Central blood pressure as a risk marker for cardiovascular complications

Ciśnienie tętnicze i kształt fali tętna różnią się w poszczególnych odcinkach drzewa tętniczego. Ciśnienie panujące w aorcie i tętnicy szyjnej, nazywane ciśnieniem centralnym, wydaje się lepiej określać ryzyko powikłań sercowo-naczyniowych nadciśnienia niż wartość mierzona standardową techniką w tętnicy ramiennej. Zmiany ciśnienia centralnego są w znacznej mierzeuwarunkowane postępującym stwardnieniem tętnic. Dane z ostatnich wskazują, że leki hipotensyjne mogą w odmienny sposób wpływać na ciśnienie centralne i obwodowe. Znaczenie tego zjawiska pozostaje przedmiotem toczących się badań klinicznych.Blood pressure differs along the vascular tree. Measurement of briachial artery cuff pressure may not correspond to aortic or carotid artery pressure, so called central pressure, which is better risk predictors for organ complications of hypertension. Central blood pressure is mostly affected by changes in arterial stiffness. Recent data show that despite similar effect on brachial arterial pressure antihypertensive drugs may differently affect central pressure. Ongoing clinical trials include measurement of central pressure to evaluate its significance

Rare Causes of Hypertension

Istnieje kilka postaci nadciśnienia tętniczego, które mimo rzadkiego występowania powinny być uwzględniane w diagnostyce nadciśnienia. W niektórych przypadkach przyczyna nadciśnienia jest potencjalnie usuwalna, w innych -wczesne zastosowanie odpowiedniego leczenia pozwala uniknąć groźnych powikłań. Pierwotny reninizm jest potencjalnie usuwalną przyczyną ciężkiego, wtórnego nadciśnienia tętniczego. U chorych z guzami wywodzącymi się z aparatu przykłębuszkowego nerek wzmożone wytwarzanie reniny prowadzi do zwiększenia sekrecji aldosteronu. Leczeniem z wyboru pierwotnego reninizmu jest operacyjne usunięcie guza, które w większości przypadków powoduje normalizację ciśnienia tętniczego i ustąpienie innych objawów klinicznych. Bardzo rzadką przyczyną nadciśnienia tętniczego jest guz typu hemangioendothelioma wydzielający endotelinę, substancję o wybitnych właściwościach presyjnych. Również rzadkim zespołem, przebiegającym z nadciśnieniem tętniczym występującym rodzinnie, jest zespół Gordona. Charakteryzuje się hiperkaliemią, hiperchloremią i kwasicą, przy prawidłowym przesączaniu kłębuszkowym. Pierwotny hiperaldosteronizm poddający się leczeniu glikokortykoidami (GRA) jest postacią nadciśnienia tętniczego występującą rodzinnie, dziedziczoną autosomalnie dominująco. Podawanie deksametazonu powoduje normalizację ciśnienia krwi oraz zaburzeń metabolicznych.Zespół Liddle'a, określany mianem pseudohiperaldosteronizmu, jest rzadko występującą rodzinnie tubulopatią, dziedziczoną w sposób autosomalny dominujący Zwiększenie retencji wody i wzrost wolemii jest przyczyną nadciśnienia tętniczego. Należy przypuszczać, że w miarę postępu badań, szczególnie w dziedzinie biologii molekularnej, powiększy się nasza wiedza o mechanizmach patogenetycznych niektórych postaci nadciśnienia tętniczego występujących rzadko.There are some forms of hypertension which despite rare occurrence should be included in the diagnosis of hypertension. Some of them have potentially reversible causes. In some cases early and appropriate treatment allow to avoid dangerous complications. Primary reninism is a potentially reversible cause of severe, secondary hypertension. In the patients with the juxtaglomerular cells tumours increased secretion of renin Leads to increased aldosterone secretion. The surgical resection of the tumour is the treatment of choice. Hemangioendothelioma, a tumour secreting endothelin, which is a potent vasoconstrictor, is a very rare cause of hypertension. Gordon's syndrome is a rare hereditary disorder with hypertension, hyperkaliemia, hyperchloremia and acidemia with normal glomerular filtration rate. Severe hyperkaliemia is the most persistent feature of this syndrome. Glucocorticoid-remediable aldosteronism (GRA) is a hereditary, autosomal dominant disease with hypertension. The treatment with dexamethasone normalises blood pressure and metabolic disturbances. Liddle's syndrome, known as pseudohyperaldosteronism is a rare hereditary, autosomal dominant tubulopathy. Hypertension is caused by an increase in fluid retention and hypervolemia. The treatment of choice is a sodium-depleted diet combined with amiloride or triamteren

