scholarly journals Pathogenetic role of cell-free circulating mitochondrial DNA in blood in the development of arterial hypertension

Author(s):  
С.А. Лепехова ◽  
Е.А. Трофимова ◽  
С.В. Кирильчик ◽  
В.В. Киреева ◽  
Ю.К. Усольцев ◽  
...  

Изучение свободно циркулирующей митохондриальной ДНК (мтДНК) плазмы крови вызывает растущий интерес. Предполагается, что показатель мтДНК может быть перспективным клиническим биомаркёром оценки рисков течения заболеваний. Целью исследования явилась оценка взаимосвязи количественного показателя мтДНК со стадией заболевания и сердечно-сосудистым риском у пациентов с артериальной гипертензией (АГ). Методы. В исследовании участвовал 70 пациентов, которые были разделены на группу с АГ (n = 51) и контрольную группу практически здоровых пациентов (n = 19). Все пациенты подписали информированное согласие на обследование и обработку данных в рамках научного исследования. Проведена оценка демографических данных, длительности заболевания АГ, факторов риска, наследственности, уровня физической активности, антропометрических данных, лабораторное и инструментальное обследование. Оценка уровня мтДНК проведена методом количественной полимеразной цепной реакции. Использовали фрагмент мтДНК с праймерами FmtMinArc 5'-CTAAATAGCCCACACGTTCCC-3' и RmtMinArc 5'-AGAGCTCCCGTGAGTGGTTA-3'. Результаты. На основании проведенного исследования оценки взаимосвязи количественного показателя мтДНК в крови пациентов с АГ, выявлено, что независимо от стадии заболевания, достоверных различий в показателях уровня мтДНК не выявлено, однако отметим, что количество копий имело тенденцию к увеличению по сравнению с условно здоровыми пациентами. При анализе сердечно-сосудистого риска обнаружено, что количественный показатель мтДНК не зависит от стадии АГ. В то же время уровень мтДНК статистически значимо повышается у пациентов с АГ очень высокого сердечно-сосудистого риска по сравнению с условно здоровыми субъектами: Me (Q1; Q3) - 56731 (42531; 129375) копий/мл против 35156 (18325; 54956) копий/мл соответственно (p = 0,015). Заключение. Уровень мтДНК у пациентов с АГ может явиться маркёром сердечно-сосудистого риска. Учитывая ранее показанную патогенетическую роль уровня мтДНК при остром коронарном синдроме, следует продолжить анализ, чувствительность которого может быть повышена за счет включения количественных показателей содержания ядерной ДНК. Studying cell-free circulating mitochondrial DNA (mtDNA) in blood plasma induces growing interest. It is assumed that an indicator of mtDNA may appear a promising clinical biomarker for assessment of the risks in the course of diseases. The aim of this study was evaluating the relationship between the quantitative indicator of mtDNA in the blood of patients with arterial hypertension (AH) and the stage of the disease and the cardiovascular risk. Methods The study included 70 patients who were divided into a group with AH (n = 51) and a control group of apparently healthy patients (n = 19). All patients signed the informed consent for examination and the processing of personal data as a part of the study. Demographic data, duration of hypertension, risk factors, heredity, physical activity, anthropometric data, results of slaboratory and instrumental examinations were recorded. Concentration of mtDNA was measured by the quantitative polymerase chain reaction. A mtDNA fragment with primers FmtMinArc 5'-CTAAATAGCCCACACGTTCCC-3' and RmtMinArc 5'-AGAGCTCCCGTGAGTGGTTA-3' was used. Results. Studying the relationships between the quantitative indicator of mtDNA in the blood and AH showed that there were no significant differences in the indicators for the level of mtDNA regardless of the AH stage. However, we noted that the number of copies tended to increase in comparison with that in conventionally healthy patients. Analysis of the cardiovascular risk showed that the quantitative indicator of mtDNA did not depend on the stage of hypertension. At the same time, the level of mtDNA was significantly increased in very high cardiovascular risk patients with AH as compared to conventionally healthy subjects: Me (LQ; UQ), 56731.2 (42531.25; 129375.0) copies/ml vs. 35156.00 (18325.00; 54956.00) copies/ml, respectively (p = 0.015). Conclusion. The level of mtDNA in AH patients is a potential a marker for cardiovascular risk as shown by the increase in mtDNA in very high cardiovascular risk patients. Taking into account the previously demonstrated pathogenetic role of the level of mtDNA in acute coronary syndrome, the analysis should be continued. The analysis sensitivity can be increased by inclusion of quantitative indicators for the content of nuclear DNA.

