Nontraditional systems in aging research: an update.

Research on the evolutionary and mechanistic aspects of aging and longevity has a reductionist nature, as the majority of knowledge originates from experiments on a relatively small number of systems and species. Good examples are the studies on the cellular, molecular, and genetic attributes of aging (senescence) that are primarily based on a narrow group of somatic cells, especially fibroblasts. Research on aging and/or longevity at the organismal level is dominated, in turn, by experiments on Drosophila melanogaster, worms (Caenorhabditis elegans), yeast (Saccharomyces cerevisiae), and higher organisms such as mice and humans. Other systems of aging, though numerous, constitute the minority. In this review, we collected and discussed a plethora of up-to-date findings about studies of aging, longevity, and sometimes even immortality in several valuable but less frequently used systems, including bacteria (Caulobacter crescentus, Escherichia coli), invertebrates (Turritopsis dohrnii, Hydra sp., Arctica islandica), fishes (Nothobranchius sp., Greenland shark), reptiles (giant tortoise), mammals (blind mole rats, naked mole rats, bats, elephants, killer whale), and even 3D organoids, to prove that they offer biogerontologists as much as the more conventional tools. At the same time, the diversified knowledge gained owing to research on those species may help to reconsider aging from a broader perspective, which should translate into a better understanding of this tremendously complex and clearly system-specific phenomenon.

Visceral fat level correction of the left ventricular hypertrophy electrocardiographic criteria.

BACKGROUND: Left ventricular hypertrophy (LVH) is a well-known risk factor for cardiovascular events. Even though there are many electrocardiographic (ECG) criteria for LVH, they still provide poor performance, especially among obese patients. The aim of this study was to examine whether adding visceral fat to ECG LVH criteria improves accuracy in the diagnosis. METHODS: One thousand seven hundred twenty two patients were included in the study. All patients underwent a complete physical examination, office blood pressure measurement, analysis of body composition, 12-lead ECG, and M-mode two-dimensional echocardiography. Four standard ECG criteria for LVH were analyzed, including Cornell voltage criteria, Cornell duration criteria, Sokolow-Lyon voltage criteria, and Sokolow-Lyon product criteria. Adjustments of ECG LVH criteria were performed using visceral fat level (VFATL) and BMI. Transthoracic echocardiography was used as a reference method to compare the quality of ECG LVH criteria. RESULTS: Multivariate logistic regression models were created and revealed a significant increase of area under curve (AUC) after VFATL and BMI addition to ECG LVH criteria. Improvement of sensitivity at 90% specificity was observed in all created models. The odds ratio (OR) of the analyzed ECG criteria increased after adding VFATL and BMI to the models. Furthermore, ROC curves analysis exposed better characteristics in detecting LVH of VFATL-adjusted criteria than BMI-adjusted and unadjusted criteria. CONCLUSIONS: Adjusting ECG indexes to BMI or VFATL improves the sensitivity of LVH detection. VFATL-corrected indexes are more sufficiently than BMI-corrected. After advancements in indexes, both lean and morbidly obese individuals outcomes show a greater prevalence of correct LVH diagnosis.

[Treatment of arterial hypertension in pregnancy in relation to current guidelines of the Polish Society of Arterial Hypertension from 2011]. / Leczenie nadcisnienia tetniczego w ciazy w swietle aktualnych wytycznych Polskiego Towarzystwa Nadcisnienia Tetniczego z 2011 roku.