Influence of short-term simvastatin administration on parameters of autonomic nervous system activity and blood pressure in hypercholesterolemic patients with or without hypertension

Background The beneficial effects of statins are probably not exclusively related to lipid lowering activity. Therefore, we investigated the effect of simvastatin on blood pressure and heart rate variability (HRV), which can be used for studying autonomous nervous system activity. Material and methods In a prospective, placebo-controlled, crossover trial, we studied 9 males and 11 females aged 55.2 ± 9.7 years with hypercholesterolemia (TC > 220 mg/dl), and normal blood pressure or essential hypertension stage 1–2. After 4 weeks of dietary modifications and placebo administration all subjects were given 20 mg of simvastatin for 4 weeks, followed by a placebo for another 4 weeks. Office and 24-h blood pressure (ABPM), the biochemical parameters of neuroendocrine function and HRV were evaluated. Time-domain and frequency-domain variables were studied such as: SDNN, r-MSSD, pNN50, TP, HF, LF and LF/HF ratio. Results All subjects had significant decrease in total and LDL-cholesterol as well as triglycerides. However, four weeks of simvastatin was not associated with a significant change in office or ambulatory blood pressure. Treatment did not affect basal or stimulated plasma levels of catecholamines, aldosterone, cortisol, neuropeptide Y, renin activity. The differences in HRV between groups did not reach statistical significance. No significant correlation between changes in serum lipid levels and change in cardiac autonomic indices was found. Conclusions This short, prospective, cross-over study has not shown significant effects of simvastatin on blood pressure, biochemical parameters of neuroendocrine function and heart rate variability (HRV) parameters in patients with hypercholesterolemia with or without hypertension

Using electronic health records to support clinical trials: a report on stakeholder engagement for EHR4CR

Background. The conduct of clinical trials is increasingly challenging due to greater complexity and governance requirements as well as difficulties with recruitment and retention. Electronic Health Records for Clinical Research (EHR4CR) aims at improving the conduct of trials by using existing routinely collected data, but little is known about stakeholder views on data availability, information governance, and acceptable working practices. Methods. Senior figures in healthcare organisations across Europe were provided with a description of the project and structured interviews were subsequently conducted to elicit their views. Results. 37 structured interviewees in Germany, UK, Switzerland, and France indicated strong support for the proposed EHR4CR platform. All interviewees reported that using the platform for assessing feasibility would enhance the conduct of clinical trials and the majority also felt it would reduce workloads. Interviewees felt the platform could enhance trial recruitment and adverse event reporting but also felt it could raise either ethical or information governance concerns in their country. Conclusions. There was clear support for EHR4CR and a belief that it could reduce workloads and improve the conduct and quality of trials. However data security, privacy, and information governance issues would need to be carefully managed in the development of the platform

