Mediterranean Diet and Oxidative Stress: A Relationship with Pain Perception in Endometriosis.

BACKGROUND: Endometriosis is a chronic and inflammatory disease associated with pelvic pain. Dietary changes may be therapeutic for chronic inflammatory processes, reducing visceral input. The aim was to evaluate the role of dietary changes according to the Mediterranean Diet (MD) on pain perception in endometriosis and their relationship with oxidative stress. METHODS: in this prospective study, we included 35 endometriosis women. At baseline (T0) and after 3 (T1) and 6 (T2) months from the start of the diet, we investigated pain intensity with VAS (Visual Analogue Scale, from 0 to 10), vitamin profile, and oxidative stress. RESULTS: we found a significant increase in the diet score (p < 0.001). At T1, patients reduced pain in terms of dyspareunia (p = 0.04), non-menstrual pelvic pain (p = 0.06), dysuria (p = 0.04), and dyschezia (p < 0.001). Dyspareunia (p = 0.002) and dyschezia (p < 0.001) were further significantly reduced also at T2. We observed a significant positive correlation between lipid peroxidation and VAS non-menstrual pelvic pain and dysuria and a significant negative correlation between Oxygen radical absorbance capacity and VAS non-menstrual pain and dyschezia. CONCLUSIONS: our findings show a clear tendency toward a relationship between pain relief in endometriosis and MD. This appears promising to treat endometriosis-related symptoms and could be considered a new effective strategy for chronic pain management in the long term.

Impact of COVID-19 Pandemic on Women's Health and Obstetric Outcomes after Assisted Reproduction: A Survey from an Italian Fertility Center.

BACKGROUND: the restrictive measures that were adopted during three waves of the COVID-19 pandemic had an impact on both the emotional state and lifestyle of the general population. We evaluated the impact of COVID-19 pandemic on lifestyles and emotional states of women planning assisted reproductive technology (ART), and whether these changes affected ART outcomes. METHODS: quantitative research, using a web-based survey, was performed on 289 Caucasian women. RESULTS: In preconception, we observed higher percentage of women with positive obstetric outcomes who reduced body weight (52.4% vs. 27.2%, p = 0.09). Over 60% of women with positive outcomes practiced physical activity vs. 47% of women with negative outcomes (p = 0.03), as well as having better quality of sleep (45% vs. 35%), and a more solid relationships with their partners (65.1% vs. 51.7%, p = 0.03). Women who increased their intake of whole grains, fruits, vegetables, and legumes (p < 0.05), according to the Mediterranean diet, showed positive outcomes. We observed that participants who experienced "very much" or "extreme" anxiety, sadness, and fear (p < 0.05) during pandemic were clearly more numerous in the group with negative pregnancy outcomes. CONCLUSIONS: healthy lifestyle together with a positive emotional state in preconception can positively influence the obstetric outcomes after ART.

Atherosclerosis and Endometriosis: The Role of Diet and Oxidative Stress in a Gender-Specific Disorder.

Background: Accelerated atherosclerosis in patients with endometriosis has been hypothesised, and lifestyle improvement might control cardiovascular risk. We explored cardiometabolic markers and oxidative stress and evaluated the effects of the Mediterranean Diet (MD) in modulating these markers. Methods: In this prospective study, we included 35 women with endometriosis. At baseline (T0) and after 3 (T1) and 6 (T2) months from the start of the diet, we investigated cardiometabolic parameters, lifestyle and oxidative stress. Results: After a 3-month intervention with MD, we observed a significant reduction in total cholesterol (p = 0.01) and LDL-c (p = 0.003). We observed at T1 an increase in B12 and E vitamins, folate and zinc. After 6 months, zinc (p = 0.04) and folate (p = 0.08) increased in comparison to T0. A reduction in homocysteine from T0 to T1 (p = 0.01) was found. After 3 months, an increase in Rapid Assessment of Physical Activity tool 1 (RAPA) (p < 0.001) and RAPA 2 was observed (p = 0.009). We observed high levels of oxidative stress markers at baseline. After 6 months of MD, a significant improvement in lymphocyte Reactive Oxygen Species (ROS) (p < 0.001) and total antioxidant capacity was observed (p = 0.02). Conclusions: The improvement of lifestyle, and in particular the Mediterranean dietary intervention, allowed the improvement of the metabolic and oxidative profile and overall health-related quality of life.

