Conflicting results suggest a link between serum uric acid (SUA), inflammation and glucose/insulin homeostasis; however, the role of adiposity in this relationship is not clear. Therefore, we ...evaluated the role of different adiposity factors, including central body mass index (BMI), peripheral waist circumference (WC), and visceral adiposity visceral adipose tissue (apVAT), on the association between SUA, inflammation and glucose/insulin homeostasis among US adults.
Data were extracted from the 2005–2010 US National Health and Nutrition Examination Surveys. Overall, 16,502 participants were included in the analysis (mean age = 47.1 years, 48.2% men). Analysis of co-variance and “conceptus causal mediation” models were applied, while accounting for survey design.
Corrected models showed that subjects with higher SUA levels have a less favorable profile of inflammation and glucose/insulin homeostasis parameters (all p < 0.001). We found that all our potential mediators (BMI, WC and apVAT) had an impact (to various extents) on the link between variables, including serum C-reactive protein (CRP), apolipoprotein-B (apoB), insulin resistance markers, 2-h blood glucose (2hG) and triglyceride, and fasting blood glucose (FBG) (TyG) index (all p < .001), while none of the potential mediators (BMI, apVAT, WC) had an impact on the link between FBG and glycated hemoglobin with SUA (all p > 0.05). We have found that all of our mediators partially mediated the link between inflammation and glucose/insulin homeostasis parameters and SUA. Of note, apVAT fully mediated the association between SUA and 2hG.
By applying advanced statistical techniques, we shed light on the complex link of SUA with inflammation and glucose/insulin homeostasis and quantify the role of adiposity factors in that link.
•To evaluated the role of different adiposity factors on the association between serum uric acid, inflammation and glucose/insulin homeostasis.•We accomplished this aim by applying in large and representative sample size of the US adults.•We shed light on the complex link of SUA with inflammation and glucose/insulin homeostasis.
Metabolic syndrome (MetS) is a cluster of central obesity, dyslipidaemia, insulin resistance and hypertension. MetS frequently co-exists with non-alcoholic fatty liver disease (NAFLD), which is ...characterized by fat accumulation in the liver in the absence of alcohol abuse, viral hepatitis and other causes of chronic liver diseases. Both MetS and NAFLD are associated with an increased risk for cardiovascular disease and type 2 diabetes mellitus. There are also other associations between MetS and NAFLD. In the present narrative review, we discuss the links between MetS and NAFLD in terms of prevalence, risk factors and treatment (both lifestyle interventions and drug therapy). Such associations highlight the common pathophysiological pathways of these metabolic disorders, although data for an independent association are not robust. Nevertheless, NAFLD may be regarded as a hepatic manifestation of MetS.
The intake of dairy products has been thought to be associated with an increased risk of coronary heart diseases (CHD) and total mortality due to its relatively high content of saturated fat. ...However, reports on this association particularly among US adults are conflicting and controversial. Therefore, we used data from the 1999–2010 National Health and Nutrition Examination Surveys (NHANES) study to examine whether consumption of total dairy and dairy subgroups was associated with total and cause specific (CHD, cerebrovascular and cancer) mortality. Further we carried out a systematic review and meta-analysis of prospective studies to check for consistency with the NHANES findings.
In the NHANES cohort vital status through December 31, 2011 was ascertained. Cox proportional hazard regression models were used to relate baseline dairy intake with all-cause and cause-specific mortality. For the systematic review PubMed, SCOPUS, Web of Science and Google Scholar databases were searched (up to December 2017). The DerSimonian-Laird method and generic inverse variance methods were used for quantitative data synthesis.
In the NHANES data set of 24,474 participants, 3520 deaths occurred during follow-up. In multivariate adjusted Cox models, total mortality risk was lower when comparing the top (Q4) with the lower (Q1) quartiles of total dairy (hazard ratio HR 0.98, 95% confidence interval CI: 0.95–0.99) and cheese (HR: 0.92, 95% CI: 0.87–0.97) consumption. Using a similar model, we have found a negative association between total dairy and milk consumption with risk of cerebrovascular mortality (HR: 0.96, 95% CI: 0.94–0.98, HR: 0.93, 95% CI: 0.91–0.96, respectively), while milk consumption was associated with increased CHD mortality (HR: 1.04, 95% CI: 1.02–1.06). The meta-analysis with 636,726 participants indicated a significant inverse association between fermented dairy products and total mortality (RR: 0.97, 95% CI: 0.96–0.99), while milk consumption was associated with higher CHD mortality (RR: 1.04, 95% CI: 1.01–1.05). These findings were robust in sensitivity analyses.