2012 ◽  
Vol 8 (1) ◽  
pp. 10 ◽  
Author(s):  
Roland Asmar ◽  

The worldwide morbidity and mortality burden of cardiovascular disease (CVD) is overwhelming and caused by increasing life expectancy and an epidemic of risk factors, including hypertension. Therapeutic options targeting different areas of the renin–angiotensin–aldosterone system (RAAS) to disrupt pathophysiological processes along the cardiovascular continuum are available. Angiotensin-converting enzyme (ACE) inhibitors are first-line treatments for CVD and angiotensin receptor blockers (ARBs) are suitable alternatives. Both ACE inhibitors and ARBs prevent CVD by lowering blood pressure (BP). Additionally, several studies have demonstrated that RAAS blockade can reduce cardiovascular risk beyond what might be expected from BP lowering alone. However, the ARBs are not all equally effective. Telmisartan is a long-lasting ARB that effectively controls BP over the full 24-hour period. Recently, the Ongoing telmisartan alone and in combination with ramipril global endpoint trial (ONTARGET) study showed that telmisartan reduces cardiovascular events in high cardiovascular risk patients similarly to the gold standard ACE inhibitor ramipril beyond BP lowering alone, but with a better tolerability. Based on the results of the ONTARGET and Telmisartan randomized assessment study in ACE intolerant subjects with cardiovascular disease (TRANSCEND) studies, telmisartan is indicated for the reduction of cardiovascular morbidity. This article aims to review current guidelines for the management of CVD and consider key data from clinical trials and clinical practice evaluating the role of telmisartan in CVD.


2021 ◽  
Vol 23 (1) ◽  
pp. 70-73
Author(s):  
Daria Yu. Sedykh ◽  
◽  
Natalia V. Fedorova ◽  
Vasily V. Kashtalap ◽  
◽  
...  

The article demonstrates the possibility of prescribing an effective and safe lipid-lowering combination of the most tolerated doses of statins in combination with ezetimibe, using the example of a patient with severe lipid metabolism disorders in the post-infarction period. It has been shown that in real clinical practice, patients with acute coronary syndrome and persisting high LDL values are quite common, despite of the prescription of statins. These patients need closer follow-up and wider use of combined lipid-lowering therapy by adding ezetimibe to maximally tolerated doses of statins. Current clinical guidelines allow this to be done when patients fail to achieve target LDL values (>1.4 mmol/L) with statins monotherapy. This approach is effective and safe, which is illustrated by this hereditary clinical case. In routine clinical practice mandatory lipids control is required 4–6 weeks after patient’s discharge from the hospital for acute coronary syndrome. If the target lipids values were not achieved with the maximum dosage of statins, a mandatory using the combination therapy with ezetimibe is required. Keywords: myocardial infarction, dyslipidemia, improved prognosis, statins, ezetimibe For citation: Sedykh DYu, Fedorova NV, Kashtalap VV. Possibilities of combination lipid-lowering therapy in a patient with very high cardiovascular risk (сlinical case). Consilium Medicum. 2021; 23 (1): 70–73. DOI: 10.26442/20751753.2021.1.200604


2019 ◽  
Vol 287 ◽  
pp. e199
Author(s):  
A. Cesaro ◽  
F. Gragnano ◽  
F. Fimiani ◽  
E. Moscarella ◽  
I. Pariggiano ◽  
...  

2021 ◽  
Vol 40 (9) ◽  
pp. 641-648
Author(s):  
Paulo Maia Araújo ◽  
Alzira Nunes ◽  
Sofia Torres ◽  
Carlos Xavier Resende ◽  
Sérgio Machado Leite ◽  
...  

2021 ◽  
Vol 26 (7) ◽  
pp. 4608
Author(s):  
E. I. Pavlyuk ◽  
M. V. Ionov ◽  
A. S. Alieva ◽  
N. G. Avdonina ◽  
A. N. Yakovlev ◽  
...  

