The influence of environmental factors on premature ovarian insufficiency and ovarian aging.

Premature ovarian insufficiency and ovarian aging are complex conditions that affect women's reproductive health and overall well-being. They are both characterized by hypergonadotropic hypogonadism and infertility, and together affect about 1 in 100 women by the age of 40. This review explores the influence of environmental factors on the development and progression of premature ovarian insufficiency and ovarian aging. When referring to environmental factors, we include a wide range of external agents and conditions, including chemicals, socioeconomic factors and lifestyle choices. Through a review of the literature, we attempt to highlight the link between environmental factors and ovarian health. We examine the impact of endocrine-disrupting chemicals, such as bisphenol A and phthalates, on ovarian function and investigate the mechanisms by which these chemicals can disrupt hormone signaling pathways, leading to alterations in ovarian reserve, oocyte quality, and folliculogenesis. Moreover, we explore lifestyle factors like obesity, stress, smoking and alcohol in relation to their effects on ovarian aging. Epigenetic changes may play a crucial role in the prevalence of premature ovarian insufficiency. Understanding the impact of environmental factors on premature ovarian insufficiency and ovarian aging is very important in public and clinical health contexts. By identifying risk factors, healthcare providers can develop targeted and strategic prevention and intervention plans. Furthermore, this knowledge can promote reproductive health and minimize exposure to harmful environmental agents.

"Failing kidneys in a failing planet; CKD of unknown origin".

The 'alarm clock' for human beings in the era of climate medicine has rung. Original diseases have appeared, that could not be explained and attributed to common causes, which are suggested to be linked to global warming and environmental factors. Such an indolent disease is the chronic kidney disease of unknown cause (CKDu), introduced also as Mesoamerican or Uddanam nephropathy. Scientists equate the climate impact on kidneys with the canary in the coal mine; coal miners used to carry caged canaries with them, so that if poisonous gases, such as methane or carbon monoxide leaked into the mine-shaft, the gases would kill the canary before killing the miners; similarly, kidneys are injured before devastating and lethal complications occur in humans. In some regions of Central America, the deaths due to chronic kidney disease increased by 177% with a death toll being as high as over 20,000. It was first documented in animals that periodic heat and dehydration have a major role in causing chronic kidney disease. Based on that observation, it is advocated that young male agricultural workers in Central America and South Asia, develop renal disease by getting exposed to extreme heat repeatedly. The clinico-pathological characteristics of this type of kidney injury, do not belong to an existing classification, even though a form of tubulo-interstitial renal disease has been proposed. In this review, we will discuss about CKDu, its epidemiology and pathophysiological mechanisms, clinical presentation and diagnostic biomarkers and examine potential therapeutic options.

Cirrhotic Cardiomyopathy: The Interplay Between Liver and Cardiac Muscle. How Does the Cardiovascular System React When the Liver is Diseased?

It is widely known that liver cirrhosis, regardless of the etiologies is accompanied by severe hemodynamic changes. The principal pathophysiological mechanisms are the hyperdynamic circulation with increased cardiac output, heart rate along with reduced systemic vascular resistance. Thus, counteractive mechanisms may develop that eventually lead to systolic as well as diastolic dysfunction and rhythm disturbances, in order to keep a steady homeostasis in the human body. Literally, blunted contractile responsiveness to physical or pharmacological stress, impaired diastolic relaxation and electrophysiological changes, primarily QT interval prolongation, do occur progressively in a cirrhotic patient with no known preexisting cardiac disease. This condition is identified as cirrhotic cardiomyopathy (CCM), an entity different from that seen in alcoholic cardiac muscle disease. For the past decades, clinicians did study and attempt to understand the pathophysiology and clinical significance of this process. Indeed, various factors have been identified acting at the molecular and cellular level. Electrocardiography, echocardiography and various serum biomarkers are the main tools that help healthcare practitioners to point to the correct diagnosis. Noteworthy, the subjects that suffer from cirrhotic cardiomyopathy may progress to heart failure during invasive procedures such as surgery, insertion of a transjugular intrahepatic portosystemic shunting (TIPS) and liver transplantation. Besides, several studies have illustrated that CCM is a contributing factor, or even a precipitant, of hepatorenal syndrome (HRS), a conceivable reversible kidney failure in patients with liver cirrhosis and ascites. The treatment is the same as it is in the patients with liver cirrhosis and heart failure and there is no particular treatment for cirrhotic cardiomyopathy. Hence, it is of utmost importance to clearly comprehend the pathophysiology of this disease in order to design more accurate diagnostic tools and definitive treatments in a way to prevent the complications of cirrhosis and overt heart failure. The objective of this review is to describe in a comprehensive way the pathological alterations that occur in the cardiovascular system of cirrhotic patients. It will also point the limitations that remain in the diagnosis and treatment strategies and more importantly, this review will alert the clinicians in the modern era to further observe and record additional pathological changes in this subset of patients.