Preconception period in women and men undergoing Assisted Reproduction: A gender approach for reproductive health.

OBJECTIVE: To evaluate lifestyle and risk factors playing a role in increasing the burden of cardiovascular diseases and to increase attention of clinicians who should envision a broader preconception approach in ART, not only in women but also in men. STUDY DESIGN: In this cross-sectional study we investigated 90 Caucasian couples, referred to the Internal Medicine Clinic at the Assisted Reproductive Technology Centre, in order to better define in preconceptional period their cardiovascular risk profile, based on metabolic parameters and lifestyle behaviours. RESULTS: We observed two-fold increase of overweight in men in comparison to women (p = 0.006). Values of waist ≥ 94 cm in men and ≥ 80 cm in women were present in 53.3% of men and 32.2% of women (p = 0.007). Similarly, values of WHR according to gender cut-off, were present in 64.4% of men and in 32.2% of women (p < 0.0001). In men we observed a significantly higher prevalence of hypertension (p = 0.02), significantly lower HDL-c (p = 0.001) and higher levels of total cholesterol (p = 0.01), LDL-c and triglycerides (p = 0.001). Sedentary behaviour was observed in about 60% of both genders. Alcohol consumption was reported by 42.2% of men and 26.7% of women (p = 0.04) and smokers were more prevalent among women (26.7%) than men (24.4%). We observed a lower adherence to Mediterranean Diet related to consumption of red meat and meat products (p = 0.02), as well as of legumes consumption (p = 0.01) in men, whereas sweet/pastries (p = 0.05) and fruits (p = 0.06) in women. Men and women with normal BMI, waist and WHR, showed a higher Mediterranean diet adherence in comparison to overweight/obese study population(p < 0.001). Finally, higher education level predicted the higher Mediterranean diet adherence in both gender (p = 0.01 for men, p = 0.03 for women). CONCLUSIONS: This study paid attention on preconceptional health in couples planning ART. Women have a greater biological role in childbearing, whereas the role of men is underestimated. The need to conceive through ART offers a window of opportunity not only to evaluate cardiovascular profile and lifestyle factors in couples prior to conception, but also to manage comorbidities and promote health behaviours in order to improve fertility and health outcomes in both women and men at short and long-term.

Role of endometriosis in defining cardiovascular risk: a gender medicine approach for women's health.

The relationship between endometriosis and subclinical atherosclerosis represents an emerging topic in women's health, as women with endometriosis are at higher risk of cardiovascular disease later in life. We investigated metabolic parameters and indirect endothelial markers related to atherosclerosis, in women suffering from stage III/IV of endometriosis compared with women without endometriosis. The study population comprised 643 women: 92 women (14.3%) with stage III/IV of endometriosis and 551 (85.7%) without endometriosis. By analyzing biohumoral parameters we observed a significant increased total cholesterol (p = 0.01), LDL-C (p = 0.01), triglycerides (p = 0.05) and homocysteinaemia (p = 0.04), lower vitamin B6 and folate (p = 0.07 and p = 0.03, respectively) values, and higher high-sensitive C reactive protein (p = 0.05) concentrations in stage III/IV in comparison to those observed in women without endometriosis. After adjustment for traditional cardiovascular risk factors, the poorer lipid profile (total cholesterol, LDL-C), as well as Lipoprotein (a), remained significantly associated with severity of endometriosis (p = 0.01 and p = 0.03, respectively). Our findings highlight the role of endometriosis as a gender-specific cardiovascular risk factor. The clinical relevance of our study lies in identifying women with stage III/IV of endometriosis at higher risk of atherosclerotic disease, who could benefit from an early cardiovascular screening to control future cardiovascular risk.

