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Toxins Sep 2022Vascular calcification contributes to cardiovascular morbidity and mortality. A recently developed serum calcification propensity assay is based on the... (Review)
Review
Vascular calcification contributes to cardiovascular morbidity and mortality. A recently developed serum calcification propensity assay is based on the half-transformation time (T50) from primary calciprotein particles (CPPs) to secondary CPPs, reflecting the serum's endogenous capacity to prevent calcium phosphate precipitation. We sought to identify and review the results of all published studies since the development of the T50-test by Pasch et al. in 2012 (whether performed in vitro, in animals or in the clinic) of serum calcification propensity. To this end, we searched PubMed, Elsevier EMBASE, the Cochrane Library and Google Scholar databases from 2012 onwards. At the end of the selection process, 57 studies were analyzed with regard to the study design, sample size, characteristics of the study population, the intervention and the main results concerning T50. In patients with primary aldosteronism, T50 is associated with the extent of vascular calcification in the abdominal aorta. In chronic kidney disease (CKD), T50 is associated with the severity and progression of coronary artery calcification. T50 is also associated with cardiovascular events and all-cause mortality in CKD patients, patients on dialysis and kidney transplant recipients and with cardiovascular mortality in patients on dialysis, kidney transplant recipients, patients with ischemic heart failure and reduced ejection fraction, and in the general population. Switching from acetate-acidified dialysate to citrate-acidified dialysate led to a longer T50, as did a higher dialysate magnesium concentration. Oral administration of magnesium (in CKD patients), phosphate binders, etelcalcetide and spironolactone (in hemodialysis patients) was associated with a lower serum calcification propensity. Serum calcification propensity is an overall marker of calcification associated with hard outcomes but is currently used in research projects only. This assay might be a valuable tool for screening serum calcification propensity in at-risk populations (such as CKD patients and hemodialyzed patients) and, in particular, for monitoring changes over time in T50.
Topics: Biomarkers; Calcium Phosphates; Citrates; Dialysis Solutions; Humans; Magnesium; Renal Insufficiency, Chronic; Spironolactone; Vascular Calcification
PubMed: 36136575
DOI: 10.3390/toxins14090637 -
Hellenic Journal of Cardiology : HJC =... 2022The real-world implementation of heart failure (HF) guidelines remains unclear. Our present systematic review and meta-analysis aimed to examine the rate of HF patients... (Meta-Analysis)
Meta-Analysis Review
The real-world implementation of heart failure (HF) guidelines remains unclear. Our present systematic review and meta-analysis aimed to examine the rate of HF patients receiving guideline-directed treatment to identify the proportion of under-treatment patients and those who are treated with optimal doses, to evaluate the correlation of under-treatment patients' characteristics with the prescribed therapy, and finally, to evaluate the combined effect of the above on incidental mortality and rehospitalization. We conducted a systematic review of the literature indexed in Medline. We screened 1224 papers and excluded 1166 as they did not meet the inclusion criteria. Of the remaining 58 papers, which were evaluated by studying the full text, 11 papers that referred to 45866 patients were finally studied in this work. Angiotensin-Converting-Enzyme Inhibitor (ACEI) and Angiotensin II-Receptor Blocker (ARB) use was estimated to be 80.9% (95% CI: 73.9%, 86.4%), β-blockers' use was 78% (95% CI: 70.4%, 84.1%), Mineralocorticoid Receptor Antagonists' use was 47.4% (95% Cl 41.6%, 53.4%), and cardiac resynchronization therapy's use was 5.8% (95% Cl 3.4%, 9.6%). Meta-regression analysis showed that prescription of more than the half of target dose of ACEI/ARBs was found to be associated with reduced all-cause mortality (Z = -3.61, P = 0.0003), while the relationship with β-blockers was borderline (Z = -1.56, P = 0.11). A satisfactory adherence to the prescription of guideline-recommended treatment in patients with HF was observed. However, the under titration of the life-saving HF drugs need to be improved as only ultimate adherence to guideline-directed treatments may lead to the reduction of HF burden.