Automated office blood pressure is in agreement with awake and mean 24-hour ambulatory blood pressure at the lower blood pressure range.

Automated office blood pressure measurement eliminates the white coat effect and is associated with awake ambulatory blood pressure. This study examined whether automated office blood pressure values at lower limits were comparable to those of awake and mean 24-hour ambulatory blood pressure. A total of 552 patients were included in the study, involving 293 (53.1%) men and 259 (46.9%) women, with a mean age 55.0 ± 12.5, of whom 36% were treated for hypertension. Both systolic and diastolic automated office blood pressures exhibited lower values compared to awake ambulatory blood pressure among 254 individuals with systolic automated office blood pressure <130 mm Hg (119 ± 8 mm Hg vs 125 ± 11 mm Hg, P < .0001 and 75 ± 9 mm Hg vs 79 ± 9 mm Hg, P < .0001 for systolic and diastolic BPs, respectively). Furthermore, the comparison of systolic automated office blood pressure to the mean 24-hour ambulatory blood pressure levels also showed lower values (119 ± 8 vs 121 ± 10, P = .007), whereas the diastolic automated office blood pressure measurements were similar to 24-hour ambulatory blood pressure values. Our findings show that when automated office blood pressure readings express values <130/80 mm Hg in repeated office visits, further investigation should be performed only when masked hypertension is suspected; otherwise, higher automated office blood pressure values could be used for the diagnosis of uncontrolled hypertension, especially in individuals with organ damage.

The optimal use of automated office blood pressure measurement in clinical practice.

This evidence-based article endorses the use of automated office blood pressure (AOBP). AOBP is the most favorable office blood pressure (BP) measuring technique as it provides accurate readings with 3-15 mm Hg lower values than the casual conventional office measurements with auscultatory or semi-automated oscillometric devices and relates closely to awake ABP readings. The AOBP technique seems to be superior to conventional office BP in predicting hypertension-mediated organ damage and appears to be equally reliable to awake ABP in the prediction of cardiovascular (CV) disease. AOBP readings should be obtained either unattended, with the patient alone in the examination room, or attended with the presence of personnel in the room but with no talking to the patient, although this recommendation is not frequently followed in routine clinical practice. To optimize office BP readings, the type of device, the rest period before AOBP measurements (preceding rest), and the time intervals between measurements were evaluated. As AOBP readings have the advantage of removing many confounding factors, the authors propose to perform measurements with a preceding rest in all patients at the initial visit; if AOBP readings remain <130 mm Hg in subsequent visits, measurements could be accepted, otherwise, if are higher, patients should be evaluated by out-of-office BP measurements.

Automated office blood pressure measurements obtained with and without preceding rest are associated with awake ambulatory blood pressure.

Automated office blood pressure (AOBP) measurement, attended or unattended, eliminates the white coat effect (WCE) showing a strong association with awake ambulatory blood pressure (ABP). This study examined the difference in AOBP readings, with and without 5 minutes of rest prior to three readings recorded at 1-min intervals. Cross-sectional data from 100 randomized selected hypertensives, 61 men and 39 women, with a mean age of 52.2 ± 10.8 years, 82% treated, were analyzed. The mean systolic AOBP values without preceding rest were 127.0 ± 18.2 mm Hg, and the mean systolic AOBP values with 5 minutes of preceding rest were 125.7 ± 17.9 mm Hg (P = .05). A significant order effect was observed for the mean systolic BP values when AOBP without 5 minutes of preceding rest was performed as the first measurement (130.0 ± 17.7 vs 126.5 ± 16.2, P = .008). When we used a target systolic AOBP ≥ 130 mm Hg, awake ABP yielded lower readings, while at a target systolic AOBP value of < 130 mm Hg higher awake ABP values were obtained. Our findings indicate that systolic AOBP can be initially checked without any preceding rest and if readings are normal can be accepted. Otherwise, when AOBP is ≥ 130 mm Hg, measurements should be rechecked with 5 minutes of rest.

Attended Versus Unattended Automated Office Blood Pressure: A Systematic Review and Meta-analysis.