Coronary artery disease (CAD) is the most common cardiovascular disease and the leading cause of morbidity and mortality. Acute coronary syndrome (ACS) as an abrupt destabilization of CAD, multiplies the risk of cardiovascular events. To reduce the incidence of recurrent cardiovascular events, timely tackling potentially reversible risk factors such as hypertension and/or hyperglycemia is imperative. However, a solid basis for a secondary prevention lies in the treatment of dyslipidemia and begins in the first hours of hospital admission. Despite considerable evidence regarding the efficacy and safety of lipid-lowering therapy, averagely only one third of patients maintain control of lipids. The main challenges are low adherence, poor continuity of medical care, and the lack of an ambulatory routine follow-up. Telehealth solutions are believed to address these barriers and may be considered as an add-on to in-person patient care. Telemonitoring of vital and laboratory parameters, remote patient counseling can be introduced into routine care delivery. Telemedicine shows promise for fostering better clinical effect, and provides health-related quality of life improvement.It is planned to conduct a pilot observational study aimed to create and to test an integrated solution, i.e. telemonitoring and remote counseling in patients of very high cardiovascular risk with ACS followed by myocardial revascularization. The goal is to determine the clinical effectiveness, i.e achievement of target values of blood pressure, lipid profile and glycemia, and patient-centeredness of this approach.


Global Heart ◽  
2015 ◽  
Vol 10 (2) ◽  
pp. e24
Author(s):  
Wael Al Mahmeed ◽  
Afzal Hussein Yusufali ◽  
Sherif Bakir ◽  
Anselm Gitt ◽  
Martin Horack ◽  
...  

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
K Dyrbus ◽  
M Gasior ◽  
M Skrzypek ◽  
T Osadnik ◽  
P Desperak ◽  
...  

Abstract Background The latest guidelines from the American Association of Clinical Endocrinologists (AACE) and the American College of Endocrinology (ACE) introduced a new “ultra-high risk” category of patients, for whom a low-density lipoprotein cholesterol (LDL-C) level <55 mg/dL (1.4 mmol/L) is advised. Purpose Based on the above, we aimed to identify the proportion of patients, who are at ultra-high/extremely-high cardiovascular (CV) risk. Method Finally, we analyzed the data of 19,781 consecutive patients included in theHyperlipidaemia Therapy in the tERtiary Cardiological cEnTer (TERCET) Registry admitted to the Polish tertiary cardiovascular centre between 2006 and 2018. Among them, there were 7,319 patients admitted with ACS: 3,085 due to ST-segment elevation myocardial infarction (STEMI), 2,256 due to non-ST-segment elevation myocardial infarction (NSTEMI), and 1,978 due to unstable angina (UA), as well as 12,462 due to stable angina (SA). According to the European Society of Cardiology (ESC), all patients included in the Registry are at very high CV risk. All of the patients included in the registry underwent coronary angiography during the hospital stay. On the basis of the multivariate analysis, we aimed at determining the subgroup of the patients with the most unfavourable 12-month outcomes and therefore to indicate the risk factors responsible for extremely-high CV risk. Results According to the results of the multivariate analysis performed with stepwise backward regression, we identified the following risk factors: LVEF<40% (odds ratio [OR]=3.51, 95% CI: 2.87–4.29), prior stroke (OR=2.28, 95% CI: 1.65–3.01), diabetic nephropathy (OR=2.16, 95% CI: 1.68–2.77), age>75 years (OR=1.84, 95% CI: 1.33–2.55), atrial fibrillation (OR=1.81, 95% CI: 1.45–2.25), acute MI at admission (OR=1.56, 95% CI: 1.26–1.95), multivessel CAD (OR=1.40, 95% CI: 1.15–1.72), prior MI (OR=1.31, 95% CI: 1.07–1.60) and lower body-mass index (OR=1.02 per 1 kg/m2+ less, 95% CI: 1.00–1.04) that might help to define the group of very high risk patients, who should be considered as of extremely-high cardiovascular risk (all p<0.05). The aggregate summary of risk factors associated with “ultra-high” risk is presented in the attached Figure. Multivariate analysis results Conclusions To our best knowledge, the presented study is the first such an analysis conducted on such a large population of very-high cardiovascular risk patients gathered in the registry of secondary cardiovascular prevention. In very-high cardiovascular risk patients, potential risk factors were identified that might help to establish the group of individuals at extremely high CV risk what contributes to higher 12-month mortality. Acknowledgement/Funding None


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