scholarly journals Trimethylamine oxide and its possible role in the development and progression of cardiovascular disease

2021 ◽  
Vol 20 (6) ◽  
pp. 3014
Author(s):  
A. I. Kochetkov ◽  
M. V. Klepikova ◽  
O. D. Ostroumova
Keyword(s):  
Cardiovascular Events ◽  
Large Scale ◽  
Randomized Clinical Trials ◽  
Arterial Disease ◽  
Brain Regions ◽  
Prognostic Effect ◽  
Trimethylamine Oxide ◽  
Increased Risk ◽  
Peripheral Arterial ◽  
Hepatoprotective Agents

Cardiovascular diseases continue to be the leading cause of death throughout the world and in Russia. Therefore, new possible risk factors for their development and progression are being studied. To date, information have been accumulated on unfavorable prognostic effect of elevated trimethylamine oxide (TMAO) levels on cardiovascular events, and the possible role of phospholipids (PLs) is being discussed. The aim of this review was to analyze the literature data on the potential relationship of TMAO and PLs with cardiovascular risk (CVR), as well as possible solutions to this problem. The search and analysis of publications was performed using Elibrary, PubMed, Medline, and Google Scholar databases in the period from their creation to 2021. It was found that high TMAO concentrations can have pro-inflammatory effects, stimulate atherogenesis and increase platelet aggregation. An increase in the blood TMAO levels increases the risk of cardiovascular events in patients with coronary artery disease, is associated with an increased risk of cardiovascular and all-cause death in patients with peripheral arterial disease and heart failure, and correlates with the extent of brain regions involved in stroke. The most important part in TMAO formation is taken by the gut microbiota, which metabolizes substrates, including PLs, to trimethylamine, which, when absorbed, is converted into TMAO in the liver. The analysis of available studies shows that the excessive intake of PLs into the gastrointestinal tract and the increased TMAO production are potentially interrelated with an increase in CVR. At the same time, PLs are currently used as drugs, in particular, as hepatoprotective agents. In view of this, large-scale randomized clinical trials are needed to study the CVR profile in patients receiving such therapy. Currently, other hepatoprotective agents are available that are devoid of such potential risks, since they do not contain PLs. One of these agents is ursodeoxycholic acid, which has proven its effectiveness and safety, including in patients with high CVR in routine clinical practice.

Effects of lipid-lowering therapy on major adverse limb events in patients with peripheral arterial disease: A meta-analysis of randomized clinical trials

Vascular ◽  
2021 ◽  
pp. 170853812110439
Author(s):  
Walter Masson ◽  
Martín Lobo ◽  
Leandro Barbagelata ◽  
Graciela Molinero ◽  
Ignacio Bluro
Keyword(s):  
Clinical Trials ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Arterial Disease ◽  
Lipid Lowering ◽  
Placebo Control ◽  
Lipid Lowering Therapy ◽  
Lowering Therapy ◽  
Increased Risk ◽  
Peripheral Arterial

Objective Patients with peripheral artery disease (PAD) are at increased risk of major adverse limb events (MALE). Furthermore, MALE have several clinical implications and a poor prognosis, so prevention is a fundamental issue. The main objective of the present meta-analysis of randomized clinical trials is to evaluate the effect of different lipid-lowering therapies on MALE incidence in patients with PAD. Methods A meta-analysis of randomized studies that evaluated the use of lipid-lowering therapy in patients with PAD and reported MALE was performed, after searching the PubMed/MEDLINE, Embase, ScieLO, Google Scholar, and Cochrane Controlled Trials databases. A fixed- or random-effects model was used. Results Five randomized clinical trials including 11,603 patients were identified and considered eligible for the analyses (5903 subjects were allocated to receive lipid-lowering therapy, while 5700 subjects were allocated to the respective placebo/control arms). The present meta-analysis revealed that lipid-lowering therapy was associated with a lower incidence of MALE (OR: 0.76, 95% confidence interval: 0.66–0.87; I2: 28%) compared to placebo/control groups. The sensitivity analysis shows that the results are robust. Conclusion This study demonstrated that the use of lipid-lowering therapy compared with the placebo/control arms was associated with a marked reduction in the risk of MALE. Physicians involved in the monitoring and treatment of patients with PAD must work hard to ensure adequate lipid-lowering medication in these patients.