Arterial hypertension concerns 7-10% of pregnancies and leads to an increased risk of complications for both, the mother and the child. This rate will probably rise in the years to come due to the notable tendency among women to delay the decision to become pregnant - values of blood pressure and occurrence of arterial hypertension increase with age, as well as due to the growing problem of obesity resulting from inappropriate dietary habits and lack of regular everyday physical activity. Difficulties with management of that clinical condition are partly related with lack of unified and widely accepted guidelines. Different opinions in the subject of terminology and classification of pregnancy hypertension or indications for pharmacotherapy as well as choice of the optimal antihypertensive drug, emerge from objective causes such as combination of various pathogenetic factors typical for arterial hypertension itself and those connected with pregnancy elsewhere stressed priorities of therapy from the point of view of the health of the mother and of the fetus, as well as lack of randomized clinical trials due to obvious ethical purposes, but also from the fact that pregnancy hypertension is a focus of attention for different specialists - obstetricians, hypertensiologists and perinatologists. A good cooperation regarding experience and information among all of these specializations would be the most beneficial for pregnant women and their children. Lack of new modern antihypertensive agents, safe and effective in pregnancy while the older ones are being withdrawn from the market as their production is no longer cost-effective for pharmacological companies, has become an increasing problem in many countries, and Poland among them. The aim of the following publication was to present the statement on management of pregnancy hypertension from the current guidelines of the Polish Society of Arterial Hypertension 2011 to gynecologists and obstetricians, with a commentary According to the guidelines, methyldopa, labetalol (or metoprolol), long-acting nifedipine or verapamil should be used in the therapy of mild and moderate pregnancy hypertension, preferably in the given order In case of severe and life-threatening arterial hypertension, labetalol intravenously should be administered and if it is still not sufficient, eventually sodium nitroprusside or hydralazine could be ordered, bearing in mind their possible adverse effects. Unfortunately labetalol, nifedipine, hydralazine and sodium nitroprusside are no longer available in Poland, which significantly narrows the practical treatment possibilities in the pregnant population. Inhibitors of angiotensin converting enzyme and angiotensin II receptor blockers are contraindicated during pregnancy and breastfeeding, as well as aldosteron inhibitors, as suggest in the guidelines. In the paper the authors present the guidelines and also, based on the information available to date in medical journals, other hypertension pharmacotherapeutic options possible for consideration in pregnancy which could be helpful in management of severe arterial hypertension in pregnancy.

Parameters of arterial function and structure in adult patients after coarctation repair.

Regardless of a successful operation, patients with coarctation of aorta (CoAo) are exposed to the risk of hypertension and a propensity to vascular and end-organ damage. The aim of this study is to evaluate the influence of residual aorta stenosis as well as the age at the operation on the parameters of arterial function and structure in patients after CoAo repair. Eighty-five patients after CoAo repair (53 males; mean age: 34.6 ± 10.3 years, mean age at the repair: 10.9 ± 8.2 years) were enrolled in the study. The control group consisted of 30 healthy subjects (18 males; mean age: 33.6 ± 8.2 years). Indices of systemic arterial remodeling [flow-mediated dilatation (FMD), nitroglycerine-mediated vasodilatation (NMD), carotid intima-media thickness (IMT), pulse wave velocity (PWV)] were analyzed in all study patients. In normotensive patients after CoAo repair (47/55%), a significantly increased PWV was observed in comparison to the control group (6.8 ± 1.2 vs. 5.4 ± 0.9 m/s; p = 0.003), with no difference in IMT values (0.53 ± 0.1 vs. 0.51 ± 0.1 mm; p = 0.06). Mean FMD (4.8 ± 2.8 vs. 8.5 ± 2.3%; p = 0.00003) and NMD (11.3 ± 4.6 vs. 19.8 ± 7.2%; p = 0.00001) were lower than in the controls. In patients with a residual aorta stenosis (46/54%), defined as an arm-leg pressure gradient ≥ 20 mmHg, no differences were found within the scope of both systolic and diastolic blood pressure and of all of the examined vascular parameters. No significant correlations were revealed between the vascular parameters and the gradient across descending aorta as well as the age at the operation. Residual stenosis in the descending aorta does not affect the arterial vasodilatation nor stiffness in patients after CoAo repair. An early surgery does not influence the remodeling of the vessels, which supports the thesis that CoAo is a generalized vascular disease and that even an early operation cannot prevent the progressive and vascular changes and end-organ damage.

The Effects of Eplerenone on the Circadian Blood Pressure Pattern and Left Ventricular Hypertrophy in Patients with Obstructive Sleep Apnea and Resistant Hypertension-A Randomized, Controlled Trial.

