257 subjects aged > or =65 years were followed up for 12 years. MS was defined according to the criteria of the National Education Cholesterol Program using three different categories of HT: MS-1 (systolic blood pressure (SBP) > or =130 and diastolic blood pressure (DBP) > or =85 mm Hg), MS-2 (SBP > or =130 or DBP > or =85 mm Hg) and MS-3 (pulse pressure (PP) > or =75 mm Hg in men and > or =80 mm Hg in women). Gender-specific adjusted hazard ratio (HR) with 95% confidence intervals (CI) for CHD mortality was derived from Cox analysis in the three MS groups, both including and excluding antihypertensive treatment. In women with MS untreated for HT, the risk of CHD mortality was always significantly higher than in those without MS, independent of categorization; the HR of MS was 1.73 (CI 1.12-2.67) using MS-1, 1.75 (CI 1.10-2.83) using MS-2 and 2.39 (CI 3.71-1.31) using MS-3. In women with MS treated for HT, the HR of CHD mortality was significantly increased only in the MS-3 group (1.92, CI 1.1-2.88). MS did not predict CHD in men. In conclusion, MS can predict CHD mortality in elderly women with untreated HT but not in those with treated HT; in the latter, PP is the most predictive BP value.

Intra-erythrocyte cation concentrations in relation to the C1797T beta-adducin polymorphism in a general population.

Genetic variability in the ADD1 (Gly460Trp) and ADD2 (C1797T) subunits of the cytoskeleton protein adducin plays a role in the pathogenesis of hypertension, possibly via changes in intracellular cation concentrations. ADD2 1797CC homozygous men have decreased erythrocyte count and hematocrit. We investigated possible association between intra-erythrocyte cations and the adducin polymorphisms. In 259 subjects (mean age 47.7 years), we measured intra-erythrocyte Na(+) [iNa], K(+) [iK] and Mg(2+) [iMg], serum cations and adducin genotypes. Genotype frequencies (ADD1: GlyGly 61.5%, Trp 38.5%; ADD2: CC 80.4%, T 19.6%) complied with Hardy-Weinberg proportions. In men, ADD2 CC homozygotes (n=100) compared to T-carriers (n=23) had slightly lower iK (85.8 versus 87.5 mmol/l cells; P=0.107), higher iMg (1.92 versus 1.80 mmol/l cells; P=0.012), but similar iNa (6.86 versus 6.88 mmol/l cells; P=0.93). In men, iK, iMg and iNa did not differ according to ADD1 genotypes. In men, iK (R(2)=0.128) increased with age and serum Na(+), but decreased with serum total calcium and the daily intake of alcohol. iMg (R(2)=0.087) decreased with age, but increased with serum total calcium. After adjustment for these covariates (P

Triglycerides + high-density-lipoprotein-cholesterol dyslipidaemia, a coronary risk factor in elderly women: the CArdiovascular STudy in the ELderly.

BACKGROUND: The relationship between serum triglycerides (TG) level and the risk of coronary heart disease (CHD) mortality remains controversial. AIMS: To evaluate whether TG level is a risk factor for CHD in elderly people from general population, and to look for interactions between TG and other risk factors. METHODS: 3257 subjects aged >or= 65 years followed up for 12 years from the CArdiovascular STudy in the ELderly. Blood tests and anthropometric measurements were performed. Continuous items were divided into quintiles and, for each quintile, adjusted hazard ratio (HR) with 95% confidence interval (CI) for CHD mortality was derived by genders from Cox analysis. RESULTS: In women, the HR of being in the fifth rather than in the first quintile of TG was 2.45 (CI 1.48-3.51). In turn, high-density-lipoprotein cholesterol (HDL-C) inversely predicted CHD mortality; the HR of being in the first rather than in the fifth quintiles of HDL-C was 1.52 (CI 1.24-2.36). The risk of CHD mortality further increased up to 3.81 (CI 1.62-5.43) when high TG and low HDL-C were combined. No predictive role for either TG or HDL-C was detected in men. CONCLUSIONS: TG and HDL-C were independent predictors of CHD mortality in elderly women. The combination high TG + low HDL-C quadrupled the risk of CHD mortality in this gender only.