The Relationships between Birthweight and Arterial Blood Pressure

Wśród czynników wpływających na powstanie pierwotnego nadciśnienia tętniczego coraz większe zainteresowanie budzą warunki panujące podczas wewnątrzmacicznego rozwoju płodu, których wskaźnikiem jest urodzeniowa masa ciała. W licznych badaniach epidemiologicznych wykazano, że u osób z małą masą urodzeniową częściej dochodzi do nadciśnienia tętniczego w wieku dorosłym. Przyjmuje się, że w powstawaniu tego związku mogą odgrywać rolę następujące czynniki: wrażliwość tkanek na insulinę, aktywność układu współczulnego, funkcja nerek, funkcja układu podwzgórzowo-przysadkowo-nadnerczowego, podatność tętnic. Ten ostatni parametr był przedmiotem badania przeprowadzonego w Klinice Chorób Wewnętrznych i Nadciśnienia Tętniczego w Akademii Medycznej w Warszawie. Wśród przebadanych 119 zdrowych osób w wieku 19-24 lat nie znaleziono istotnej zależności pomiędzy urodzeniową masą ciała a podatnością dużych naczyń tętniczych.Low birthweight has been associated with increased prevalence of essential hypertension in adulthood. Numerous hypotheses tried to explain this association pointing into insulin resistance, activation of adrenergic system, disturbances of renal and adrenal function as potential mechanisms. Elastin - a major component which determines arterial wall elastic properties, is synthesized mostly during intrauterine period, and low birthweight may be associated with diminished compliance of arteries leading to increased blood pressure. We have investigated the relationship between birthweight and elastic properties of large arteries in 119 normotensive, healthy volunteers aged 19-23. However, in our data there seems to be no relationship between birthweight and elasticity of large arteries in adulthood

Using electronic health records to support clinical trials : a report on stakeholder engagement for EHR4CR

The research leading to these results has received support from the Innovative Medicines Initiative Joint Undertaking under grant agreement number 115189, resources of which are composed of financial contribution from the European Union’s Seventh Framework Programme (FP7/2007–2013) and EFPIA companies’ in kind contribution.BACKGROUND: The conduct of clinical trials is increasingly challenging due to greater complexity and governance requirements as well as difficulties with recruitment and retention. Electronic Health Records for Clinical Research (EHR4CR) aims at improving the conduct of trials by using existing routinely collected data, but little is known about stakeholder views on data availability, information governance, and acceptable working practices. METHODS: Senior figures in healthcare organisations across Europe were provided with a description of the project and structured interviews were subsequently conducted to elicit their views. RESULTS: 37 structured interviewees in Germany, UK, Switzerland, and France indicated strong support for the proposed EHR4CR platform. All interviewees reported that using the platform for assessing feasibility would enhance the conduct of clinical trials and the majority also felt it would reduce workloads. Interviewees felt the platform could enhance trial recruitment and adverse event reporting but also felt it could raise either ethical or information governance concerns in their country. CONCLUSIONS: There was clear support for EHR4CR and a belief that it could reduce workloads and improve the conduct and quality of trials. However data security, privacy, and information governance issues would need to be carefully managed in the development of the platform.Publisher PDFPeer reviewe

Abdominal aortic aneurysm influences the indices of arterial stiffness recorded by pulse wave analysis

Background: Abdominal aortic aneurysm (AAA), forming a blood reservoir alters the geometry of the aorta, which along with increased stiffness of the aortic wall modifies central blood pressure wave, especially the reflected wave. The aim of the study was to compare indices of arterial stiffness recorded by pulse wave analysis (PWA) between patients with AAA and controls. Material and methods: Sixty-nine patients (from 75 originally included) with asymptomatic AAA and 69 (from 74) age-, sex- and body mass index (BMI)-matching patients as a control group were analysed. The following variables of PWA recorded by applanation tonometry were evaluated: central pulse pressure (CPP), central systolic (CSBP) and diastolic (CDBP) blood pressure, central augmentation index (CAIx), the time from the beginning of a pulse wave to: the first systolic peak (CT1), to the beginning of the reflected wave (CT1R) and to the second systolic peak pressure (CT2). Results: Patients with AAA had higher CAIx [33% (12) vs. 28% (20); p < 0.001] than in the control group, lower CPP [36 mm Hg (10) vs. 45 mm Hg (24); p < 0.001), higher CDBP [79 mm Hg (14) vs. 73 mm Hg (13); p = 0.017) and no significant difference in CSBP [115 mm Hg (15) vs. 119 mm Hg (23); NS). Shorter CT1 [102 ms (9) vs. 106 ms (12); p = 0.004) and CT1R [133 ms (11) vs. 138 ms (13.5); p = 0.04) and longer CT2 (232 ms (36) vs. 217 ms (35); p = 0.007) were observed in patients with AAA. Data are presented as median with interquartile range. Conclusion: Differences of central blood pressure variables suggest increased arterial stiffness in patients with AAA. Despite lower values of pulse pressure, overall pressure load of the returning wave is higher, which affect the afterload of the heart