The obstructive sleep apnea (OSA) is highly associated with various significant cardiovascular outcomes such as resistant hypertension (RAH). Despite this, as of now the relationship between high night-time blood pressure (BP) and left ventricular hypertrophy (LVH) in patients with OSA and RAH is not fully understood. The aim of this study was to assess the influence of the addition of eplerenone to a standard antihypertensive therapy on parameters of 24-h ambulatory blood pressure measurement (ABPM) as well as on the results of echocardiography and polysomnography in patients with OSA and RAH. The patients were randomly assigned to one of the two study groups: the treatment group, receiving 50 mg/d eplerenone orally for 6 months (n = 51) and the control group, remaining on their standard antihypertensive therapy (n = 51). After that period, a significant reduction in the night-time BP parameters in the treatment group including an increased night blood pressure fall from 4.6 to 8.9% was noted. Additionally, the number of non-dipper patients was reduced by 45.1%. The treatment group also revealed a decrease in left ventricular hypertrophy and in the apnea-hypopnea index (AHI) with a positive correlation being observed between these two parameters. This study is the first to report the improvement of the circadian BP profile and the improvement of the left ventricle geometry in patients with OSA and RAH following the addition of selective mineralocorticoid receptor antagonists to antihypertensive therapy.

Prevalence of dyslipidemia and general ineffectiveness of its treatment in both primary and secondary prevention of coronary heart disease within family medicine framework--results of LIPIDOGRAM 2005--a nationwide epidemiological study. Dyslipidemia in Poland--ineffective treatment.

PURPOSE: Despite major advances in cardiology dyslipidemia continues to be underdiagnosed and undertreated. The study aimed to evaluate current prevalence of dyslipidemia and treatment efficacy in both coronary and non-coronary subjects. METHODS: 17,065 subjects aged 30-95 years (20.51%--coronary heart disease (CHD) patients), seeking medical help for disparate reasons from 675 family physicians, were randomly enrolled. Family physicians completed pertinent questionnaires against available medical records and measured patients' lipid levels during a single appointment. RESULTS: Dyslipidemia was detected in 73% of the CHD subjects vs. 46% of the non-CHD ones (p = 0.00001); its severity differing regionally. Hypolipemic treatment was administered to 82% of the CHD subjects vs. 12% of the non-CHD ones (p = 0.00001). Mean concentrations of LDL-cholesterol were higher in the treated subjects (p = 0.00002). Only 10% of the CHD subjects and 20% of the non-CHD ones were treated effectively for dyslipidemiae. CONCLUSIONS: Dyslipidemia was found widely prevalent nationwide, as well as poorly pharmacologically controlled in both primary and secondary prevention. Diversity of economic factors notwithstanding, this was mainly attributable to ineffective patient educational policies, meriting therefore immediate expansion and enhancement of existing disease management system in terms of adequate monitoring and effective treatment of key coronary risk factors.

Arterial stiffness and arterial function in adult cyanotic patients with congenital heart disease.

BACKGROUND: Mortality in cyanotic patients with congenital heart diseases (CHD) is high, mainly due to cardiovascular complications. It is known that endothelial dysfunction, increased arterial stiffness, and impaired vascular function have negative influence on cardiovascular prognosis. The aim of the study was to assess parameters of arterial stiffness and vascular dysfunction in cyanotic patients with CHD as well as their potential relation to impaired blood oxygen saturation and polycythemia parameters typical for cyanosis. METHODS: A total of 36 CHD cyanotic patients (17 males) (42.3±16.3 years) and 35 healthy individuals (16 males) (39.6±10.4 years) were enrolled. Assessed parameters were intima media thickness and flow-mediated dilatation (FMD). Assessed parameters using applanation tonometry methods were aortic systolic pressure, aortic pulse pressure (AoPP), augmentation pressure (AP), augmentation index (AI), pulse pressure amplification (PPampl), and pulse wave velocity (PWV). RESULTS: AoPP (37.3±11.1mmHg vs. 29±6.5mmHg; p=0.002), AP (10.1±7.3mmHg vs. 1.1±3.9mmHg; p=0.00001), AI (24.7±13.5% vs. 3.0±13.6%; p=0.00001), and PWV (7.4±2.1m/s vs. 6.3±0.7m/s; p=0.003) were higher, and PPampl was lower (135.3±16.1% vs. 160.4±12.8%; p=0.00001) in the studied group compared to controls and proved the presence of the increased stiffness of arteries. Impairment of FMD was observed (9.0±5.6 vs. 10.9±4.7; p=0.04). No significant correlations were found between analyzed arterial parameters and biochemical ones characterizing cyanotic patients depicting rheological properties of blood. CONCLUSIONS: Cyanotic patients with CHD are characterized by increased arterial stiffness estimated with pulse wave analysis parameters and by deteriorated arterial function expressed with worse vasodilatative response in comparison with healthy population. It may confirm relevance of those mechanisms in development of increased rate of cardiovascular events in this population. Association between oxygen saturation or polycythemia and arterial stiffening or vascular dysfunction was not found in these patients.

