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It has been well assessed that women have been widely under-represented in cardiovascular clinical trials. Moreover, a significant discrepancy in pharmacological and interventional strategies has been reported. Therefore, poor outcomes and more significant mortality have been shown in many diseases. Pharmacokinetic and pharmacodynamic differences in drug metabolism have also been described so that effectiveness could be different according to sex. However, awareness about the gender gap remains too scarce. Consequently, gender-specific guidelines are lacking, and the need for a sex-specific approach has become more evident in the last few years. This paper aims to evaluate different therapeutic approaches to managing the most common women's diseases., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

This case report describes an unusual case of a 69-year-old man who had an aortic valve replacement with the Smeloff-Cutter aortic mechanical prosthesis for aortic valve regurgitation at the age of 18 years. Echocardiography revealed a well-suited and well-functioning mechanical prosthesis. Even though the patient did not take any anticoagulant therapy or anti-platelets agent for 12 years, he was in surprisingly good health. To the best of our knowledge, this is the first time a mechanical 'ball-in-cage' valve prosthesis has lasted for such a long time without complications, although the patient has not been compliant with the anticoagulant therapy for 12 consecutive years., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: Caveolae are a prominent microdomain in endothelial cells and appropriate localization in caveolae is fundamental for endothelial nitric oxide synthase (eNOS) activity. Since the Glu298Asp variant in the eNOS gene alters caveolar localization of the corresponding enzyme, we tested the interaction between this variant and the rs4730751 polymorphism of the caveolin-1 (CAV-1) gene as related to arterial remodeling in end-stage renal disease (ESRD) patients., Methods: One hundred and thirty-three ethnically homogeneous ESRD patients underwent carotid ultrasonographic studies to measure intima-media thickness (IMT) and carotid cross-sectional area (CSA). Genotyping was performed by high-throughput allelic discrimination assays on real-time PCR., Results: Arterial remodeling was associated to the number of G alleles of CAV-1 polymorphism, GG homozygotes displaying an IMT and a CSA that were, respectively, 16% and 21% higher than those in patients without the risk allele (P < 0.012). In multiple linear regression analyses including the CAV-1 and the eNOS polymorphisms and adjusting for classical risk factors and risk factors peculiar to ESRD both polymorphisms were independent correlates of IMT (CAV-1: β = 0.20, P = 0.01; eNOS β = 0.25, P = 0.001) and CSA (CAV-1: β = 0.20, P = 0.01: eNOS β = 0.13, P = 0.09). Furthermore, strong interactions emerged between the two polymorphisms for explaining the variability in IMT (P = 0.001) and in CSA (P = 0.038) in these patients., Conclusion: Overall these findings form preliminary evidence that disturbed interaction between CAV-1 and eNOS may be of relevance for arterial disease in ESRD and perhaps in other human diseases.

Background: Reduced synthesis of nitric oxide (NO) is considered a major proatherogenic mechanism in patients with end-stage renal disease (ESRD), but genetic factors impinging on this mechanism have been little studied in this population., Methods: We tested the relationship between carotid intima-media thickness (IMT) and three endothelial NO synthase (eNOS) polymorphisms (G894T, T-786C, and 27-bp repeat in intron 4) in an ethnically and geographically homogeneous group of 147 patients with ESRD., Results: The IMT was significantly thicker (P = .01) in patients with the TT genotype (G894T polymorphism) than in patients with TG or GG genotypes, and a similar association was observed for the T-786C polymorphism (P = .02). These relationships remained statistically significant (P = .02 and .01), also in multivariate models including traditional and emerging risk factors for atherosclerosis. Moreover, there was a direct association between the number of risk alleles and IMT (no risk allele: 0.97 +/- 0.22 mm, 1 risk allele: 1.03 +/- 0.20 mm, 2 risk alleles: 1.07 +/- 0.22 mm, > or =3 risk alleles: 1.23 +/- 0.36 mm, P < .001) that remained statistically significant in a multiple regression model., Conclusions: In patients on dialysis the risk alleles of G894T and T-786C polymorphisms of the eNOS gene are associated with carotid atherosclerosis. The additive effect of the two polymorphisms may contribute to the severity of atherosclerosis independently of other risk factors and of endogenous substances that influence the NO synthesis in this population.

Background: E-selectin is a cell surface glycoprotein that mediates the adhesion of leucocytes to vessels endothelium, an important early step in the atherosclerotic process. End-stage renal disease (ESRD) is a highly atherogenic disease but it is unknown whether genetic polymorphism(s) in the E-selectin gene plays a role in the severity of arterial damage in this condition. Method. In this study, we tested whether the Leu554Phe variant in the E-selectin gene is linked to carotid atherosclerosis in 134 well-characterized ESRD patients. The frequency of this polymorphism was also measured in a population sample of the same geographical area., Results: A total of 84% patients had the CC genotype, 13% had the CT genotype, 3% had the TT genotype and this distribution did not differ from that in the control population. Intima-media thickness (IMT) (P = 0.01) and cross-sectional area (P = 0.02) were significantly higher in patients with the T-allele than in those without this allele. Furthermore, the degree of carotid stenosis was significantly higher (P = 0.02) in patients with T-allele than in CC patients. On multivariate analyses including the traditional and non-traditional risk factors, the Leu554Phe polymorphism was confirmed as an independent correlate of IMT (P = 0.02), cross-sectional area (P = 0.03) and carotid stenosis (P = 0.02)., Conclusion: In ESRD, the Leu554Phe polymorphism of E-selectin gene is associated with the severity of carotid atherosclerosis, suggesting that genetically-determined alterations in the E-selectin molecule may render ESRD patients with this gene variant particularly susceptible to the detrimental effects of inflammation on the arterial wall.