Topics: Adrenergic beta-Antagonists; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Heart Failure; Humans; Mineralocorticoid Receptor Antagonists; Stroke Volume
PubMed: 35508296
DOI: 10.1016/j.hjc.2022.04.006 -
Vascular Pharmacology Jun 2023The use of hydrochlorothiazide has recently been linked to skin cancer in observational studies. This may be explained by its photosensitizing properties, but... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The use of hydrochlorothiazide has recently been linked to skin cancer in observational studies. This may be explained by its photosensitizing properties, but photosensitivity has also been reported for other antihypertensive drugs. We conducted a systematic review and meta-analysis to compare skin cancer risk among antihypertensive drug classes and individual blood pressure lowering drugs.
METHODS
We searched Medline, Embase, Cochrane and the Web of Science and included studies that investigated the association between antihypertensive medication exposure and non-melanoma skin cancer (NMSC) or cutaneous malignant melanoma (CMM). We combined the extracted odds ratios (OR) using a random effects model.
RESULTS
We included 42 studies with a total of 16,670,045 subjects. Diuretics, in particular hydrochlorothiazide, were examined most frequently. Only 2 studies provided information about antihypertensive co-medication. Exposure to diuretics (OR 1.27 [1.09-1.47]) and calcium channel blockers (OR 1.06 [1.04-1.09]) was associated with an increased risk for NMSC. The increased risk for NMSC was only observed in case control studies and studies that did not correct for sun exposure, skin phototype or smoking. Studies that did correct for covariates as well as cohort studies did not show a significantly increased risk for NMSC. Egger's test revealed a significant publication bias for the subgroup of diuretics, hydrochlorothiazide and case-control studies concerning NMSC (p < 0.001).
CONCLUSION
The available studies investigating the potential skin cancer risk that is associated with antihypertensive medication have significant shortcomings. Also, a significant publication bias is present. We found no increased skin cancer risk when analyzing cohort studies or studies that corrected for important covariates. (PROSPERO (CRD42020138908)).
Topics: Humans; Antihypertensive Agents; Skin Neoplasms; Hydrochlorothiazide; Melanoma; Diuretics; Hypertension
PubMed: 37084802
DOI: 10.1016/j.vph.2023.107173 -
PLoS Neglected Tropical Diseases Apr 2023Scorpion envenomation is associated with several complications. One of the most serious complications is the cardiac involvement in the form of myocarditis that remains...
BACKGROUND
Scorpion envenomation is associated with several complications. One of the most serious complications is the cardiac involvement in the form of myocarditis that remains the main reason for mortalities associated with scorpion envenomation. The present review aims to elucidate clinical and paraclinical findings associated with scorpion-related myocarditis, and to explore different management strategies and subsequent outcomes.
METHODS
We searched PubMed, Web of Science, Scopus, and Google Scholar for articles related to keywords of myocarditis associated with scorpion envenomation up to May 1, 2022. Each article was carefully reviewed by two independent researchers. In case of disagreement for inclusion, we sought a third researcher opinion.
RESULTS
A total of 703 cases from 30 case reports and 34 case series were included in our review. Myocarditis associated with scorpion envenomation was usually reported in children presenting with cardiopulmonary symptoms including pulmonary edema (60.7%) and shock or hypotension (45.8%). The most common ECG findings are sinus tachycardia (82%) followed by ST-T changes (64.6%). The management typically included inotropes (especially dobutamine), prazosin, diuretics, nitroglycerine and digoxin, when indicated. Mechanical ventilation was required in 36.7% of the patients. Mortality in confirmed scorpion-related myocarditis cases is estimated at 7.3%. Almost all survived cases showed rapid recovery and improvement in the left ventricular function.