Difference between central and peripheral blood pressure in healthy and hypertension-complicated pregnancy.

OBJECTIVE: Hemodynamics of a pregnant woman differ and change over time depending on the age of gestation. In the general population, brachial-aortic systolic pressure (SBP-AoSP) difference is known and discussed, whereas in pregnancy, it is not established. On the basis of theoretical premises it is probably different and changes with time of gestation. As AoSP is more relevant for internal organs, also for placental perfusion, and still not widely available in clinical practice, knowledge of the average SBP-AoSP difference in a healthy and complicated pregnancy could be of additional value for the management of pregnancy hypertension. The aim of this study was to assess the SBP-AoSP difference in healthy and hypertensive pregnancies in comparison with nonpregnant controls. PARTICIPANTS AND METHODS: Aortic blood pressure with applanation tonometry and brachial blood pressure under standardized conditions were measured monthly and once postpartum in 36 normotensive pregnant women (age: 29.6±4.8 years) and compared with 25 hypertensive pregnancies (age: 30.5±5.4 years) before antihypertensive treatment implementation and with 25 nonpregnant controls (age: 30.2±5.5 years). RESULTS: In hypertensive pregnancies, the SBP-AoSP difference was smaller throughout the entire pregnancy than in healthy pregnancies (in the second and third trimester: 14.44 vs. 15.7 mmHg, P=0.002, and 12.9 vs. 14 mmHg, P=0.02), and smaller than that in nonpregnant controls (14.88 mmHg, for third trimester, P=0.036). Comparison of healthy pregnancy and controls showed an insignificant increase in SBP-AoSP difference in the first and second trimester, whereas in the third trimester, because of a larger increase of AoSP, the SBP-AoSP difference was smaller than that in nonpregnant controls (14.66 mmHg, P>0.05). CONCLUSION: A reduced SBP-AoSP difference was found in hypertensive pregnancies compared with healthy controls, which may signify a narrower safety margin for complications. Comparison of pregnant women with nonpregnant controls showed that a significant difference for the SBP-AoSP difference was present only for the postpartum period.

Assessment of coagulation profile by thromboelastometry in adult patients with cyanotic congenital heart disease.

BACKGROUND: Patients with cyanotic congenital heart disease (CCHD) have an increased risk of bleeding and thrombotic complications. Prolonged conventional coagulation screening parameters, such as activated partial thromboplastin time or prothrombin time, are reported in less than 20% of CCHD patients. METHODS: The aim of this study was to determine the haemostatic abnormalities in 32 adult patients with CCHD by rotation thromboelastometry (ROTEM) with assessment of coagulation dynamic properties, as a guide for perioperative prophylaxis or haemostatic therapy. The control group consisted of 35 healthy subjects. RESULTS: Our results suggest that CCHD patients, in comparison to healthy controls, had a tendency to hypocoagulate with delayed activation of haemostasis and clot formation, initiated by both intrinsic and extrinsic activators. The growth of the clot was slower and the clot firmness was decreased, which may additionally contribute to bleeding diathesis. Moreover, the clot lysis readings suggest higher clot stability in the CCHD group. All velocity parameters were markedly lower in the CCHD patients, indicating a decreased rate of clot formation. Although coagulation tests and platelet count were normal, the usefulness of rotation thromboelastometry in monitoring or guiding therapy in CCHD patients is demonstrated. CONCLUSION: In conclusion, our results provide new insights into the data on hypocoagulation with impaired clot lysis in adult CCHD patients as determined by ROTEM. Our findings may assist in determining the optimal management of patients with CCHD undergoing surgery.