RET Proto-Oncogene Germline Mutation in Pheochromocytoma Patients - Incidence and Clinical Consequences

Wstęp Dotychczasowe badania wskazują, że częstość zespołu mnogiej gruczolakowatości (MEN 2), w skład którego wchodzi guz chromochłonny, jest większa niż dotychczas sądzono. Zespół ten dziedziczony jest w sposób autosomalny dominujący i wywołuje go mutacja protoonkogenu RET. Celem pracy jest ocena częstości występowania oraz kliniczne znaczenie mutacji protoonkogenu RET u chorych z guzem chromochłonnym. Materiał i metody Badania genetyczne w kierunku mutacji protoonkogenu RET przeprowadzono u 106 chorych (średni wiek: 49 ± 14,1 roku, 26M, 80K) z rozpoznanym i potwierdzonym histopatologicznie guzem chromochłonnym. Pacjenci ci byli uprzednio hospitalizowani i leczeni w Klinice Chorób Wewnętrznych i Nadciśnienia Tętniczego Akademii Medycznej w Warszawie w latach 1957–1998 oraz w Klinice Nadciśnienia Tętniczego Instytutu Kardiologii w Warszawie od roku 1980 do 2001. Oceniano również stężenie kalcytoniny (CT), zarówno w warunkach podstawowych, jak i po stymulacji pentagastryną, oraz stężenie parathormonu. Wyniki Obecność mutacji protoonkogenu RET wykazano u 8 chorych (7,4%) - w eksonie 11, w kodonie 634, TGC na CGC u 5 chorych, u pozostałych 3 odpowiednio - w eksonie 11, kodonie 634, TGC na GGC, w eksonie 11, kodonie 634, TGC na TGG oraz w eksonie 13, kodonie 791, TAT na CGC. Nadczynność komórek C potwierdzoną dodatnim testem pentagastrynowym stwierdzono u 5 nosicieli, u 2 chorych wynik testu był wątpliwy, jedynie u 1 chorego stężenie kalcytoniny było prawidłowe. Prawidłowe stężenie CT obserwowano u chorego z mutacją w eksonie 13, kodonie 791, TAT na CGC. U 4 nosicieli potwierdzono histopatologicznie obecność raka rdzeniastego tarczycy (biopsja cienkoigłowa). U 3 chorych wykonano totalną tyroidektomię, dwóch nie wyraziło zgody na dalsze leczenie (w tym jeden z pozytywnym wynikiem biopsji). Pozostali chorzy zostali poinformowani o konieczności totalnej tyroidektomii. U żadnego nosiciela nie stwierdzono nadczynności przytarczyc. Wnioski Wyniki badań autorów potwierdzają doniesienia o konieczności poddawania przesiewowym badaniom genetycznym oceniającym obecność mutacji protoonkogenu RET pacjentów z guzem chromochłonnym. Potwierdzenie nosicielstwa tej mutacji stanowi wskazanie do wykonania totalnej tyroidektomii. Genetyczne badania przesiewowe mogą mieć również znaczenie w wykrywaniu zespołu MEN 2 oraz ustaleniu dalszego postępowania u członków rodzin, u których stwierdza się mutację protoonkogenu RET.Background In patients with pheochromocytoma there may exist more often than expected the autosomal dominant cancer syndrome — multiple endocrine neoplasia type 2 (MEN 2). The susceptibility gene for MEN 2 is the RET proto-oncogene. Germline mutations can be identified by analysis of exons 10, 11, 13–16 of the RET gene. The aim of the study was to evaluate the frequency of these mutations in patients with pheochromocytoma and to report on the conclusions which patients and physicians have drawn. Material and methods We screened for germline mutations in the RET proto-oncogene and clinically evaluated 106 unselected patients with pheochromocytoma (mean age: 49 ± 14,1 years, 26 male, 80 female) histopathologically confirmed, diagnosed and treated in the years 1957–1998 in the Department of Internal Medicine and Hypertension, Warsaw School of Medicine and in the years 1980/81–2001 in the Department of Hypertension, Institute of Cardiology, Warsaw. Determination of calcitonin concentration (CT) was performed in basal conditions and after pentagastrin stimulation; parathormone level was also determined. Results Genetic testing revealed germline mutations in the RET proto-oncogene in 8 patients (7,4%). Carriers had mutation of exon 11, codon 634: TGC to CGC (5 patients), exon 11, codon 634: TGC to GGC (1 patient), exon 11, codon 634: TGC to TGG (1 patient) and in exon 13, codon 791: TAT to TTT (1 patient). Hyperactivity of thyroid C-cells was found in 5 carriers, borderline values of basal and after pentagastrin CT were found in 2 carriers and in only one patient CT concentration was normal. In four patients with RET proto-oncogene mutations, MTC was confirmed histopathologically in fine-needle biopsy. In three of them total thyroidectomy was performed. Two patients refused to be surgically treated (one with positive result of biopsy); the next three RET proto-oncogene germline mutation carriers have been informed that prophylactic total thyroidectomy should be considered. In none of the carriers hyperparathyroidism was observed. Conclusions Our study indicates that patients with pheochromocytoma should be genetically screened for mutations of the RET proto-oncogene. The carriers of these mutations should undergo thyroidectomy. In addition, genetic studies can be useful for the screening of the carriers families