CONCLUSION
Even though myocarditis associated with scorpion envenomation is rare, it remains a serious and in some of cases a fatal consequence of scorpion sting. In case of relative presentations, particularly in envenomed children, diagnosis of myocarditis should be considered. Early screening using serial cardiac markers and echocardiography can guide the treatment. Prompt treatment that focuses on cardiogenic shock and pulmonary edema usually results in a favorable outcome.
Topics: Child; Humans; Animals; Scorpion Stings; Myocarditis; Pulmonary Edema; Dobutamine; Respiration, Artificial; Scorpions
PubMed: 37018229
DOI: 10.1371/journal.pntd.0011219 -
Journal of Clinical Hypertension... Mar 2013Many hypertensive patients require ≥2 drugs to achieve blood pressure targets. This study aims to review and analyze the clinical studies conducted with dual or triple... (Meta-Analysis)
Meta-Analysis Review
Many hypertensive patients require ≥2 drugs to achieve blood pressure targets. This study aims to review and analyze the clinical studies conducted with dual or triple combination of angiotensin II receptor blockers (ARBs), calcium channel blockers (CCBs), and diuretics. Medical literature between January 1990 and April 2012 was reviewed systematically and data from eligible studies were abstracted. Data were analyzed using random-effects models. Of the 224 studies screened, 7563 eligible patients from 11 studies were included. Triple combinations of ARBs (olmesartan or valsartan), CCBs (amlodipine), and diuretics (hydrochlorothiazide) at any dose provided more blood pressure reduction in office and 24-hour ambulatory measurements than any dual combination of these molecules (P<.0001 for both). Significantly more patients achieved blood pressure targets with triple combinations (odds ratio, 2.16; P<.0001). Triple combinations did not increase adverse event risk (odds ratio, 0.96; P=.426). Triple combinations at any dose seem to decrease blood pressure more effectively than dual combination of the same molecules without any remarkable risk elevation for adverse events. Further prospective studies evaluating the efficacy and safety of triple combinations, especially in the form of single pills, are required.
Topics: Angiotensin Receptor Antagonists; Antihypertensive Agents; Blood Pressure; Calcium Channel Blockers; Diuretics; Drug Therapy, Combination; Humans; Hypertension; Treatment Outcome
PubMed: 23458592
DOI: 10.1111/jch.12040 -
The Cochrane Database of Systematic... Jun 2018Chronic (present > 48 hours) non-hypovolaemic hyponatraemia occurs frequently, can be caused by various conditions, and is associated with shorter survival and longer... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Chronic (present > 48 hours) non-hypovolaemic hyponatraemia occurs frequently, can be caused by various conditions, and is associated with shorter survival and longer hospital stays. Many treatments, such as fluid restriction or vasopressin receptor antagonists can be used to improve the hyponatraemia, but whether that translates into improved patient-important outcomes is less certain.
OBJECTIVES
This review aimed to 1) look at the benefits and harms of interventions for chronic non-hypovolaemic hypotonic hyponatraemia when compared with placebo, no treatment or head-to-head; and 2) determine if benefits and harms vary in absolute or relative terms dependent on the specific compound within a drug class, on the dosage used, or the underlying disorder causing the hyponatraemia.
SEARCH METHODS
We searched the Cochrane Kidney and Transplant Register of Studies up to 1 December 2017 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. We also screened the reference lists of potentially relevant studies, contacted authors, and screened the websites of regulatory agencies.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) and quasi-RCTs that compared the effects of any intervention with placebo, no treatment, standard care, or any other intervention in patients with chronic non-hypovolaemic hypotonic hyponatraemia. We also included subgroups with hyponatraemia from studies with broader inclusion criteria (e.g. people with chronic heart failure or people with cirrhosis with or without hyponatraemia), provided we could obtain outcomes for participants with hyponatraemia from the report or the study authors.
