Statin intolerance is the inability to tolerate a dose of statin required to sufficiently reduce cardiovascular risk. With the five-step approach, more than 90% of these patients might be treated ...with statins. The principal approaches are to try not to discontinue statin therapy and to treat these patients as effectively as possible. New therapies with the proprotein convertase subtilisin-kexin type 9 inhibitors and bempedoic acid might be an effective response to these needs. In case of lack of achieved goal of the therapy nutraceuticals with confirmed low-density lipoprotein cholesterol reduction properties may be considered as a part of the lipid-lowering combination therapy.
Contrast-induced nephropathy (CIN) represents an important adverse effect of contrast media (CM) administration. Contrast-induced nephropathy is associated with prolonged hospitalization as well as ...increased cardiovascular morbidity, renal morbidity, and all-cause mortality. Several risk factors may predict CIN incidence, and various scores and ratios have been proposed to identify high-risk patients. Novel biomarkers may provide an earlier diagnosis of CIN. A multifactorial approach is required for CIN prevention including hydration, administration of low- or iso-osmolar CM, minimizing CM volume, and statin administration. Renal function may deteriorate after CM administration, even in the absence of CIN. Therefore, this deterioration may not be an “all or none” phenomenon; it may well occur in many patients receiving CM, with/without CIN, and may prove to be an underestimated risk factor. Patients should be followed up for longer periods as outpatients after CM exposure to assess kidney function and predict subsequent increased morbidity and mortality.
We aimed to evaluate the link between inflammatory score consisting of C-reactive protein (CRP) and white blood cells, serum uric acid (SUA) and atherogenic index of plasma (AIP) and the ...cardiovascular health (CVH) score.
We used the cross-sectional National Health and Nutrition Examination Survey database. Statistical analyses accounted for the survey design and sample weights.
Overall, there were 23,004 participants (mean age = 47.2 years, 46.5% males). Participants with an ideal CVH level had the highest ratio of poverty to income (3.62%, p < 0.001), as well as lower levels of CRP, SUA and AIP (p < 0.001 for all comparisons). In adjusted linear regression, a significant negative association was observed between inflammatory score (β = −0.052, p < 0.001), SUA (β = −0.041, p < 0.001) and AIP (β = −0.039, p < 0.001) and CVH score, i.e. participants with a better (greater) CVH score had a lower inflammatory score. Results from adjusted logistic regression showed reduction in the likelihood of “high-risk atherosclerosis” (defined as AIP ≥0.21) intermediate: odds ratio (OR) = 0.90, 95% confidence interval (CI):0.85–0.95, ideal: OR = 0.81, 95%CI: 0.74–0.88 and “high CVD risk” (defined as CRP ≥3 mg/l) intermediate: OR = 0.86, 95%CI:0.73–0.98, ideal: OR = 0.82, 95%CI:0.69–0.95 across the categories of CVH.
Our findings highlight that CVH metrics were associated with inflammatory score, SUA and AIP. Furthermore, participants with a better CVH score had a lower CVD risk. These results reinforce the importance of implementing healthy behaviours as proposed by the American Heart Association. If confirmed in clinical trials, this knowledge may have implications for CVD prevention and management.
•The link between inflammatory score, serum uric acid (SUA) and atherogenic index of plasma (AIP) with cardiovascular health (CVH) score was evaluated.•A negative association between SUA and CVH score was observed.•AIP was inversely related to CVH score.•Significant reductions in the odds of “high-risk atherosclerosis” and “CVD risk” were found across CVH categories.
The endothelium consists of a monolayer of Endothelial Cells (ECs) which form the inner cellular lining of veins, arteries, capillaries and lymphatic vessels. ECs interact with the blood and lymph. ...The endothelium fulfils functions such as vasodilatation, regulation of adhesion, infiltration of leukocytes, inhibition of platelet adhesion, vessel remodeling and lipoprotein metabolism. ECs synthesize and release compounds such as Nitric Oxide (NO), metabolites of arachidonic acid, Reactive Oxygen Species (ROS) and enzymes that degrade the extracellular matrix. Endothelial dysfunction represents a phenotype prone to atherogenesis and may be used as a marker of atherosclerotic risk. Such dysfunction includes impaired synthesis and availability of NO and an imbalance in the relative contribution of endothelialderived relaxing factors and contracting factors such as endothelin-1 and angiotensin. This dysfunction appears before the earliest anatomic evidence of atherosclerosis and could be an important initial step in further development of atherosclerosis. Endothelial dysfunction was historically treated with vitamin C supplementation and L-arginine supplementation. Short term improvement of the expression of adhesion molecule and endothelial function during antioxidant therapy has been observed. Statins are used in the treatment of hyperlipidaemia, a risk factor for cardiovascular disease. Future studies should focus on identifying the mechanisms involved in the beneficial effects of statins on the endothelium. This may help develop drugs specifically aimed at endothelial dysfunction.