5-Methyltetrahydrofolate and Vitamin B12 Supplementation Is Associated with Clinical Pregnancy and Live Birth in Women Undergoing Assisted Reproductive Technology.

The homocysteine pathway in the preconception period should be evaluated to highlight micronutrient deficiencies and warrants optimal multivitamin supplementation, before Assisted Reproduction, as preconception care. We conducted a retrospective study aimed at investigating the role of vitamin B complex (5-methyltetrahydrofolate, vitamin B12, vitamin B6) supplement use compared with the role of only folic acid supplement use, in relation to clinical pregnancy and live birth in infertile women undergoing homologous ART. We investigated 269 Caucasian women referred to the Centre for Assisted Reproductive Technology for homologous ART. In these women, 111 (Group A) were daily supplemented with vitamin B complex and 158 (Group B) with only folic acid. In group A the mean number of Metaphase II oocytes and the 2PN Fertilization Rate were higher in comparison to group A (p = 0.04; p = 0.05, respectively). A higher percentage of women in group A had a clinical pregnancy and live birth in comparison to group B (p = 0.01; p = 0.02, respectively). Vitamin B complex supplementation remained independently associated, after multivariable adjustment, with clinical pregnancy (OR 2.03, p = 0.008) and live birth (OR 1.83, p = 0.03). Women supplemented with 5-MTHF and vitamin B12, have a higher chance of clinical pregnancy and live birth in comparison to those supplemented with only folic acid.

Ectopic Fat Depots and Cardiometabolic Burden: A Possible Dangerous Liaison in Women Planning Assisted Reproduction.

Objective: We evaluated cardiometabolic burden in women planning assisted reproduction in order to identify subgroups at higher risk of pregnancy complications and cardiovascular disease. Materials and methods: In this cross-sectional study we investigated 60 infertile women with BMI≥25 kg/m2 referred to the Center for Assisted Reproduction. All women underwent metabolic, anthropometric parameters and ultrasound evaluation of ectopic fat depots. Results: All women had waist ≥80 cm. We found that 93.3% of women had pathological subcutaneous, 58.3% visceral and 80% para-perirenal fat; all women had fatty liver. Visceral fat and severity of steatosis were significantly related to the presence of metabolic syndrome (OR =5.7; p=0.03).A significant negative correlation between low HDL-c and para-perirenal fat (p<0.0001), a significant positive correlation with fasting plasma glucose and para-perirenal fat (p=0.001) were found. We observed a significant positive correlation between visceral fat and hs-CRP (p=0.002), HOMA-IR (p=0.04) and triglycerides (p=0.002), a significant negative correlation with HDL-c (p=0.05). Conclusion: This study by highlighting a clinically "dangerous liaison" between ectopic fat depots and metabolic/inflammatory markers, might permit to identify women with a worse metabolic phenotype and encourage lifestyle changes for improving their general and reproductive health together.

Impact of cardiovascular burden on coagulation pathway in apparently healthy women planning oocyte donation.

BACKGROUND: Hormonal fertility treatments are associated with increased coagulation factors inducing procoagulant milieu and possibly thrombotic risk. OBJECTIVE: To assess coagulation by ROTEM and coagulation tests in apparently healthy infertile women before oocyte donation procedure. METHODS: We enrolled 51 women (Assisted Reproductive Technology Centre, Florence). ROTEM and coagulation parameters were assessed before the start of infertility treatment. RESULTS: We divided women in 3 groups according to the number of cardiovascular risk factors: Group A (n = 10), Group B (n = 16), and Group C (n = 25). By considering ROTEM Extem test, a significantly increased of MCF, TPI, and G were observed in groups B (p = 0.005, p = 0.03, and p = 0.007) and C (p = 0.01, p = 0.05, and p = 0.005) in comparison to group A. As regards ROTEM Intem test, the TPI and G values were significantly higher in groups B and C in comparison to group A (p < 0.01). MCF by Fibtem test significantly increased in groups B and C than in group A (p = 0.004 and p = 0.002, respectively). FVIII, vWF:Ag and D-dimer values significantly increase according to the presence of≥2 risk factors. CONCLUSIONS: Data from coagulative assessment permit to sensitively identify women with potentially procoagulable state, which represents a risk factor of thromboembolic event during hormone treatment.