DATA COLLECTION AND ANALYSIS
Two authors independently extracted data and assessed risk of bias. We expressed treatment effects as mean difference (MD) for continuous outcomes (health-related quality of life, length of hospital stay, change from baseline in serum sodium concentration, cognitive function), and risk ratio (RR) for dichotomous outcomes (death, response and rapid increase in serum sodium concentration, hypernatraemia, polyuria, hypotension, acute kidney injury, liver function abnormalities) together with 95% confidence intervals (CI).
MAIN RESULTS
We identified 35 studies, enrolling 3429 participants. Twenty-eight studies (3189 participants) compared a vasopressin receptor antagonist versus placebo, usual care, no treatment, or fluid restriction. In adults with chronic, non-hypovolaemic hypotonic hyponatraemia, vasopressin receptor antagonists have uncertain effects on death at six months (15 studies, 2330 participants: RR 1.11, 95% CI 0.92 to 1.33) due to risk of selective reporting and serious imprecision; and on health-related quality of life because results are at serious risk of performance, selective reporting and attrition bias, and suffer from indirectness related to the validity of the Short Form Health Survey (SF-12) in the setting of hyponatraemia. Vasopressin receptor antagonists may reduce hospital stay (low certainty evidence due to risk of performance bias and imprecision) (3 studies, 610 participants: MD -1.63 days, 95% CI -2.96 to -0.30), and may make little or no difference to cognitive function (low certainty evidence due to indirectness and imprecision). Vasopressin receptor antagonists probably increase the intermediate outcome of serum sodium concentration (21 studies, 2641 participants: MD 4.17 mmol/L, 95% CI 3.18 to 5.16), corresponding to two and a half as many people having a 5 to 6 mmol/L increase in sodium concentration compared with placebo at 4 to 180 days (moderate certainty evidence due to risk of attrition bias) (18 studies, 2014 participants: RR 2.49, 95% CI 1.95 to 3.18). But they probably also increase the risk of rapid serum sodium correction - most commonly defined as > 12 mmol/L/d (moderate certainty evidence due to indirectness) (14 studies, 2058 participants: RR 1.67, 95% CI 1.16 to 2.40) and commonly cause side-effects such as thirst (13 studies, 1666 participants: OR 2.77, 95% CI 1.80 to 4.27) and polyuria (6 studies, 1272 participants): RR 4.69, 95% CI 1.59 to 13.85) (high certainty evidence). The potential for liver toxicity remains uncertain due to large imprecision. Effects were generally consistent across the different agents, suggesting class effect.Data for other interventions such as fluid restriction, urea, mannitol, loop diuretics, corticosteroids, demeclocycline, lithium and phenytoin were largely absent.
AUTHORS' CONCLUSIONS
In people with chronic hyponatraemia, vasopressin receptor antagonists modestly raise serum sodium concentration at the cost of a 3% increased risk of it being rapid. To date there is very low certainty evidence for patient-important outcomes; the effects on mortality and health-related quality of life are unclear and do not rule out appreciable benefit or harm; there does not appear to be an important effect on cognitive function, but hospital stay may be slightly shorter, although available data are limited. Treatment decisions must weigh the value of an increase in serum sodium concentration against its short-term risks and unknown effects on patient-important outcomes. Evidence for other treatments is largely absent.Further studies assessing standard treatments such as fluid restriction or urea against placebo and one-another would inform practice and are warranted. Given the limited available evidence for patient-important outcomes, any study should include these outcomes in a standardised manner.
Topics: Antidiuretic Hormone Receptor Antagonists; Chronic Disease; Humans; Hyponatremia; Length of Stay; Quality of Life; Randomized Controlled Trials as Topic; Sodium
PubMed: 29953167
DOI: 10.1002/14651858.CD010965.pub2 -
The Cochrane Database of Systematic... Feb 2015Blood transfusions are associated with significant morbidity and mortality. Prophylactic administration of loop diuretics (furosemide, bumetanide, ethacrynic acid, or... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Blood transfusions are associated with significant morbidity and mortality. Prophylactic administration of loop diuretics (furosemide, bumetanide, ethacrynic acid, or torsemide) is common practice, especially among people who are at risk for circulatory overload, pulmonary oedema or both.