Cilostazol for intermittent claudication Brown, Tamara; Brown, Tamara; Forster, Rachel B ...
Cochrane database of systematic reviews,
06/2021, Letnik:
2021, Številka:
6
Journal Article
Recenzirano
Odprti dostop
Background
Peripheral arterial disease (PAD) affects between 4% and 12% of people aged 55 to 70 years, and 20% of people over 70 years. A common complaint is intermittent ...claudication (exercise‐induced lower limb pain relieved by rest). These patients have a three‐ to six‐fold increase in cardiovascular mortality. Cilostazol is a drug licensed for the use of improving claudication distance and, if shown to reduce cardiovascular risk, could offer additional clinical benefits. This is an update of the review first published in 2007.
Objectives
To determine the effect of cilostazol on initial and absolute claudication distances, mortality and vascular events in patients with stable intermittent claudication.
Search methods
The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL, and AMED databases, and the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registries, on 9 November 2020.
Selection criteria
We considered double‐blind, randomised controlled trials (RCTs) of cilostazol versus placebo, or versus other drugs used to improve claudication distance in patients with stable intermittent claudication.
Data collection and analysis
Two authors independently assessed trials for selection and independently extracted data. Disagreements were resolved by discussion. We assessed the risk of bias with the Cochrane risk of bias tool. Certainty of the evidence was evaluated using GRADE. For dichotomous outcomes, we used odds ratios (ORs) with corresponding 95% confidence intervals (CIs) and for continuous outcomes we used mean differences (MDs) and 95% CIs. We pooled data using a fixed‐effect model, or a random‐effects model when heterogeneity was identified. Primary outcomes were initial claudication distance (ICD) and quality of life (QoL). Secondary outcomes were absolute claudication distance (ACD), revascularisation, amputation, adverse events and cardiovascular events.
Main results
We included 16 double‐blind, RCTs (3972 participants) comparing cilostazol with placebo, of which five studies also compared cilostazol with pentoxifylline. Treatment duration ranged from six to 26 weeks. All participants had intermittent claudication secondary to PAD. Cilostazol dose ranged from 100 mg to 300 mg; pentoxifylline dose ranged from 800 mg to 1200 mg. The certainty of the evidence was downgraded by one level for all studies because publication bias was strongly suspected. Other reasons for downgrading were imprecision, inconsistency and selective reporting.
Cilostazol versus placebo
Participants taking cilostazol had a higher ICD compared with those taking placebo (MD 26.49 metres; 95% CI 18.93 to 34.05; 1722 participants; six studies; low‐certainty evidence). We reported QoL measures descriptively due to insufficient statistical detail within the studies to combine the results; there was a possible indication in improvement of QoL in the cilostazol treatment groups (low‐certainty evidence). Participants taking cilostazol had a higher ACD compared with those taking placebo (39.57 metres; 95% CI 21.80 to 57.33; 2360 participants; eight studies; very‐low certainty evidence). The most commonly reported adverse events were headache, diarrhoea, abnormal stools, dizziness, pain and palpitations. Participants taking cilostazol had an increased odds of experiencing headache compared to participants taking placebo (OR 2.83; 95% CI 2.26 to 3.55; 2584 participants; eight studies; moderate‐certainty evidence).Very few studies reported on other outcomes so conclusions on revascularisation, amputation, or cardiovascular events could not be made.
Cilostazol versus pentoxifylline
There was no difference detected between cilostazol and pentoxifylline for improving walking distance, both in terms of ICD (MD 20.0 metres, 95% CI ‐2.57 to 42.57; 417 participants; one study; low‐certainty evidence); and ACD (MD 13.4 metres, 95% CI ‐43.50 to 70.36; 866 participants; two studies; very low‐certainty evidence). One study reported on QoL; the study authors reported no difference in QoL between the treatment groups (very low‐certainty evidence). No study reported on revascularisation, amputation or cardiovascular events. Cilostazol participants had an increased odds of experiencing headache compared with participants taking pentoxifylline at 24 weeks (OR 2.20, 95% CI 1.16 to 4.17; 982 participants; two studies; low‐certainty evidence).