Background: We investigated whether the eNOS G/T polymorphism (Glu298Asp variant) is linked to the severity of carotid atherosclerosis and whether it is independent of asymmetric dimethylarginine (ADMA) in determining vascular damage in patients with end-stage renal disease (ESRD)., Methods: The eNOS polymorphism, ADMA, carotid intima-media thickness (IMT), and carotid artery (CCA) wall-to-lumen ratio (an indicator of arterial remodeling) were determined/measured in 131 patients with ESRD., Results: Both in the co-dominant and dominant model approach, IMT as well as CCA wall-to-lumen ratio were directly related to the T allele (P < or = .009) and these relationships held true in multiple linear regression analyses including ADMA and traditional and emerging risk factors. The relationship between eNOS genotypes and CCA wall-to-lumen ratio was further analyzed by a categorical approach and in a multiple logistic regression analysis, the odds ratio (OR) of increased CCA wall-to-lumen ratio was strongly associated to the T allele (codominant model: GG, OR = 1; GT, OR = 2.1; TT, OR = 8.2; P for trend = .01; dominant model: GG, OR = 1; GT and TT, OR = 2.7; P = .02)., Conclusions: The T allele of eNOS gene is an independent predictor of intimal lesions and vascular remodeling and it is associated with the severity of atherosclerosis independently of ADMA.

Background: Whether hypertension and left ventricular hypertrophy (LVH) are more prevalent in CAPD than in haemodialysis (HD) patients is still under discussion., Methods: To examine this problem we compared a group of 51 CAPD patients, with a group of 201 HD patients. The evaluation included the measurement of atrial natriuretic peptide (atrial natriuretic factor (ANF)), taken as indicator of volume status, and echocardiographic measurements., Results: CAPD patients were older, had been treated for a shorter time, and had lower serum albumin and phosphate than HD patients. Plasma ANF was higher (P<0.01) in CAPD (median 33.8 pmol/l (interquartile range 18.2-63.0)) than in HD patients (22.7 pmol/l (14.9-38.7)). Similarly, the left atrial volume was substantially higher (P<0.0001) in CAPD patients (49+/-22 ml) than in HD patients (37+/-17 ml), while the left ventricular end-diastolic diameter was similar in the two groups (CAPD 51+/-7 mm; HD 50+/-7 mm). Furthermore, left ventricular hypertrophy was more severe (P<0.0001) in CAPD (157+/-37 g/m(2)) than in HD patients (133+/-39 g/m(2)). The proportion of CAPD patients requiring antihypertensive drugs was markedly higher than that of HD patients (65 vs 38% P<0.001). Multivariate modelling showed that volume expansion and pressure load as well as serum albumin were independent predictors of left ventricular mass., Conclusions: Left ventricular hypertrophy is more severe in long-term CAPD patients than in HD patients. This finding is associated with evidence of more pronounced volume expansion, hypertension, and hypoalbuminaemia. Volume and pressure load along with factors associated with hypoalbuminaemia may aggravate LVH in uraemic patients on CAPD.

Background: Autonomic dysfunction and sleep apnoea are frequent complications of chronic renal failure. Since nocturnal hypoxaemia in sleep apnoea dampens autonomic reflexes, we postulated that altered autonomic control is in part linked to nocturnal hypoxaemia in uraemic patients., Methods: To test the hypothesis we performed continuous monitoring of O(2) saturation during night by pulse oximetry (Ohmeda-Biox) as well as echocardiography, 24-h ambulatory blood pressure monitoring, and standard tests of autonomic function in 50 patients on chronic dialysis (40 on haemodialysis and 10 on CAPD). For haemodialysis patients all studies were performed during a mid-week non-dialysis day., Results: Twenty-five patients had at least one episode of nocturnal hypoxaemia (median 13, interquartile range 4-31) while the other 25 patients had no episodes at all. Minimal and average SaO(2) were strongly interrelated (r = 0.64, P = 0.0001). In a multiple regression model, besides age, average nocturnal SaO(2) was the only independent predictor of the parasympathetic function. Similarly, average nocturnal SaO(2) was the only independent predictor of the autonomic response to standing. Sex, 24-h mean arterial pressure, body mass index, haematocrit, serum albumin, serum parathyroid hormone and duration of dialysis treatment had no independent effect on the autonomic tests. Interestingly, the average nocturnal SaO(2) and the interaction between the responses to the autonomic tests were independently related to posterior-wall thickness. This interaction term represented also the stronger independent predictor of the relative wall thickness of the left ventricle. In a multiple logistic regression model the interaction parasympathetic-sympathetic function was the only independent predictor of concentric remodelling or hypertrophy, while average nocturnal SaO(2) entered into this model (P = 0.03) only after exclusion of the autonomic function interaction term., Conclusions: Thus, altered cardiovascular autonomic control appears to be linked to nocturnal hypoxaemia and to concentric hypertrophy or remodelling in dialysis patients. Since nocturnal hypoxaemia is an established cardiovascular risk factor, altered autonomic control is a potential mechanism whereby hypoxaemia may trigger cardiovascular events in dialysis patients. It remains to be seen whether the link between nocturnal hypoxaemia and autonomic dysfunction is a causal one.