Context-dependency of the relation between left ventricular mass and AGT gene variants.

In the European Project on Genes in Hypertension (EPOGH), we investigated in three populations to what extent in a family-based study, left ventricular mass (LVM) was associated with the C-532T and G-6A polymorphisms in the angiotensinogen (AGT) gene. We randomly recruited 221 nuclear families (384 parents and 440 offspring) in Cracow (Poland), Novosibirsk (Russia), and Mirano (Italy). Echocardiographic LVM was indexed to body surface area, adjusted for covariables, and subjected to multivariate analyses, using generalized estimating equations and quantitative transmission disequilibrium tests in a population-based and family-based approach, respectively. We found significant differences between the two Slavic centres and Mirano in left ventricular mass index (LVMI) (94.9 vs 80.4 g/m2), sodium excretion (229 vs 186 mmol/day), and the prevalence of the AGT -6A (55.7 vs 40.6%) and -532T (16.8 vs 9.4%) alleles. In population-based as well as in family-based analyses, we observed positive associations of LVMI and mean wall thickness (MWT) with the -532T allele in Slavic, but not in Italian male offspring. Furthermore, in Slavic male offspring, LVMI and MWT were significantly higher in carriers of the -532T/-6A haplotype than in those with the -532C/-6G or -532C/-6A allele combinations. In women, LVMI was neither associated with single AGT gene variants nor with the haplotypes (0.19 < P <0.98). In Slavic offspring carrying the AGT -532C/-6G or -532C/-6A haplotypes, LVMI significantly increased with higher sodium excretion (+3.5 g/m2/100 mmol; P=0.003), whereas such association was not present in -532T/-6A haplotype carriers (P-value for interaction 0.04). We found a positive association between LVMI and the AGT -532T allele due to increased MWT. This relation was observed in Slavic male offspring. It was therefore dependent on gender, age and ecogenetic context, and in addition it appeared to be modulated by the trophic effects of salt intake on LVM.

Should pulse pressure become part of the Framingham risk score?

An increased pulse pressure suggests aortic stiffening. New evidence also suggests that pulse pressure is a more sensitive measure of risk than other indexes of blood pressure in middle-aged and older persons. The objective of the study was to relate pulse pressure to the risk of cardiovascular events in the general population, and to assess whether pulse pressure could improve the Framingham risk prediction. A total of 378 men and 391 women over the age of 50 years (mean 62.7 years) were followed. Sex-specific Framingham cardiovascular risk scores were derived from age, systolic pressure, diastolic pressure, total and HDL cholesterol, smoking status and the presence or absence of diabetes mellitus. The cutoff points used to develop a pulse pressure score were calculated by determining the percentile points corresponding to the blood pressure categories in the Framingham risk score. We calculated relative hazard rates by multiple Cox regression. After a median follow-up of 7.2 years (range: 11 months-15 years), a total of 148 cardiovascular events occurred. In Cox regression analysis, a 10 mmHg higher pulse pressure was associated with 31% (P<0.0001) increase in the risk for cardiovascular events (fatal and nonfatal) after adjustment for sex, age, total and HDL cholesterol, smoking and the presence of diabetes mellitus. After adjustment for the aforementioned risk factors, a one-point increment in the blood pressure and pulse pressure scores was associated with a 40 and 48% (both P<0.0001) increase in the risk of fatal and nonfatal cardiovascular events, respectively. When both the blood pressure and pulse pressure scores were forced into a Cox model, only the pulse pressure score remained statistically significant (P<0.0001) with a relative hazard rate of 1.37 (CI: 1.16-1.69). These prospective data suggest that pulse pressure may improve the Framingham risk prediction among middle-aged and older individuals. Further studies, especially in the Framingham cohort, are warranted.

Total cholesterol and mortality in the elderly.