D-dimer as a marker for cardiovascular and arterial thrombotic events in patients with peripheral arterial disease

2013 ◽  
Vol 110 (08) ◽  
pp. 233-243 ◽  
Author(s):  
Hugo Cate ◽  
Arina ten Cate-Hoek ◽  
Marie-Claire Kleinegris
Keyword(s):  
Cardiovascular Events ◽  
Meta Analysis ◽  
Arterial Disease ◽  
Specific Information ◽  
Increased Risk ◽  
Near Term ◽  
Artery Disease ◽  
Peripheral Arterial ◽  
D Dimer

SummaryPeripheral artery disease (PAD) is associated with an increased risk for cardiovascular events. D-dimers are a marker for hypercoagulability and are linked with thrombotic events in patients with venous as well as arterial thrombosis. The predictive value of plasma D-dimer levels in relation to cardiovascular events in patients with PAD is not unambiguously established. It was our objective to gather evidence evaluating the value of D-dimer as a predictor of arterial thrombotic events patients with PAD. The Pubmed, Embase, and Cochrane databases were searched (January 1980-November 2012), and 65 abstracts were found. The strategy was supplemented with manual review of reference lists. Case-control, cohort or prospective cohort studies that measured fibrin D-dimer in patients with PAD, were included. Studies were excluded if there was no follow-up for arterial thrombotic events or when no specific information on D-dimer was available. The search yielded 10 studies for our analysis, comprising 2,420 patients with PAD, with a total of 1,036 cardiovascular events in 10,599 patient-years. Two studies with a follow-up of one year showed that fibrin D-dimer predicts both deterioration of PAD and subsequent thrombotic events. Five out of six studies with a median follow-up of 2–4 years revealed that an increased D-dimer is predictive of various arterial thrombotic events including mortality. Two studies with a longer follow-up (over 6 years) did not show an independent association between increased D-dimer levels, arterial thrombotic events and CVD mortality. In conclusion, an increased D-dimer appeared to be independently associated with a two times increased risk of near-term cardiovascular events (relative risk 2.30, 95% confidence interval 1.43–3.68). However formal meta-analysis was only feasible for four out of 10 included studies. Due to the extended heterogeneity of the included studies cautious interpretation of these data is warranted.

scholarly journals What Is Currently the Role of TcPO2 in the Choice of the Amputation Level of Lower Limbs? A Comprehensive Review

2021 ◽  
Vol 10 (7) ◽  
pp. 1413
Author(s):  
Judith Catella ◽  
Anne Long ◽  
Lucia Mazzolai
Keyword(s):  
Arterial Disease ◽  
Major Amputation ◽  
Lower Limbs ◽  
Limb Amputation ◽  
Quality Of Data ◽  
Amputation Level ◽  
Increased Risk ◽  
Transcutaneous Oximetry ◽  
Peripheral Arterial

Some patients still require major amputation for lower extremity peripheral arterial disease treatment. The purpose of pre-operative amputation level selection is to determine the most distal amputation site with the highest healing probability without re-amputation. Transcutaneous oximetry (TcPO2) can detect viable tissue with the highest probability of healing. Several factors affect the accuracy of TcPO2; nevertheless, surgeons rely on TcPO2 values to determine the optimal amputation level. Background about the development of TcPO2, methods of measurement, consequences of lower limb amputation level, and the place of TcPO2 in the choice of the amputation level are reviewed herein. Most of the retrospective studies indicated that calf TcPO2 values greater than 40 mmHg were associated with a high percentage of successful wound healing after below-knee-amputation, whereas values lower than 20 mmHg indicated an increased risk of unsuccessful healing. However, a consensus on the precise cut-off value of TcPO2 necessary to assure healing is missing. Ways of improvement for TcPO2 performance applied to the optimization of the amputation-level are reported herein. Further prospective data are needed to better approach a TcPO2 value that will promise an acceptable risk of re-amputation. Standardized TcPO2 measurement is crucial to ensure quality of data.

Complex antithrombotic therapy and bleeding risk in patients with peripheral arterial disease

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
A Tseng ◽  
S Bhatt ◽  
M Girardo ◽  
D Liedl ◽  
P Wennberg ◽  
...  
Keyword(s):  
Peripheral Arterial Disease ◽  
Triple Therapy ◽  
Major Bleeding ◽  
Antithrombotic Therapy ◽  
Oral Anticoagulants ◽  
Bleeding Risk ◽  
Arterial Disease ◽  
Risk Of Bleeding ◽  
Increased Risk ◽  
Peripheral Arterial