Among American adults, higher total dairy consumption was associated with lower total and cerebrovascular mortality, while higher milk consumption was associated with higher risk of CHD. These findings do not support dogmatic public health advice to reduce total dairy fat consumption, although the association between milk consumption and CHD mortality requires further study.
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Cilostazol for intermittent claudication Bedenis, Rachel; Stewart, Marlene; Cleanthis, Marcus ...
Cochrane database of systematic reviews,
10/2014, Letnik:
2014, Številka:
10
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, characterised ...by pain in the legs or buttocks that occurs with exercise and which subsides with rest. Compared with age‐matched controls, people with intermittent claudication have a three‐ to six‐fold increase in cardiovascular mortality. Symptoms of intermittent claudication, walking distance, and quality of life can be improved by risk factor modification, smoking cessation, and a structured exercise programme. Antiplatelet treatment is beneficial in patients with intermittent claudication for the reduction of vascular events but has not previously been shown to influence claudication distance. This is an update of a review first published in 2007.
Objectives
To determine the effect of cilostazol (an antiplatelet treatment) on improving initial and absolute claudication distances, and in reducing mortality and vascular events in patients with stable intermittent claudication.
Search methods
For this update, the Cochrane Peripheral Vascular Diseases Group Trials Search Co‐ordinator searched the Specialised Register (last searched October 2013) and CENTRAL (2013, Issue 9).
Selection criteria
Double‐blind, randomised controlled trials (RCTs) of cilostazol versus placebo, or versus other antiplatelet agents 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 performed the meta‐analysis as a fixed‐effect model with weighted mean differences (WMDs) and 95% confidence intervals (CIs) for continuous data, and odds ratios (ORs) with 95% CIs for dichotomous data.
Main results
We included fifteen double‐blind, RCTs comparing cilostazol with placebo, or medications currently known to increase walking distance e.g. pentoxifylline. There were a total of 3718 randomised participants with treatment durations ranging from six to 26 weeks. All participants had intermittent claudication secondary to PAD. Comparisons included cilostazol twice daily, with dosages of 50 mg, 100 mg and 150 mg compared with placebo, and cilostazol 100 mg, twice daily, compared with pentoxifylline 400 mg, three times daily. The methodological quality of the trials was generally low, with the majority being at an unclear risk for selection bias, performance bias, detection bias and other bias. Attrition bias was generally low, but reporting bias was high or unclear in the majority of the studies. For eight studies data were compatible for comparison by meta‐analysis, but data for seven studies were too heterogenous to be pooled. For the studies included in the meta‐analysis, for initial claudication distance (ICD ‐ the distance walked on a treadmill before the onset of calf pain) there was an improvement in the cilostazol group for the 100 mg and 50 mg twice daily, compared with placebo (WMD 31.41 metres, 95% CI 22.38 to 40.45 metres; P < 0.00001) and WMD 19.89 metres, 95% CI 9.44 to 30.34 metres; P = 0.0002), respectively. ICD was improved in the cilostazol group for the comparison of cilostazol 150 mg versus placebo and cilostazol 100 mg versus pentoxifylline, but only single studies were used for these analyses. Absolute claudication distance (ACD ‐ the maximum distance walked on a treadmill) was significantly increased in participants taking cilostazol 100 mg and 50 mg twice daily, compared with placebo (WMD 43.12 metres, 95% CI 18.28 to 67.96 metres; P = 0.0007) and WMD 32.00 metres, 95% CI 14.17 to 49.83 metres; P = 0.0004), respectively. As with ICD, ACD was increased in participants taking cilostazol 150 mg versus placebo, but with only one study an association cannot be clearly determined. Two studies comparing cilostazol to pentoxifylline had opposing findings, resulting in an imprecise CI (WMD 13.42 metres (95% CI ‐43.51 to 70.35 metres; P = 0.64). Ankle brachial index (ABI) was lowered in the cilostazol 100 mg group compared with placebo (WMD 0.06, 95% CI 0.04 to 0.08; P < 0.00001). The single study evaluating ABI for the comparison of cilostazol versus pentoxifylline found no change in ABI.
There was no association between treatment type and all‐cause mortality for any of the treatment comparisons, but there were very few events, and therefore larger, adequately powered studies will be needed to assess if there is a relationship. Only one study evaluated individual cardiovascular events, and from this study there is no clear evidence of a difference between any of the treatment groups and risk of myocardial infarction or stroke. We evaluated adverse side effects, and in general cilostazol was associated with a higher odds of headache, diarrhoea, abnormal stool, dizziness and palpitations. We only reported quality of life measures descriptively as there was insufficient statistical detail within the studies to combine the results, although there was a possible indication in improvement of quality of life in the cilostazol treatment groups.