INTRODUCTION: Automated office blood pressure (AOBP) has been proposed for blood pressure (BP) assessment in the office because it shows a strong association with the awake ambulatory BP. However, it remains unknown whether the presence or absence of an observer modulates AOBP readings. AIM: To determine the difference between unattended and attended AOBP measurements through systematic review and meta-analysis. METHODS: We searched the PubMed and the Cochrane Collaboration Library and we screened the references' list of relevant reports to identify potentially eligible articles. For included studies, quality was assessed by using the Quality Assessment for Diagnostic Accuracy Studies 2. The weighted pooled BP difference with 95% confidence interval (CI) between unattended and attended AOBP was estimated under the random effects model. RESULTS: Twelve studies (1762 subjects) were included. The systolic and diastolic BP difference between unattended and attended AOBP measurements was - 3.66 (- 6.58 to - 0.75) and - 1.67 (- 2.78 to - 0.55) mmHg, respectively. Heterogeneity across studies was high (I2 = 97,1% for systolic and I2 = 89% for diastolic BP, P < 0.001) and was partially determined by the sequence of performing unattended and attended BP measurements, the device used for AOBP, the geographic region in which studies were performed and the presence of a resting period before unattended AOBP. CONCLUSIONS: Due to the high heterogeneity, we cannot rely on the weighted pooled estimate. However, the available evidence suggests that attended AOBP yielded higher systolic and diastolic BP levels and it seems that the procedural methodology determines partially the statistical heterogeneity across studies.

Morning Surge and Peak Morning Ambulatory Blood Pressure Versus Automated Office Blood Pressure in Predicting Cardiovascular Disease.

INTRODUCTION: Automated office blood pressure (AOBP) has been recently shown to predict equally well to ambulatory blood pressure (ABP), conventional office blood pressure (OBP) and home blood pressure (HBP), cardiovascular (CV) events among hypertensives. AIM: To compare AOBP recording and ABP monitoring in order to evaluate morning blood pressure (BP) peak in predicting CV events and deaths in hypertensives. METHODS: We assessed 236 initially untreated hypertensives, examined between 2009 and 2013. The end points were CV and non-CV death and any CV event including myocardial infarction, evidence of coronary heart disease, heart failure hospitalization, severe arrhythmia, stroke, and symptomatic peripheral artery disease. We fitted proportional hazards models using the different modalities as predictors and evaluated their predictive performance using two metrics: the Akaike's Information Criterion, and Harrell's C-index. RESULTS: After a mean follow-up of 7 years, 23 subjects (39% women) had at least one CV event. In Cox regression models, systolic conventional OBP, AOBP and peak morning BP were predictive of CV events (p < 0.05). The Akaike Information Criterion showed smaller values for AOBP than peak morning BP, indicating a better performance in predicting CV events (227.2736 and 238.7413, respectively). The C-index was 0.6563 for systolic AOBP and 0.6243 for peak morning BP indicating a better predicting ability for AOBP. CONCLUSION: In initially untreated hypertensives, AOBP appears to be at least equally reliable to 24-h monitoring in the evaluation of morning BP peak in order to detect CV disease whereas the sleep-trough and preawakening morning BP surge did not indicate such an effect.

Unobserved automated office BP is similar to other clinic BP measurements: A prospective randomized study.

Results of the SPRINT study have been disputed, based on the assumption that unattended BP measurements do not correlate with usual BP measurements. In this study, the authors investigated the correlation of unattended SPRINT-like measurements with other conventional measurements. All BP measurements were taken with the patient seated in a comfortable chair with the legs uncrossed and not speaking during the procedure. For the purpose of this study, sixty-five patients, mostly male (93%), were recruited from our hypertension clinic and all were on antihypertensive medication (av 3.0 ± 1.1). Patients were at high cardiovascular risk with high rates of comorbidities, av age 68 ± 12 years, 49% with diabetes, 34% with mild CKD (CKD 1-3, average eGFR 55.0 ± 13 mL/min/1.73 m2 ), and 20% with history of stable coronary artery disease. All BP measurements were similar with no statistically significant difference (one-way ANOVA, P = 0.621). Compared to unattended SPRINT BP values (139.77 ± 19.22/75.42 ± 11.72 mm Hg), the clinic BP measurements were numerically slightly higher but with a NS P value (P = 0.163). Similarly, unattended BP measurements were similar to values taken by the clinic physician. In a smaller cohort of 11 patients, the authors compared unobserved vs observed SPRINT-like BP measurements, and in 13 patients, the authors compared unobserved SPRINT-like BP measurements to average home BP measurements (Table 3). There were no significant differences between any of the subgroups (one-way ANOVA, P = 0.816 for systolic and P = 0.803 for diastolic). The authors conclude that unattended BP measurements taken (the SPRINT way) are similar to other conventional office blood pressure measurements.

Attended and Unattended Automated Office Blood Pressure Measurements Have Better Agreement With Ambulatory Monitoring Than Conventional Office Readings.