Abstract Introduction Antiplatelet therapy is the cornerstone of treatment for many atherosclerotic vascular pathologies including peripheral arterial disease (PAD). Patients with PAD often have comorbid conditions that require complex antithrombotic therapy, i.e. combined antiplatelet and anticoagulation. Methods All adult patients undergoing ankle brachial index (ABI) measurements were included in the study. ABI values between 1.00 and 1.40 were considered normal, and values below 1.00 or above 1.40 were considered PAD. Demographic, comorbidity and outcome data were obtained using diagnostic codes from the electronic health record. Three medication classes were analyzed: aspirin, non-aspirin oral antiplatelets (e.g. P2Y12 inhibitors) and oral anticoagulants (warfarin and the direct oral anticoagulants). Medication use was determined for patients who had been on a medication for at least one year. Cox proportional hazard analysis for the time to first bleeding event was analyzed. Bleeding was defined as any bleeding requiring medical evaluation (including clinically-relevant non-major bleeding and major bleeding). Results In all, 40,144 patients were included in the analysis (mean age 66±15, 43% female). Patients with PAD were more likely to be on double therapy (one antiplatelet with anticoagulation) (28% vs 19%) and triple therapy (dual antiplatelet with anticoagulation) (10% vs 4%). Unadjusted hazard ratios for bleeding risk showed increased risk of bleeding for patients with PAD (1.18, 95% confidence interval [CI]: 1.08–1.29), though the association is no longer present after adjustment for antithrombotic therapy. Adjusting for age, sex and PAD class, compared to no antithrombotic therapy, there was increased risk of bleeding for monotherapy (1.91, 95% CI: 1.61–2.26), double therapy (3.40, 95% CI: 2.89–4.00) and triple therapy (5.00, 95% CI: 4.21–5.96). Among medications, aspirin and anticoagulant use was independently associated with the greatest increase in risk of bleeding. Conclusion Patients in PAD are at increased risk of bleeding secondary to antithrombotic therapy. Complex antithrombotic therapy with double or triple therapy confer additional bleeding risk, particularly regimens containing aspirin and oral anticoagulants. Funding Acknowledgement Type of funding source: None

scholarly journals Extremely elevated lipoprotein (a) as an independent risk factor for peripheral arterial disease in large patient cohort

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M.R Poudel ◽  
S Kirana ◽  
D Stoyanova ◽  
K.P Mellwig ◽  
D Hinse ◽  
...  
Keyword(s):  
Peripheral Arterial Disease ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Arterial Disease ◽  
P Value ◽  
Lipoprotein A ◽  
Large Patient ◽  
Increased Risk ◽  
Revascularization Therapy ◽  
Peripheral Arterial

Abstract Background Elevated lipoprotein (a) [LP (a)] levels are an independent, genetic, and causal factor for cardiovascular disease and associated with myocardial infarction (MI). Although the association between circulating levels of lipoprotein(a) [Lp(a)] and risk of coronary artery disease (CAD) is well established, its role in risk of peripheral arterial disease (PAD) remains unclear. PAD affects over 236 million individuals and follows ischaemic heart disease (IHD) and cerebrovascular disease (CVD) as the third leading cause of atherosclerotic cardiovascular morbidity worldwide. LP (a) is genetically determined, stable throughout life and yet refractory to drug therapy. While 30 mg/dl is considered the upper normal value for LP (a) in central Europe, extremely high LP (a) levels (>150mg/dl) are rare in the general population. The aim of our study was to analyse the correlation between lipoprotein (a) [LP (a)] levels and an incidence of PAD in high-risk patients. Patients and methods We reviewed the LP (a) concentrations of 52.898 consecutive patients admitted to our cardiovascular center between January 2004 and December 2014. Of these, 579 patients had LP (a) levels above 150 mg/dl (mean 181.45±33.1mg/dl). In the control collective LP (a) was <30mg/dl (n=350). Other atherogenic risk factors in this group were HbA1c 6.58±1.65%, low density lipoprotein (LDL) 141.99±43.76 mg/dl, and body mass index 27.81±5.61. 54.40% were male, 26.07% were smokers, 93.2% had hypertension, and 24% had a family history of cardiovascular diseases. More than 82.6% were under statins. The mean glomerular filtration rate (GFR) was 69.13±24.8 ml/min [MDRD (Modification of Diet in Renal Disease)]. Results 45.00% (n=261) of the patients with LP (a) >150mg/dl had PAD. The prevalence of PAD in patients with LP (a) <30mg/dl in our control collective was 15.8%. (P- Value 0.001). Patients with LP (a) >150mg/dl had a significantly increased risk for PAD (Odds ratio 4.36, 95% CI 2.94–6.72, p: 0.001). 19.1% of patients were re-vascularized by percutaneous angioplasty (PTA) and 7.09% of patients had to undergo peripheral vascular bypass (PVB). Mean LP (a) level in patients with PAD was 182.6±31.61. Conclusion Elevated LP (a) levels above 150 mg/dl are associated with a significantly increased risk of PAD in our collective and it confirms our hypothesis. Over one fourth of these patients had severe PAD and requiring revascularization therapy. We need more prospective studies to confirm our findings. Funding Acknowledgement Type of funding source: None