Authors' conclusions
Cilostazol has been shown to be of benefit in improving walking distance in people with intermittent claudication secondary to PAD. Although there is an increase in adverse side effects, they are generally mild and treatable. There is currently insufficient data on whether taking cilostazol results in a reduction of all‐cause mortality and cardiovascular events or an improvement in quality of life. Future research into the effect of cilostazol on intermittent claudication should carefully consider comparability, sample size and homogeneity when designing a study.
To investigate the association of triglycerides/glucose index (TyG index), anthropometrically predicted visceral adipose tissue (apVAT), lipid accumulation product (LAP), visceral adiposity index ...(VAI) and triglycerides (TG):high density lipoprotein-cholesterol (HDL-C) ratio with insulin resistance (IR) in adult Americans.
This study was based on data from three NHANES cycles (2005 to 2010). The TyG index was calculated as ln TG×fasting glucose/2. VAI was calculated using gender-specific formulas: men waist circumference (WC)/39.68+(1.88×body mass index (BMI)×(TG/1.03)×(1.31/HDL-C); women: WC/36.58+(1.89×BMI)×(TG/0.81)×(1.52/HDL-C). LAP index was calculated as WC–65×TG in men, and WC–58×TG in women. Correlation and regression analyses accounted for the complex sampling of database.
A total of 18,318 subjects was included in this analysis mean age 47.6Years; 48.7% (n=8918) men. The homeostatic model assessment of insulin resistance (HOMA-IR) had a significant positive correlation with the TyG index (r=0.502), LAP (r=0.551), apVAT (r=0.454), TG:HDL-C ratio (r=0.441) and VAI (r=451) (p<0.001 for all comparisons). Bland-Altman plots showed no systematic errors. The optimal cut-off to predict HOMA-diagnosed IR was 0.473 (sensitivity=74.5% and specificity=72.7%) for LAP, 0.478 (75.9%, 71.9%) for TyG, 0.391 (70.4%, 67.1%) for VAI, 0.392 (77.1% and 62.0%) for TG:HDL-C ratio and 0.381 (63.8%, 74.8%) for apVAT.
The LAP index is a simple, cheap and accurate although not perfect, surrogate marker of HOMA-diagnosed IR among adult Americans. Moreover, it has higher predictability than other screening tools which traditionally applied. Among the markers, apVAT had the highest specificity and the TG:HDL-C ratio had the highest sensitivity.
Context: The metabolic syndrome (MetS) is a cluster of metabolic abnormalities that increase the risk for type 2 diabetes mellitus and vascular disease. The common characteristics of MetS and ...hypercortisolemic conditions such as Cushing’s syndrome (CS) suggest that the pathogenesis of MetS and central obesity might involve prolonged and excessive exposure to glucocorticoids. The present review summarizes the evidence on the potential role of cortisol in the pathogenesis of MetS and discusses new therapeutic approaches for these patients.
Evidence Acquisition: Using PubMed, we searched for publications during the last 20 yr regarding the possible pathogenetic role of cortisol in the development of MetS.
Evidence Synthesis: Emerging data suggest that patients with MetS show hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis, which leads to a state of “functional hypercortisolism.” The cause for this activation of the HPA axis remains uncertain but may be partly associated with chronic stress and/or low birth weight, which are both associated with increased circulating cortisol levels and greater responsiveness of the HPA axis. Increased exposure to cortisol contributes to increased fat accumulation in visceral depots. However, cortisol metabolism is not only centrally regulated. The action of 11β-hydroxysteroid dehydrogenase-1 at the tissue level also modulates cortisol metabolism. Increased 11β-hydroxysteroid dehydrogenase-1 activity in adipose tissue and liver might contribute to the development of several features of the MetS.
Conclusions: MetS shares many characteristics of CS, and cortisol might play a role in the development of MetS at both a central and a peripheral level.
The metabolic syndrome shares many characteristics of Cushing’s syndrome, and cortisol might play a role in the development of metabolic syndrome.
Statin intolerance (SI) represents a significant public health problem for which precise estimates of prevalence are needed. Statin intolerance remains an important clinical challenge, and it is ...associated with an increased risk of cardiovascular events. This meta-analysis estimates the overall prevalence of SI, the prevalence according to different diagnostic criteria and in different disease settings, and identifies possible risk factors/conditions that might increase the risk of SI.