OBJECTIVES
This review aimed to determine if the prophylactic administration of loop diuretics (furosemide, bumetanide, ethacrynic acid, or torsemide) provides a therapeutic advantage (that is, a favourable risk benefit ratio) in adults and children who are recipients of any blood product transfusion versus placebo, no treatment, or general fluid restriction measures.
SEARCH METHODS
We searched the Cochrane Renal Group's Specialised Register to 13 January 2015 through contact with the Trials' Search Co-ordinator using search terms relevant to this review.
SELECTION CRITERIA
All randomised controlled trials (RCTs) and quasi-RCTs assessing a loop diuretic in patients receiving any blood transfusion were considered for inclusion.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed study quality and extracted data. Study authors were contacted for additional information. Results were to be expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes, and mean difference (MD) and 95% CI for continuous outcomes. Mean effect sizes were to be calculated using the random-effects models.
MAIN RESULTS
We included four studies that involved 100 participants. Furosemide was the only diuretic investigated in all four studies.None of the included studies assessed the clinically important outcomes noted in our protocol. The studies focused on various markers of respiratory function. An improvement in fraction of inspired oxygen (in favour of furosemide) was noted in one study. An improvement in pulmonary capillary wedge pressure (in favour of furosemide) was noted in two studies.
AUTHORS' CONCLUSIONS
There was insufficient evidence to determine whether premedicating people undergoing blood transfusion with loop diuretics prevents clinically important transfusion-related morbidity. Due to the continued use of prophylactic loop diuretics during transfusions, and because this review highlights the absence of evidence to justify this practice, well-conducted RCTs are needed. Given the high mortality, severe morbidity and increasing incidence of transfusion-associated circulatory overload, determining the therapeutic utility of pre-transfusion loop diuresis is an urgent need.
Topics: Adult; Body Water; Confidence Intervals; Furosemide; Humans; Infant, Newborn; Infant, Premature; Pulmonary Edema; Randomized Controlled Trials as Topic; Sodium Potassium Chloride Symporter Inhibitors; Transfusion Reaction
PubMed: 25685898
DOI: 10.1002/14651858.CD010138.pub2 -
Journal of Clinical Hypertension... Apr 2017The purpose of this study was to assess the effects of renin-angiotensin system (RAS) inhibitors vs other antihypertensive agents on cardiovascular outcomes in... (Comparative Study)
Comparative Study Meta-Analysis Review
The purpose of this study was to assess the effects of renin-angiotensin system (RAS) inhibitors vs other antihypertensive agents on cardiovascular outcomes in hypertensive black patients. The authors performed a systematic review and meta-analysis of studies that compared the effects of angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) with calcium channel blockers (CCBs), diuretics, and β-blockers in hypertensive black patients on cardiovascular outcomes. A total of 38,983 patients with a mean age of 60 years and mean follow-up of 4 years were included in our meta-analysis. No significant differences were found in all-cause mortality, myocardial infarction, heart failure, and cardiovascular mortality rates among patients treated with RAS inhibitors compared with CCBs, diuretics, and β-blockers. The incidence of stroke was significantly increased in patients treated with RAS inhibitors compared with CCBs (odds ratio, 1.56; 95% confidence interval, 1.31-1.87 [P<.00001]; I =0%) and diuretics (odds ratio, 1.59; 95% confidence interval, 1.16-2.17 [P=.004]; I =56%) but not β-blockers.