Effect of eplerenone on the severity of obstructive sleep apnea and arterial stiffness in patients with resistant arterial hypertension.

INTRODUCTION    Obstructive sleep apnea (OSA) is considered to be one of the major causes of resistant arterial hypertension (RAH). Apnea episodes cause hypoxia, which triggers the activation of the renin-angiotensin-aldosterone system. This leads to water retention and swelling in the neck region, exacerbating OSA symptoms. It is assumed that the use of eplerenone may reduce the swelling and thus alleviate the severity of OSA. OBJECTIVES    We aimed to prospectively assess the impact of eplerenone on the severity of OSA and arterial stiffness in patients with RAH. PATIENTS AND METHODS    The study included 31 patients with RAH and OSA. The exclusion criteria were as follows: secondary hypertension, myocardial infarction, stroke 6 months prior to the study, congestive heart failure, chronic kidney failure, alcohol or drug addiction, and active cancer. In all patients, the following tests were performed: blood pressure (BP) measurement (traditionally and using ambulatory BP measuring [ABPM]), applanation tonometry, polysomnography, and the apnea-hypopnea index (AHI) calculation. The tests were done before and after 3 months of eplerenone therapy. Patients received 50 mg of oral eplerenone daily, along with other hypertensive drugs. RESULTS    The mean age of participants was 57.76 ±6.16 years. After 3 months of eplerenone therapy, we observed a significant reduction in the AHI, neck circumference, BP, aortic pulse wave, and arterial wall stiffness. There were significant correlations between the AHI and mean BP measured by ABPM and between the AHI and arterial stiffness parameters. CONCLUSIONS    Our results provide evidence for the clinical significance of eplerenone, not only as an antihypertensive medication but also as a drug that may reduce the severity of OSA and arterial stiffness in patients with RAH and OSA.

Asymmetric dimethylarginine and vascular indices of atherosclerosis in patients after coarctation of aorta repair.

OBJECTIVE: Cardiovascular events are the main cause of premature death after successful repair of aortic coarctation (CoA). The aim of this study was to assess the selected biochemical markers of atherosclerosis in normotensive CoA repaired patients and to establish its relation to ultrasound indexes of vascular pathology. METHODS: 62 patients after CoA repair (37 males, age: 34.1 ± 1.4 yrs) and 20 control individuals (10 males, age: 34.8 ± 2.2 yrs) were enrolled in the study. The serum markers: asymmetric dimethylarginine (ADMA), nitrites/nitrates (NOx), high-sensitivity C-reactive protein (hsCRP), and following vascular parameters: flow-mediated dilatation (FMD), intima-media thickness (IMT) and pulse wave velocity (PWV) were analyzed. RESULTS: 33 CoA repaired patients were normotensive, and compared to controls, they presented higher serum ADMA concentrations (0.59 ± 0.04 umol/l vs. 0.46 ± 0.03 umol/l, p=0.035). An analysis of the vascular parameters revealed decreased FMD (4.75 ± 0.5%), NMD (11.86 ± 0.8%) and increased PWV (6.90 ± 0.2 m/s) values in the normotensive patients as compared with the control group (FMD: 8.6 ± 0.9%, p<0.001, NMD: 20.94 ± 1.7%, p<0.001; PWV: 5.49 ± 0.2, p=0.023). There were no differences in the serum levels of NOx, hsCRP as well as IMT values between normotensive patients and the control group. A multivariate regression analysis revealed that serum ADMA level was a factor independently associated with the FMD value (r=-0.334; p=0.031) in normotensive CoA repaired group. CONCLUSIONS: Early biochemical and vascular indices of atherosclerosis such as increased serum ADMA concentration as well as impaired vasodilatation and increased arterial stiffness are observed in patients after CoA repair. Serum ADMA is a strong predictor of endothelial dysfunction in patients with CoA repair.

Augmentation of central arterial pressure in adult patients after coarctation repair.