Authors' conclusions
Cilostazol has been shown to improve walking distance in people with intermittent claudication. However, participants taking cilostazol had higher odds of experiencing headache. There is insufficient evidence about the effectiveness of cilostazol for serious events such as amputation, revascularisation, and cardiovascular events. Despite the importance of QoL to patients, meta‐analysis could not be undertaken because of differences in measures used and reporting. Very limited data indicated no difference between cilostazol and pentoxifylline for improving walking distance and data were too limited for any conclusions on other outcomes.
Background
Quercetin, the most abundant dietary flavonol, has antioxidant effects in cardiovascular disease, but the evidence regarding its effects on blood pressure (BP) has not been conclusive. We ...assessed the impact of quercetin on BP through a systematic review and meta‐analysis of available randomized controlled trials.
Methods and Results
We searched PUBMED, Cochrane Library, Scopus, and EMBASE up to January 31, 2015 to identify placebo‐controlled randomized controlled trials investigating the effect of quercetin on BP. Meta‐analysis was performed using either a fixed‐effects or random‐effect model according to I2 statistic. Effect size was expressed as weighted mean difference (WMD) and 95% CI. Overall, the impact of quercetin on BP was reported in 7 trials comprising 9 treatment arms (587 patients). The results of the meta‐analysis showed significant reductions both in systolic BP (WMD: −3.04 mm Hg, 95% CI: −5.75, −0.33, P=0.028) and diastolic BP (WMD: −2.63 mm Hg, 95% CI: −3.26, −2.01, P<0.001) following supplementation with quercetin. When the studies were categorized according to the quercetin dose, there was a significant systolic BP and diastolic BP‐reducing effect in randomized controlled trials with doses ≥500 mg/day (WMD: −4.45 mm Hg, 95% CI: −7.70, −1.21, P=0.007 and −2.98 mm Hg, 95% CI: −3.64, −2.31, P<0.001, respectively), and lack of a significant effect for doses <500 mg/day (WMD: −1.59 mm Hg, 95% CI: −4.44, 1.25, P=0.273 and −0.24 mm Hg, 95% CI: −2.00, 1.52, P=0.788, respectively), but indirect comparison tests failed to significant differences between doses.
Conclusions
The results of the meta‐analysis showed a statistically significant effect of quercetin supplementation in the reduction of BP, possibly limited to, or greater with dosages of >500 mg/day. Further studies are necessary to investigate the clinical relevance of these results and the possibility of quercetin application as an add‐on to antihypertensive therapy.
Introduction
Uric acid (UA), the final product of purine catabolism, may be associated with an increased risk of cardiovascular disease.
Aim
The aim of this meta-analysis of randomized ...placebo-controlled trials was to evaluate whether lowering serum UA (SUA) levels with allopurinol is associated with improved flow-mediated dilation (FMD), a validated marker of early vascular damage.
Methods
A literature search was carried out from inception until 20 June 2017. Meta-analysis was performed using an inverse variance-weighted, random-effects model with standardized mean difference (SMD) as the effect size estimate.
Results
Meta-analysis of data from the ten eligible randomized controlled trials (RCTs), with 670 subjects, suggested a significant increase in FMD following allopurinol treatment (weighted mean difference WMD 1.79%, 95% confidence interval CI 1.01–2.56,
p
< 0.001;
I
2
: 86.77%). The effect size was robust and remained significant after omission of each single study. Subgroup analyses of RCTs based on the administered dose or duration of treatment did not reveal any significant impact of these variables on FMD change. Nor was a significant association found between allopurinol-induced changes in SUA levels and FMD (slope 0.46,
p
= 0.253), whereas baseline FMD significantly influenced the degree of FMD improvement following allopurinol treatment (slope 0.52,
p
= 0.022). Nitroglycerin-mediated dilation was not altered by allopurinol treatment (WMD 0.88%, 95% CI − 1.15–2.91,
p
= 0.395;
I
2
: 80.88%).
Conclusion
This meta-analysis of available RCTs suggests a significant benefit from allopurinol intake in increasing FMD in humans, independent of its effect on SUA levels.
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