BACKGROUND: Automated office blood pressure (AOBP) measurement is superior to conventional office blood pressure (OBP) because it eliminates the "white coat effect" and shows a strong association with ambulatory blood pressure. METHODS AND RESULTS: We conducted a cross-sectional study in 146 participants with office hypertension, and we compared AOBP readings, taken with or without the presence of study personnel, before and after the conventional office readings to determine whether their variation in blood pressure showed a difference in blood pressure values. We also compared AOBP measurements with daytime ambulatory blood pressure monitoring and conventional office readings. The mean age of the studied population was 56±12 years, and 53.4% of participants were male. Bland-Altman analysis revealed a bias (ie, mean of the differences) of 0.6±6 mm Hg systolic for attended AOBP compared with unattended and 1.4±6 and 0.1±6 mm Hg bias for attended compared with unattended systolic AOBP when measurements were performed before and after conventional readings, respectively. A small bias was observed when unattended and attended systolic AOBP measurements were compared with daytime ambulatory blood pressure monitoring (1.3±13 and 0.6±13 mm Hg, respectively). Biases were higher for conventional OBP readings compared with unattended AOBP (-5.6±15 mm Hg for unattended AOBP and oscillometric OBP measured by a physician, -6.8±14 mm Hg for unattended AOBP and oscillometric OBP measured by a nurse, and -2.1±12 mm Hg for unattended AOBP and auscultatory OBP measured by a second physician). CONCLUSIONS: Our findings showed that independent of the presence or absence of medical staff, AOBP readings revealed similar values that were closer to daytime ambulatory blood pressure monitoring than conventional office readings, further supporting the use of AOBP in the clinical setting.

Hypertension and atrial fibrillation: a bench to bedside perspective.

Atrial Fibrillation (AF) is the most common cardiac arrhythmia in clinical practice and its prevalence increases markedly with advancing age, worldwide. Almost every primary care physician, internist, or cardiologist, has dealt with stroke or with other complications of AF. Still, its management remains a hot issue for clinicians and the debate over which treatment strategy is the best is ongoing. Moreover, AF increases significantly the total cardiovascular (CV) morbidity and mortality. Despite a great bulk of data in the existing medical literature, the pathophysiology of AF in patients with hypertensive heart disease (HHD) is poorly understood, and the underlying signaling pathways linking hypertension (HTN) to AF remain to be fully elucidated. The scope of this article is to discuss the myocardial anatomical and physiological alterations that occur in HTN, and highlight the proposed electrophysiological mechanisms that cause the hypertensive heart to fibrillate. In addition, we will focus on the latest ESC 2016 guidelines for the risk stratification of AF patients as a tool to guide anticoagulation which represents the mainstay of treatment for AF. Last, the other therapeutic approaches for hypertensives with AF currently adopted for optimal patient management will be reviewed.

Home, automated office, and conventional office blood pressure as predictors of cardiovascular risk.

Automated office blood pressure (AOBP) has recently been shown to closely predict cardiovascular (CV) events in the elderly. Home blood pressure (HBP) has also been accepted as a valuable method in the prediction of CV disease. This study aimed to compare conventional office BP (OBP), HBP, and AOBP in order to evaluate their value in predicting CV events and deaths in hypertensives. We assessed 236 initially treatment naïve hypertensives, examined between 2009 and 2013. The end points were any CV and non-CV event including mortality, myocardial infarction, coronary heart disease, hospitalization for heart failure, severe arrhythmia, stroke, and intermittent claudication. We fitted proportional hazards models using the different modalities as predictors and evaluated their predictive performance using three metrics: time-dependent receiver operating characteristics curves, the Akaike's Information Criterion, and Harrell's C-index. After a mean follow-up of 7 years, 23 participants (39% women) had experienced ≥1 CV event. Conventional office systolic (hazard ratio [HR] per 1 mm Hg increase in BP, 1.028; 95% confidence interval [CI], 1.009-1.048), automated office systolic (HR per 1 mm Hg increase in BP, 1.031; 95% CI, 1.008-1.054), and home systolic (HR, 1.025; 95% CI, 1.003-1.047) were predictive of CV events. All systolic BP measurements were predictive after adjustment for other CV risk factors (P < .05). The predictive performance of the different modalities was similar. Conventional OBP was significantly higher than AOBP and average HBP. AOBP predicts equally well to OBP and HBP CV events. It appears to be comparable to HBP in the assessment of CV risk, and therefore, its introduction into guidelines and clinical practice as the reference method for assessing BP in the office seems reasonable after verification of these findings by randomized trials.