OBJECTIVES: Arterial hypertension and its complications are associated with an increased morbidity and mortality in patients after aortic coarctation (CoA) repair. It is debatable whether early surgery can prevent it. Residual stenosis of descending aorta (AoD) and stiffness in the precoarctation region supposedly lead to hypertension. The aim of this study was to evaluate aortic pulse-wave parameters in adult patients after CoA repair and to determine the influence of residual stenosis and age at operation on their values. METHODS: Eighty-five patients underwent CoA repair (53 males; aged 34.6±10.3 years, age at operation: 10.9±8.2 years). The control group consisted of 30 individuals (18 males; aged 33.6±8.2 years). Augmentation pressure (AP), augmentation index (AI), aortic pulse pressure (APP), and pulse-wave velocity (PWV) were measured with applanation tonometry method. RESULTS: Normotensive patients after CoA repair (47/55%) had higher values of AP (7.3±4.6 vs. 4.4±3.6 mmHg; P=0.002), AI (18.6±10.4 vs. 13.5±4.3%; P=0.03), APP (39.6±8.8 vs. 35.1±9.8; P=0.00001), and PWV (6.8±1.2 vs. 5.4±0.9 m/s; P=0.003) than controls. Forty-six patients presented signs of recoarctation. No significant differences in the systolic blood pressure and diastolic blood pressure, AI and PWV were found between AoD(+) and AoD(-) but AoD(+) had significantly higher APP (46.7±13.8 vs. 38.3±6.9; P=0.001) and AP (10.5±6.9 vs. 7.5±4.1; P=0.02). Significant correlations were found between current age and APP, AP, and AI. No significant correlations were found between central parameters and the age at operation. CONCLUSION: Normotensive patients after CoA repair have elevated central parameters, related to the residual AoD gradient, regardless of the age at operation. Even early repair cannot prevent progressive vascular impairment in CoA.

Vascular remodeling in adults after coarctation repair: impact of descending aorta stenosis and age at surgery.

BACKGROUND: Patients after successful repair of coarctation of aorta (CoAo) are at risk of hypertension at rest and associated end-organ damage. The aim of the study was to assess arterial stiffness and function in adults after coarctation repair in relation to descending aorta (AoD) residual coarctation and patient's age at operation. METHODS: 85 patients after CoAo repair (53 males) aged 34.6 ± 10.3 years; median age at operation 0.9 ± 8.2 years. The control group-30 individuals (18 males) at mean age 33.6 ± 8.2 years. The following central parameters: augmentation pressure (AP) and augmentation index (AI) as well as peripheral vascular parameters: flow-mediated dilatation (FMD), nitroglycerin-mediated vasodilatation (NMD), intima-media thickness (IMT) and pulse wave velocity (PWV) were measured. RESULTS: 47 CoAo-repaired patients were normotensive, and compared to control, they presented higher values of central parameters AP (7.3 ± 4.6 vs. 4.4 ± 3.6 mmHg; p = 0.002) and AI (18.6 ± 10.4 vs. 13.5 ± 4.3%; p = 0.03); as well as the increased PWV (6.8 ± 1.2 vs. 5.4 ± 0.9 m/s; p = 0.003), while IMT was comparable (0.53 ± 0.01 vs. 0.51 ± 0.01 mm; p = 0.06). The vasodilatation was impaired in the normotensive patients: FMD (4.8 ± 2.8 vs. 8.5 ± 2.3%; p = 0.00003) and NMD (11.3 ± 4.6 vs. 19.8 ± 7.2%; p = 0.00001). The comparison of recoarctation (46, 54%) to non-recoarctation (39, 46%) patients did not reveal any significant differences in resting systolic and diastolic pressures, as well as the values of AI and the peripheral vascular parameters; the value of AP was higher in the recoarctation patients (10.5 ± 6.9 vs. 7.5 ± 4.1; p = 0.02) and correlated positively with the gradient across AoD (r = 0.295, p = 0.01). There was no significant linear correlation between age at the time of surgery and any of peripheral arterial parameters. CONCLUSIONS: Residual stenosis in AoD does not affect the arterial vasodilatation nor stiffness in patients after CoAo repair. Early operation has no impact on peripheral vascular remodeling or central pressure which supports the claim that coarctation of the aorta is a systemic vascular disorder which leads to progressive vascular and end-organ damage despite early correction.