Homocysteine, vitamin B status and MTHFR polymorphisms in Italian infertile women.

OBJECTIVE: The purpose of this study was to evaluate the vitamin B status related to the homocysteine pathway and the prevalence of polymorphisms of the MTHFR gene in infertile women programming homologous or heterologous ART. STUDY DESIGN: We investigated 393 consecutive Caucasian women, referred to the Internal Medicine Clinic at the Center for Assisted Reproductive Technology, in order to be framed for their vascular risk before starting homologous or heterologous (oocyte donation) procedures. Total homocysteine, Vitamin B12, folate and vitamin B6 were measured. The women were divided into quartiles of serum concentration of folate, vitamin B12 and vitamin B6. The C677T and A1298C polymorphisms of the MTHFR gene were genotyped by an electronic microchip technology. RESULTS: Sixty-one women (15.5%) had hyperhomocysteinemia, 22.9% had reduced levels of vitamin B12, 4.1% had reduced levels of serum folate and 0.1% had a deficiency of vitamin B6. Women in the highest quartile of vitamin B12 and folates had lower homocysteine ​​levels than women in the first and second quartiles (p < 0.0001). The homozygosity for MTHFR C677T polymorphism was detected in 33.3% (131), and heterozygosity for MTHFR C677T polymorphism in 45.3% (178) of women. We observed a significant association between hyperhomocysteinemia and 677T allele, but not 1298C, of the MTHFR polymorphisms (p = 0.04). CONCLUSIONS: We found inadequate vitamin B status related to the homocysteine ​​pathway in women planning Assisted Reproductive Technology. Moreover, interesting association was found regarding hyperhomocysteinemia in women carrying T allele of the C677T MTHFR polymorphism. A specific supplementation with 5-MTHF and adequate vitamin B12 concentrations before Assisted Reproductive Technology warrant serious consideration, in particular in women carrying T allele of the C677T MTHFR polymorphism.

The effects of COVID-19 lockdown on lifestyle and emotional state in women undergoing assisted reproductive technology: Results of an Italian survey.

PURPOSE: On March 8, 2020, the Italian Government implemented extraordinary measures to limit viral transmission of COV-19/SARS-CoV-2. We evaluated the impact of COVID-19 lockdown on lifestyle and emotional state in women planning infertility treatments. BASIC PROCEDURES: We performed a quantitative research study using a web-based survey, in 140 women referred to Assisted Reproductive Technologies Center. MAIN FINDINGS: We observed changes in body weight during lockdown in 80 % of women, and a significant increase in BMI in comparison to that observed before (p=.001). We observed a high percentage of non-adherence to the Mediterranean pattern during lockdown due to higher frequency of consumption of sweet/pastries, cheese and meat, rather than fruit, vegetables and legumes. Before lockdown 36.4 % women were snack consumers while during lockdown 55 % (p=.002). By considering individuals' attitude to snack consumption, we observed an increase related to boredom (p=<.0001) and anxiety (p=.05) during lockdown. Increased levels of anxiety and sadness were observed in about 30 %, and of boredom in 25 %. The percentage of women worried about their planning infertility treatment was more than 50 %. PRINCIPAL CONCLUSIONS: Quarantine-related restrictions strongly influenced lifestyle psychological behavior leading to an increased burden of cardiovascular disease.

Cardiometabolic and Thrombotic Risk Profile in Women Undergoing Oocyte Donation for Assisted Reproduction.