scholarly journals Increased risk of peripheral arterial disease in polymyalgia rheumatica: a population-based cohort study

2009 ◽  
Vol 11 (2) ◽  
pp. R50 ◽  
Author(s):  
Kenneth J Warrington ◽  
Elena P Jarpa ◽  
Cynthia S Crowson ◽  
Leslie T Cooper ◽  
Gene G Hunder ◽  
...  
Keyword(s):  
Cohort Study ◽  
Peripheral Arterial Disease ◽  
Polymyalgia Rheumatica ◽  
Arterial Disease ◽  
Population Based ◽  
Increased Risk ◽  
Peripheral Arterial

Abstract P081: Markers of Endothelial Function and Peripheral Arterial Disease among Women

Circulation ◽  
2013 ◽  
Vol 127 (suppl_12) ◽  
Author(s):  
Sona Rivas-Tumanyan ◽  
Kenneth J Mukamal ◽  
Jennifer K Pai ◽  
Kaumudi J Joshipura
Keyword(s):  
Myocardial Infarction ◽  
Peripheral Arterial Disease ◽  
Endothelial Function ◽  
Conditional Logistic Regression ◽  
Relative Weight ◽  
Serum Levels ◽  
Arterial Disease ◽  
Blood Draw ◽  
Increased Risk ◽  
Peripheral Arterial

Introduction: Markers of endothelial function may be associated with increased risk for cardiovascular disease; however, prospective data for peripheral arterial disease (PAD) are limited. We evaluated the hypothesis that serum markers of endothelial dysfunction are associated with an increased risk of PAD among women. Methods: We conducted a nested case-control study within an ongoing prospective cohort of U.S. female nurses (Nurses’ Health Study). Among 32,826 NHS participants who provided blood samples in 1989-1990, after excluding those who had myocardial infarction, coronary heart disease, stroke, or carotid artery surgery prior to the PAD diagnosis, we included all incident PAD cases that occurred between 1990 and 2008 and were confirmed by medical records. Each case was individually matched with three eligible controls using risk-set sampling, by age, smoking, date of blood draw, and fasting status. We evaluated the association between serum levels of soluble intercellular adhesion molecule (ICAM-1), E-selectin, and the risk of PAD, using conditional logistic regression analysis. Results: Complete biomarker data from 1990 was available for 144 cases and 431 controls. After accounting for matching factors, baseline ICAM-1 levels were associated with higher risk of PAD (RR for highest (T3) vs. lowest (T1) tertile=1.75, 95% CI: 1.05-2.90). The association was attenuated and no longer significant (RR T3 vs. T1=1.37, 95% CI: 0.75-2.49) after adjusting for serum levels of HDL and LDL-cholesterol, family history of myocardial infarction, relative weight, reported aspirin and cholesterol-lowering medication use, hypertension and diabetes diagnoses, physical activity, and pack-years of smoking. Additional adjustment for CRP levels further attenuated the relative risk (RR T3 vs. T1= 1.24, 95% CI: 0.67-2.29). We did not observe any significant association between baseline E-selectin levels and the risk of PAD (multivariate- and CRP-adjusted RR T3 vs. T1=0.93, 95% CI: 0.54-1.59). Conclusions: There was no association between ICAM-1 and E-selectin and subsequent PAD in this cohort of U.S women.

scholarly journals Increased Risk of Peripheral Arterial Disease After Hip Replacement

Medicine ◽  
2015 ◽  
Vol 94 (19) ◽  
pp. e870 ◽  
Author(s):  
Tzu-Yi Chou ◽  
Ta-Wei Su ◽  
Herng-Jeng Jou ◽  
Pei-Yu Yang ◽  
Hsuan-Ju Chen ◽  
...  
Keyword(s):  
Peripheral Arterial Disease ◽  
Hip Replacement ◽  
Arterial Disease ◽  
Increased Risk ◽  
Peripheral Arterial
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