OBJECTIVE: To evaluate, at a population level, whether total cholesterol (TC) is a risk factor of mortality. To verify whether or not this is true for both genders. DESIGN: Population-based, long-lasting, prospective study. SETTING: Institutional epidemiology in primary care. SUBJECTS: A total of 3257 subjects aged 65-95 years, recruited from Italian general population. INTERVENTION: None. MAIN OUTCOME MEASURES: Total cholesterol was measured, analysed as a continuous variable and then divided into quintiles and re-analysed. For each quintile, the multivariate relative risk (RR) of mortality adjusted for confounders was calculated in both genders. Stratification of mortality risk by TC quintiles, body mass index and cigarette smoking was also performed in both genders. RESULTS: Total cholesterol levels directly predicted coronary mortality in men [RR being in the fifth rather than in the first quintile: 2.40 (1.40-4.14)] and any other mortality in women. It also inversely predicted miscellaneous mortality in both genders. This trend was more evident when low cholesterol was associated with malnutrition or smoking. CONCLUSIONS: High TC remains a strong risk factor for coronary mortality in elderly men. On the other hand, having a very low cholesterol level does not prolong survival in the elderly; on the contrary, low cholesterol predicts neoplastic mortality in women and any other noncardiovascular mortality in both genders.

Pulse pressure and coronary mortality in elderly men and women from general population.

The aim of this work was to evaluate whether pulse pressure (PP) in elderly people is a better predictor of coronary mortality than systolic and diastolic blood pressure taken alone. For this aim, 3282 elderly subjects aged >or=65 years were studied in a population-based frame. Blood pressure was repeatedly measured and averaged; historical data, anthropometrics, blood tests and 14-year coronary mortality were recorded. Statistics included analysis of covariance, Cox analysis and bivariate vectorial analysis. Coronary mortality in women was predicted by PP (1.01 excess risk/mm Hg PP) and was significantly higher in the 3rd than in the 1st tertile of PP (relative risk 2.90); neither systolic nor diastolic pressure taken alone influenced mortality. When systolic and diastolic pressures were both entered into a Cox model, the former had a positive and the latter a negative effect on survival, confirming a prognostic role of PP. For any given level of systolic pressure, mortality was inversely associated with diastolic pressure. Finally, the mean vector representing both systolic and diastolic pressures of non-surviving women was characterised by higher systolic and lower diastolic components than in non-surviving. No significant trend of mortality in relation to either systolic blood pressure or PP was observed in men. In conclusion, the combination of systolic and diastolic pressure called PP is an independent predictor of coronary mortality in elderly females, and a better predictor than systolic or diastolic pressure alone.

Heritability of left atrial size in the Tecumseh population.

BACKGROUND: Little is known about the determinants of atrial size, and no study has analyzed whether genetic factors are involved in the pathogenesis of LA enlargement. MATERIALS AND METHODS: We studied the heritability of echocardiographic left atrial size in 290 parents from the Tecumseh Blood Pressure Study and 251 children from the Tecumseh Offspring Study. All data from the parents and children were obtained at the same field office in Tecumseh, USA. Left atrial dimension was determined echocardiographically in accordance with American Society of Echocardiography guidelines with the use of leading-edge-to-leading-edge measurements of the maximal distance between the posterior aortic root wall and the posterior left atrial wall at end systole. RESULTS: For correlation between the left atrial dimensions of the parents and their offspring, several models were generated to adjust the atrial dimensions in both groups for an increasing number of clinical variables. After removing the effect of age, gender, height, weight, skinfold thickness, and systolic blood pressure, parent-child correlation for left atrial size was 0.19 (P = 0.007). Further adjustment for left ventricular mass and for measuring left ventricular diastolic function increased the correlation to 0.25 (P = 0.001). CONCLUSIONS: The present data indicate that heredity can explain a small but definite proportion of the variance in left atrial dimension.

Weak effect of hypertension and other classic risk factors in the elderly who have already paid their toll.