Background: The last two decades have seen a growing number of pregnancies in women who needed the donation of oocytes. With oocyte donation pregnancies, studies on obstetric outcomes among these women revealed an increased incidence of pre-eclampsia and pregnancy-induced hypertension. Furthermore, several studies have found a higher incidence of low birth weight, preterm birth, and delivery by cesarean section in oocyte donation rather than in women subjected to assisted reproduction techniques (ART) with autologous oocytes. Numerous studies have also shown a deep connection between cardiovascular and thrombotic risk factors and adverse pregnancy outcomes. In this setting, to strictly assess the preconceptional risk for women who undergo egg donation to achieve pregnancy, the aim of our study is to draw a detailed assessment of the vascular risk profile of patients with gamete donation ART indications through the evaluation of comorbidities and cardiometabolic and thrombophilic markers Materials and Methods: Patients undergoing ART with oocyte or sperm donation or double donation of gametes underwent a careful clinical assessment through a detailed personal and family anamnesis and they were evaluated for cardiometabolic and thrombophilic profile. Clinical and demographic characteristics, comorbidities, and biohumoral parameters were collected. The study was approved by the Regional Ethical Committee(Em 2018-017 CINECA 10189). Results: We evaluated 525 women. Around 73.1% were >40 years and 35% of them were older than 45 years. There was a high prevalence of dyslipidemias (58.1%), smoking habit (24.6%), a body mass index >25 in 28.6% of patients, a high abdominal circumference in 58.1% of cases, a prevalence of acquired thrombophilia in about 7% and hereditary of 19.2%. Around 39.2% of patients had total cholesterol >200 mg/dL, 19.5% had high-density lipoprotein <48 mg/dL and 43.6% had low-density lipoprotein >115 mg/dL, and 6.9% had triglyceride values >150 mg/dL. Conclusions: A careful assessment of the preconceptional status of patients undergoing ART programs with oocyte donation can be highly recommended.

Comorbidities, risk factors and maternal/perinatal outcomes in oocyte donation pregnancies.

RESEARCH QUESTION: To evaluate pre-existing comorbidities, obstetric risk factors and adverse obstetric and neonatal outcomes in pregnancies conceived by oocyte donation, compared with naturally conceived pregnancies or by conventional IVF/intracytoplasmic sperm injection (IVF/ICSI). DESIGN: This retrospective single-centre contemporary cohort study reviewed data from singleton deliveries at the University Hospital of Careggi, Florence, from 2009 to 2017. Maternal and perinatal outcomes were analysed. RESULTS: The study included 25,851 pregnancies and newborns: 276 (1.1%) children were conceived after oocyte donation, 925 (3.6%) after IVF/ICSI and 24,650 (95.4%) after natural conception. Women in the oocyte donation group were significantly older compared with IVF/ICSI and natural conception groups (P < 0.0001) and had a higher prevalence of chronic hypertension compared with the natural conception group (P = 0.0090). They were administered anticoagulant medications more frequently during pregnancy. The incidence of gestational hypertension was significantly higher than in natural conception (aOR 3.6) and IVF/ICSI pregnancies (aOR 2.7). The incidence of Caesarean section in oocyte donation pregnancies was higher than in natural conception and IVF/ICSI groups (aOR 3.4 and 2.3, respectively). An 11-fold increased risk of post-partum haemorrhage (PPH) was found in oocyte donation versus natural conception and an almost four-fold increased risk was found in oocyte donation versus IVF/ICSI; prematurity and low birthweight were more frequent after oocyte donation versus natural conception (aOR 2.4 and 1.8, respectively). CONCLUSIONS: Patients undergoing oocyte donation represent a group with increased comorbidities and risk factors for adverse obstetric outcomes. Oocyte donation seems to be independently associated with gestational hypertension and PPH. Pregnancies after oocyte donation warrant clinical surveillance with proper screening and, possibly, preventive strategies.

Lifestyle and Comorbidities: Do We Take Enough Care of Preconception Health in Assisted Reproduction?