Topics: Adrenergic beta-Antagonists; Aged; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Black People; Calcium Channel Blockers; Diuretics; Female; Heart Failure; Humans; Hypertension; Incidence; Male; Middle Aged; Myocardial Infarction; Observational Studies as Topic; Randomized Controlled Trials as Topic; Renin-Angiotensin System; Stroke
PubMed: 27378313
DOI: 10.1111/jch.12867 -
British Journal of Clinical Pharmacology May 2021Plasma renin activity (PRA) is regarded as a marker of sodium and fluid homeostasis in patients with primary hypertension. Whether effects of diuretics on PRA differ... (Meta-Analysis)
Meta-Analysis Review
AIMS
Plasma renin activity (PRA) is regarded as a marker of sodium and fluid homeostasis in patients with primary hypertension. Whether effects of diuretics on PRA differ according to class of diuretic, whether diuretics lead to a sustained increase in PRA, and whether changes in PRA relate to those in blood pressure (BP) is unknown. We performed a systematic review and meta-analysis of trials investigating the antihypertensive effects of diuretic therapy in which PRA and/or other biomarkers of fluid homeostasis were measured before and after treatment.
METHODS
Three databases were searched: MEDLINE, EMBASE and The Cochrane Central Register of Controlled Trials. Titles were firstly screened by title and abstract for relevancy before full-text articles were assessed for eligibility according to a predefined inclusion/exclusion criteria.
RESULTS
A total of 1684 articles were retrieved of which 61 met the prespecified inclusion/exclusion criteria. PRA was measured in 30/61 studies. Diuretics led to a sustained increase in PRA which was similar for different classes of diuretic (standardised mean difference [95% confidence interval] 0.481 [0.362, 0.601], 0.729 [0.181, 1.28], 0.541 [0.253, 0.830] and 0.548 [0.159, 0.937] for thiazide, loop, mineralocorticoid receptor antagonists/potassium-sparing and combination diuretics respectively, Q = 0.897, P = .826), and did not relate to the average decrease in blood pressure.
CONCLUSION
In antihypertensive drug trials, diuretics lead to a sustained increase in average PRA, which is similar across different classes of diuretic and unrelated to the average reduction in blood pressure.
Topics: Antihypertensive Agents; Blood Pressure; Diuretics; Humans; Hypertension; Renin
PubMed: 33085785
DOI: 10.1111/bcp.14597 -
Annals of Pediatric Cardiology 2022The concept of cardiorenal syndrome (CRS) is derived from the crosstalk between the heart and kidneys in pathological conditions. Despite the rising importance of CRS,... (Review)
Review
The concept of cardiorenal syndrome (CRS) is derived from the crosstalk between the heart and kidneys in pathological conditions. Despite the rising importance of CRS, there is a paucity of information on the understanding of its pathophysiology and management, increasing both morbidity and mortality for patients. This review summarizes the existing conceptual pathophysiology of different types of CRS and delves into the associated therapeutic modalities with a focus on pediatric cases. Prospective or retrospective observational studies, comparative studies, case reports, case-control, and cross-sectional studies that include pediatric patients with CRS were included in this review. Literature was searched using PubMed, EMBASE, and Google Scholar with keywords including "cardio-renal syndrome, type," "reno-cardio syndrome," "children," "acute kidney injury," and "acute decompensated heart failure" from January 2000 to January 2021. A total of 14 pediatric studies were ultimately included and analyzed, comprising a combined population of 3608 children of which 32% had CRS. Of the 14 studies, 57% were based on type 1 CRS, 14% on types 2 and 3 CRS, and 7% were on types 4 and 5 CRS. The majority of included studies were prospective cohort, although a wide spectrum was observed in terms of patient age, comorbidities, etiologies, and treatment strategies. Commonly observed comorbidities in CRS type 1 were hematologic, oncologic, cardiology-related side effects, muscular dystrophy, and pneumonia/bronchiolitis. CRS, particularly type 1, is prevalent in children and has a significant risk of mortality. The current treatment regimen primarily involves diuretics, extracorporeal fluid removal, and treatment of underlying etiologies and comorbidities.
PubMed: 37152514
DOI: 10.4103/apc.apc_50_22