The aim of the CASTEL, a population-based (n=3282) prospective study which began 14 years ago, was to identify those items which had a prognostic impact in the elderly, and to evaluate whether the typical cardiovascular risk factors, particularly arterial hypertension, play a role after the age of 65 years. Initial screening, final follow-up and annual detection of mortality were performed. Mantel-Hanszel approach and multivariate Cox model were used for statistics. Cardiovascular mortality was 23.3% in normotensive, 23.3% in borderline, and 25% in the sustained hypertensive subjects (insignificant difference). In women, the incidence of stroke and coronary artery disease weakly depended on pulse pressure. Historical stroke and myocardial infarction predicted cardiovascular mortality in women; diabetes, uricaemia and high heart rate in men. In the very old, the predictors were less numerous, and blood pressure was not a predictor whatsoever; pulse blood pressure and murmurs at the neck were especially predictive in women, historical heart failure, proteinuria and tachycardia in men, historical stroke and myocardial infarction, pulmonary disease, left ventricular hypertrophy, diabetes and uricaemia in both genders. The elderly have a different cardiovascular risk pattern compared to younger people. Hypertension is not a predictor of coronary and stroke mortality. Prognosis depends on pulse pressure rather than on the label 'hypertension'. Hypercholesterolaemia is not a risk factor. This could simply indicate that elderly persons are the survivors in a population where significant mortality has already made its mark, eliminating those with the worst risk pattern. The two genders have a different risk profile due to sex-specific susceptibility to risk factors.

Genetic contribution to the variance in left ventricular mass: the Tecumseh Offspring Study.

OBJECTIVE: To estimate the contribution of heredity to the variance in left ventricular mass (LVM), and to ascertain whether genetic factors may interact with non-genetic factors in promoting LVM growth. SUBJECTS AND SETTING: The study population consisted of 290 healthy parents and 251 healthy children living in Tecumseh, Michigan, USA. MAIN OUTCOME MEASURE: Correlation of parents' LVM with offspring's LVM adjusting for a number of clinical variables. METHODS: LVM in parents and offspring was measured with M-mode echocardiography by the same investigators. RESULTS: Parents unadjusted LVM was unrelated to offspring unadjusted LVM, but after removing the confounding effect of age, sex, anthropometric measurements, systolic blood pressure, plasma insulin and urinary sodium excretion, parent-child correlation for LVM was 0.28 (P = 0.006). The relative contribution of parental-adjusted LVM and of several offspring phenotypic and environmental variables on offspring LVM was evaluated by multivariable regression analysis. When age, gender, anthropometric measurements and systolic blood pressure were accounted for, adjusted LVM of parents explained only 1.6% of the total variance in offspring LVM. However, after inclusion of insulin and urinary sodium in the model heredity explained 7.6% of the total variance in offspring LVM, and its predictive power was second only to that of child's height. Furthermore, an interactive effect of parental LVM with offspring systolic blood pressure was found on child's left ventricular mass. CONCLUSION: Heredity can explain a small, but definite proportion of the variance in LVM. Higher blood pressure favors the phenotypic expression of the genes that regulate LVM growth.

Predictors of stroke mortality in elderly people from the general population. The CArdiovascular STudy in the ELderly.

Stroke occurs particularly frequently in elderly people and, being more often disabling than fatal, entails a high social burden. The predictors of stroke mortality have been identified in 3282 subjects aged > or = 65 years, taking part in the CArdiovascular STudy in the ELderly (CASTEL), a population-based study performed in Northeast Italy. Historical and clinical data, blood tests and 14-year fatal events were recorded. Continuous items were divided into quintiles and, for each quintile, adjusted relative risk (RR) with 95% confidence intervals [CI] was derived from multivariate Cox analysis. Age, historical stroke (RR: 5.2; 95% CI: 3.18-8.6) and coronary artery disease (RR: 1.38; CI: 1.18-2.1), atrial fibrillation (RR: 2.40; CI: 1.42-4.0), arterial hypertension (RR: 1.33; CI: 1.15-1.76), systolic blood pressure > or = 163 mmHg (RR: 1.84; CI: 1.20-2.59), pulse pressure > or = 74 mmHg (RR: 1.50; CI: 1.13-2.40), cigarette smoking (RR: 1.60; CI: 1.03-2.47), electrocardiographic left ventricular hypertrophy (RR: 1.72; CI: 1.10-2.61), impaired glucose tolerance (IGT, RR: 1.83; CI: 1.10-3.0), uric acid (UA) > 0.38 mmol/l (RR: 1.61; CI: 1.14-2.10), serum potassium > or = 5 mEq/l (RR: 1.70; CI: 1.24-2.50) and serum sodium < or = 139 mEql/l (RR: 1.34; 1.10-2.10) increased the risk of stroke. In the CASTEL, stroke was the first cardiovascular cause of death. Some independent predictors usually unrelated to stroke mortality (namely pulse pressure, pre-diabetic IGT, UA and blood electrolytes disorders) have been identified.