Objective: The preconception period is largely neglected, whereas it represents an opportunity to identify and modify clinical and behavioral risks, particularly in infertile women characterized by an unfavorable vascular burden. The present study was performed to strengthen previous findings and to increase the awareness of clinicians who should envision a broader preconception approach in infertile women, beyond their reproductive health. Materials and methods: In this cross-sectional study, we investigated 1003 Caucasian women, referred to the Internal Medicine Clinic at the Assisted Reproductive Technologies Center, Florence. Results: A high prevalence of dyslipidemia (57.4%), overweight/obesity (29.1%) and, smoking habit (26.6%) were found. We provided evidence of unhealthy lifestyle habits, represented by a closer adherence to the Mediterranean diet in the 9.5% only and by a sedentary behavior in 73%. A significant correlation between the Mediterranean Diet score and both anthropometric and metabolic parameters was found. We also observed a lower score adherence with both metabolic syndrome and diabetes (for both p=0.02), but not with hypertension. Conclusion: Before infertility treatment, the correction and the management of modifiable and non-modifiable cardiovascular risk factors are mandatory and represent the main goal for a safe pregnancy, and lifetime women's health.

Assisted Reproductive Technology, Comorbidities, and Cardiovascular Risk: The Experience of an Italian Center.

BACKGROUND: A growing number of infertile women undergo assisted reproductive technology (ART). Older maternal age and the presence of comorbidities may affect cardiovascular (CV) women health. Safety aspects are central in risk assessment; we report the experience of internal medicine clinical setting at the ART center. MATERIALS AND METHODS: we investigated 243 infertile women (110 autologous and 133 oocyte donation [OD]); cardiometabolic parameters and CV risk factors were investigated during the clinical evaluation. RESULTS: We observed high prevalence of dyslipidemia (62.9%), smoking habit (27.5%), and body mass index (26.7%). Waist ≥80 cm was present in 65%, and waist to hip ratio (WHR) value >0.80 in 60.5% of women. The prevalence of migraine with aura, hypertension, and diabetes was 5.3%, 4.9%, and 4.5%, respectively. By evaluating variables according to autologous or OD ART, we observed that OD women were older than autologous, p < 0.0001. Overweight and obesity prevalence was higher in OD group; waist and WHR were significantly higher in autologous than in OD group (75% vs. 57%, p = 0.005, and 91.8% vs. 34.6%, p = 0.01, respectively). We observed a statistically significant unfavorable risk profile in OD in comparison to autologous women (p = 0.003); in particular, 60% of OD women carried 3-5 CV risk factors, and 8.3% carried at least six CV risk factors. CONCLUSIONS: The experience of an internal medicine clinic at the ART center strongly underlies the relevance of a careful medical evaluation before attempting ART, and suggests the opportuneness of a structured internal medicine clinic in every gynecology setting to better frame risk profile.

Thrombin potential and traditional coagulation assay: are they useful in exploring recurrent pregnancy loss risk?

: An adequate hemostatic balance is mandatory to get successful pregnancy. Obstetric complications, such as recurrent pregnancy loss (RPL), might be due to an impairment of placental perfusion possibly related to an underlying prothrombotic status. In this study, we used the global coagulation assay, calibrated automated thrombography and traditional coagulation assay to search for a possible underlying hypercoagulable status in women with history of RPL compared with uneventful pregnancy women. Thrombin generation, Fibrinogen, factor VIII (FVIII), Plasminogen Activator Inhibitor-1 (PAI-1) and von Willebrand factor levels were analyzed in 92 not pregnant unexplained RPL and 64 uneventful pregnancy women. In RPL women, significantly higher fibrinogen, FVIII and PAI-1 levels, and thrombin generation with respect to those observed in uneventful pregnancy women were found. By dividing the study population into quartiles of endogenous thrombin potential (ETP), a lower percentage of RPL women than uneventful pregnancy women in the second quartile was observed, whereas a higher percentage of RPL in comparison with uneventful pregnancy women in the third and fourth quartile was found (P = 0.009). Accordingly, the cut-off ETP of 1222.1 nmol/l was chosen; ETP above cut-off concentration was associated with more than two-fold increased risk of RPL (P = 0.008), also after adjustment for traditional risk factors (P = 0.009). We provided evidence of an underlying alteration of vascular network related to increased coagulation components, and fibrinolysis inhibitor levels in healthy women with history RPL; therefore, calibrated automated thrombography global assay and testing for FVIII and PAI-1 would be advisable in clinical practice to evaluate the hypercoagulable status in RPL women planning future pregnancy.