Klinička praksa temeljena na dokazima: pregled prijetnji valjanosti dokaza i kako ih spriječiti

Using the best quality of clinical research evidence is essential for choosing the right treatment for patients. How to identify the best research evidence is, however, difficult. In this narrative review we summarise these threats and describe how to minimise them. Pertinent literature was considered through literature searches combined with personal files. Treatments should generally not be chosen based only on evidence from observational studies or single randomised clinical trials. Systematic reviews with meta-analysis of all identifiable randomised clinical trials with Grading of Recommendations Assessment, Development and Evaluation (GRADE) assessment represent the highest level of evidence. Even though systematic reviews are trust worthier than other types of evidence, all levels of the evidence hierarchy are under threats from systematic errors (bias); design errors (abuse of surrogate outcomes, composite outcomes, etc.); and random errors (play of chance). Clinical research infrastructures may help in providing larger and better conducted trials. Trial Sequential Analysis may help in deciding when there is sufficient evidence in meta-analyses. If threats to the validity of clinical research are carefully considered and minimised, research results will be more valid and this will benefit patients and heath care systems.Primjena najkvalitetnijih dokaza kliničkih istraživanja ključna je u odabiru ispravnog liječenja pacijenata. No, način na koji će se odabrati najbolji dokazi predstavlja često poteškoću. Ovim preglednim člankom prikazujemo opasnosti navedenog odabira, kao i načine kako ih umanjiti. Relevantni izvori razmatrani su pretragom literature u kombinaciji s osobnim datotekama. Izbor liječenja uglavnom se ne bi smio temeljiti isključivo na opservacijskim ili pojedinačnim randomiziranim kliničkim studijama. Sustavni pregledi s metaanalizom svih identificiranih randomiziranih kliničkih studija procijenjenih sustavom stupnjevanja procjene, razvoja i evaluacije preporuka (engl. Grading of Recommendations Assessment, Development and Evaluation; GRADE) predstavljaju najvišu razinu dokaza. Iako su sustavni pregledi pouzdaniji od drugih vrsta dokaza, sve razine hijerarhije dokaza ugrožene su sustavnim pogreškama (engl. bias); pogreškama dizajna studije (zloupotreba surogatnih ishoda, složenih ishoda itd.) i slučajnim pogreškama (igra slučaja). Kliničke istraživačke infrastrukture mogu pomoći u pružanju većih i adekvatnije provedenih ispitivanja. Sekvencijska analiza studija može pomoći pri odlučivanju kada postoji dovoljna razina dokaza u metaanalizama. Ako se prijetnje valjanosti kliničkih istraživanja pažljivo razmatraju i minimiziraju, rezultati istraživanja bit će vrjedniji i korisniji pacientima i zdravstvenim sustavima