Pulse pressure: an independent predictor of coronary and stroke mortality in elderly females from the general population.

The aim of this paper is to evaluate whether pulse pressure is an independent risk factor for coronary and stroke mortality in 3282 subjects (1281 males and 2001 females) aged +/- 65 years, taking part in the CArdiovascular STudy in the Elderly (CASTEL). After dividing subjects into tertiles of pulse pressure, adjusted relative risk (RR) and confidence intervals (CI) for 14-year coronary and stroke mortality was evaluated for each tertile. Among females, coronary mortality rate was 2.7% in the first tertile of pulse pressure, 4.7% in the second (RR 1.38, 95% CI [1.15-2.66]) and 6.2% in the third (RR 2, CI [1.20-3.51]). Stroke mortality was 3.6%, 4.1% (RR 1.23, CI [1.02-2.23]) and 8.3% (RR 2.27, CI [1.37-3.74]), respectively. This trend was recognizable in normotensive, borderline and sustained hypertensive women, where mortality increased with rising pulse pressure. No relationship was found between pulse pressure and mortality in males. In elderly women, pulse pressure was a good predictor of coronary and stroke mortality, even superior to the label of hypertension. No matter how any given pulse pressure level was obtained, it was more predictive of both coronary and cerebrovascular mortality than belonging to a normo- or hypertensive category.

Blood pressure and metabolic profile after surgical menopause: comparison with fertile and naturally-menopausal women.

In 1978 a random sample (367 men and 568 women aged 18-65 years) taken from the general population of a north-eastern Italian town was screened for cardiovascular risk; 16 years later, the women were invited to a second screening. Three groups were identified at the initial screening (fertile, naturally menopausal and surgically menopausal) and four in the longitudinal study (137 remained fertile during the whole study, 205 became naturally menopausal, 56 were ovariectomised and 127 were already going through the menopause). The protocol included a questionnaire, blood pressure (BP) measurement, and blood exams. Continuous variables were adjusted for confounders. Systolic BP, prevalence of hypertension, cholesterol, glycaemia and uricaemia were similar, whereas diastolic and triglycerides (TG) were lower in surgically-menopausal than in fertile women (P < 0.001). No significant difference in 16 years' variation from baseline was observed between the four groups, although women who remained fertile showed the smallest increases. In particular, neither systolic or diastolic BP increases differed between the women who were oophorectimised and those who remained fertile. 'Fertile status' was rejected from the logistic equation of incidence of hypertension, and 'age of menopause' was also rejected when this analysis was repeated in ovariectomised women. New coronary artery disease (angina pectoris or myocardial infarction) was observed in one ovariectomised woman, in three naturally menopausal, and in 13 already menopausal women which seemed to reflect the age trend. No new cases were observed in women who remained fertile. In conclusion, in Italian women surgical menopause, similarly to natural menopause, is devoid of any negative prognostic effect. Journal of Human Hypertension (2000) 14, 799-805

The 24-hour rhythm of blood pressure differs from that of leg hemodynamics in orthotopic heart transplant recipients.

BACKGROUND: This study was aimed at investigating whether a circadian rhythm of peripheral resistance exists in patients with orthotopic cardiac transplantation (OCT) and whether it parallels that of blood pressure (BP). METHODS: BP and leg flow and resistance (plethysmography) were monitored for 24 hours in 13 denervated OCT recipients and 13 control patients with native heart, matched for casual blood pressure. RESULTS: On the basis of BP trend, control patients showed a BP reduction during sleep, whereas OCT recipients did not. Leg resistance was significantly lower and leg flow significantly higher during sleep than during waking in all patients, and the extent of the nocturnal decrease was similar in the two categories. CONCLUSIONS: The decrease in leg resistance in patients confined to bed for 24 hours is caused by peripheral mechanisms and does not depend on the autonomic control of the heart. The nocturnal decline in BP depends, on the contrary, on cardiac control and is lost in patients with denervated heart.