Searching for a common mechanism for placenta-mediated pregnancy complications and cardiovascular disease: role of lipoprotein(a).

OBJECTIVE: To investigate lipoprotein(a) [Lp(a)], a well known cardiovascular risk factor, in women with history of placenta-mediated pregnancy complications (PMPC) compared with healthy uneventful-pregnancy women (HW), and the role of LPA gene functional polymorphisms in modulating both Lp(a) levels and PMPC risk. DESIGN: Retrospective observational study. SETTING: University hospital. PATIENT(S): A total of 360 women with history of PMPC (154 preeclampsia [PE], 121 stillbirth [SB], and 85 small for gestational age [SGA]) and 270 HW. INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE(S): Lp(a) levels measurement and LPA +93C >T and +121G>A polymorphisms genotyping. RESULT(S): In PMPCs we observed higher Lp(a) levels than those found in HW and an association with PMPC risk, also after adjustment for age, familial history of cardiovascular disease, and traditional risk factors. By analyzing Lp(a) concentrations according to each pregnancy complication, we observed significantly higher Lp(a) levels in women with history of SB and PE, conferring 2.5-fold and 2-fold increased risks, respectively; no association with SGA was observed. Lp(a) concentrations progressively and significantly increased as LPA unfavorable allelic burden increased; unfavorable allelic burden influenced SB and PE risk. CONCLUSION(S): We evidenced, for the first time, an association between high Lp(a) concentrations and history of SB, and we confirmed the role of Lp(a) in PE risk; this well known atherothrombotic marker might represent one of the possible mechanisms shared by PMPC and cardiovascular disease.

ACE gene in pregnancy complications: Insights into future vascular risk.

OBJECTIVE: A history of placenta-mediated pregnancy complications (PMPCs) increases the risk of cardiovascular disease later in life, possibly related to the persistence of endothelial dysfunction. We performed this study in order to search for a common genetic background shared by women with a history of PMPC and vascular disorders, due to their common pathophysiologic pathway of endothelial dysfunction. METHODS: We analyzed the prevalence of seven polymorphisms in ACE, AGTR1, AGT, and eNOS genes, endothelial-function related, in 290 women with a history of premature cardiovascular events (CVDs), and in 367 women with a history of PMPC (preeclampsia (PE), stillbirth (SB), and small for gestational age (SGA)), compared with 300 healthy women (HW) who delivered after uneventful pregnancy (HW). RESULTS: ACE D allele frequency was similar between women with history of CVD and PMPC, and significantly higher than that observed in HW [OR (95% CI) 1.91, p = 0.002, and OR (95% CI) 2.18, p < 0.0001, respectively]. In women carrying ACE-240T or eNOS-786C allele, a two-fold increase in SB susceptibility was evidenced (p = 0.004 and p = 0.005, respectively). Women with a history of SB and premature CVD exhibited a significantly higher unfavorable allelic burden ≥ 3 in comparison to that observed in HW (p < 0.0001 and p = 0.002, respectively). CONCLUSIONS: Our findings demonstrate a common genetic background shared by women with a history of vascular disorders and PMPCs; pregnancy may be considered a window to future cardiovascular risk; therefore, "non-classic" genetic biomarkers of endothelial dysfunction might allow one to identify women who could have a greater benefit for an early cardiovascular screening and prevention.

Detrimental effects of niacin/laropiprant on microvascular reactivity and red cell deformability in patients with elevated lipoprotein(a) levels.

Several studies have found a beneficial effect of nicotinic acid on lipid profile, but there remains a limitation in the clinical use of nicotinic acid due to its side effects. In this study, 46 (F/M = 22/24, age = 58.74 ± 10.02 years) patients with Lp(a) ≥500 mg/L and with a previous arterial thrombotic event were treated with nicotinic acid/laropiprant (Tredaptive®). We found a significant reduction in the Lp(a) values at T1 (after 12 months), with a decrease of 32.3 % from baseline levels. At T1, 11 patients (23.9 %) showed Lp(a) levels to be <500 mg/L. PAT values were significantly decreased after treatment (2.13 ± 0.81 vs 1.74 ± 0.42, p = 0.001), showing a worsening of endothelial function in 27 (58.6 %) patients. A significantly higher number of patients had RHI <1.5 after the treatment [18 (39.1 %) vs 8 (17.4 %)]. Blood rheology worsened as ED was impaired (p < 0.0001) after 12 months, whereas WHV, plasma viscosity, and red cell aggregation did not show any significant differences in comparison to baseline. Patients with a worsening in microvascular reactivity in comparison to baseline showed a marked impairment in ED (0.3327 ± 0.037 vs 0.3091 ± 0.0351; p < 0.0001), while others showed only a mild, even though significant, reduction (0.3347 ± 0.0299 vs 0.3272 ± 0.0235; p = 0.044). In the light of the results of HPS2-THRIVE study, we may hypothesize that the addition of laropiprant to niacin might be responsible for these negative effects. In turn, these effects might explain, at least in part, the lack of a clinical net benefit of niacin/laropiprant in the trial.

Autoantibodies against ß1-Adrenergic Receptors: Response to Cardiac Resynchronization Therapy and Renal Function.

BACKGROUND: Cardiac resynchronization therapy (CRT) nonresponse remains a major clinical problem. Autoantibodies specific for the ß1-adrenergic (ß1-AAbs) and muscarinic (M2-AAbs) receptors are found in patients with chronic heart failure (HF) of various etiologies. MATERIALS AND METHODS: We retrospectively analyzed 73 HF patients (median age 67 years, 84% males, New York Heart Association II-IV, in sinus rhythm, left ventricular ejection fraction <35%) who received CRT defibrillator (CRT-D) from 2010 to 2013. ß1-AAbs and M2-AAbs were measured by enzyme-linked immunosorbent assay. Echocardiography was used to assess CRT response (reduction >15% in left ventricular end-systolic volume at 6 months follow-up). Renal function (RF) parameters (creatinine [Cr], blood urea nitrogen [BUN], estimated glomerular filtration rate [eGFR Modified Diet in Renal Disease], cystatin C [Cys-C], and neutrophil gelatinase-associated lipocalin [NGAL]) were also evaluated. RESULTS: A significantly higher percentage of patients positive for ß1-AAbs (OD sample/OD reference ratio >2.1) in nonresponders than in responder patients was observed (57% vs 27%, P = 0.004). No influence of M2-AAbs on CRT-D response was demonstrated. ß1-AAbs were predictive of a poor CRT-D response (odds ratio [OR] [95% confidence interval (CI)] 3.64 [1.49-8.88], P = 0.005), also after adjustment for RF parameters (OR [95% CI] 4.95 [1.51-16.26], P = 0.008) observed to influence CRT-D response (Cr P = 0.03, BUN P = 0.009, Cys-C P = 0.02). The positive rates of ß1-AABs in patients with abnormal blood level of Cr, eGFR, Cys-C, and NGAL were significantly higher than those with normal levels (P = 0.03, P = 0.02, P = 0.001, P = 0.007, respectively). CONCLUSIONS: Our study suggests that (1) the evaluation of ß1-AAb is useful to identify responders to CRT-D; (2) the presence of ß1-AAbs is in relationship with elevated renal function parameters.