We searched several databases up to 31 May 2021, for studies that reported the prevalence of SI. The primary endpoint was overall prevalence and prevalence according to a range of diagnostic criteria National Lipid Association (NLA), International Lipid Expert Panel (ILEP), and European Atherosclerosis Society (EAS) and in different disease settings. The secondary endpoint was to identify possible risk factors for SI. A random-effects model was applied to estimate the overall pooled prevalence. A total of 176 studies 112 randomized controlled trials (RCTs); 64 cohort studies with 4 143 517 patients were ultimately included in the analysis. The overall prevalence of SI was 9.1% (95% confidence interval 8.0-10%). The prevalence was similar when defined using NLA, ILEP, and EAS criteria 7.0% (6.0-8.0%), 6.7% (5.0-8.0%), 5.9% (4.0-7.0%), respectively. The prevalence of SI in RCTs was significantly lower compared with cohort studies 4.9% (4.0-6.0%) vs. 17% (14-19%). The prevalence of SI in studies including both primary and secondary prevention patients was much higher than when primary or secondary prevention patients were analysed separately 18% (14-21%), 8.2% (6.0-10%), 9.1% (6.0-11%), respectively. Statin lipid solubility did not affect the prevalence of SI 4.0% (2.0-5.0%) vs. 5.0% (4.0-6.0%). Age odds ratio (OR) 1.33, P = 0.04, female gender (OR 1.47, P = 0.007), Asian and Black race (P < 0.05 for both), obesity (OR 1.30, P = 0.02), diabetes mellitus (OR 1.26, P = 0.02), hypothyroidism (OR 1.37, P = 0.01), chronic liver, and renal failure (P < 0.05 for both) were significantly associated with SI in the meta-regression model. Antiarrhythmic agents, calcium channel blockers, alcohol use, and increased statin dose were also associated with a higher risk of SI.
Based on the present analysis of >4 million patients, the prevalence of SI is low when diagnosed according to international definitions. These results support the concept that the prevalence of complete SI might often be overestimated and highlight the need for the careful assessment of patients with potential symptoms related to SI.
Non-alcoholic fatty liver disease (NAFLD) is considered to be an independent cardiovascular disease (CVD) risk factor. However, simple steatosis has a benign clinical course without excess mortality. ...In contrast, the advanced form of NAFLD, non-alcoholic steatohepatitis (NASH) with liver fibrosis increases mortality by approximately 70%, due to an increase in CVD mortality by approximately 300%. Chronic kidney disease (CKD) may be caused by NAFLD/NASH and it substantially increases CVD risk, especially in the presence of type 2 diabetes mellitus. Moreover, CKD may trigger NAFLD/NASH deterioration in a vicious cycle. NAFLD/NASH is also related to increased arterial stiffness (AS), an independent CVD risk factor that further raises CVD risk. Diagnosis of advanced liver fibrosis (mainly by simple non-invasive tests), CKD, and increased AS should be made early in the course of NAFLD and treated appropriately. Lifestyle measures and statin treatment may help resolve NAFLD/NASH and beneficially affect the CVD risk factors mentioned above.
Background and Aims
Ezetimibe reduces plasma low-density lipoprotein cholesterol (LDL-C) levels by up to 20%. However, its effect on plasma lipoprotein(a) Lp(a) concentrations in patients with ...primary hypercholesterolemia has not been defined.
Objective
Therefore, we performed a systematic review and meta-analysis to assess this effect based on the available randomized controlled trials (RCTs).
Methods
We searched the PubMed and SCOPUS databases from inception until 28 February 2017 to identify RCTs that investigated the effect of ezetimibe monotherapy on plasma Lp(a) concentrations in patients with primary hypercholesterolemia. We pooled mean percentage changes in plasma Lp(a) concentrations as a mean difference (MD) with a 95% confidence interval (CI).
Results
Seven RCTs with 2337 patients met the selection criteria and were included in the analysis. Overall pooled analysis suggested that ezetimibe 10 mg significantly reduced plasma Lp(a) concentrations in patients with primary hypercholesterolemia by − 7.06% (95% CI − 11.95 to − 2.18;
p
= 0.005) compared with placebo. No significant heterogeneity was observed (
χ
2
= 5.34;
p
= 0.5). Excluding one study from the analysis resulted in insignificant differences between the two groups (
p
= 0.2). Meta-regression did not find a significant association between the mean percentage changes in Lp(a) and other potential moderator variables, which included the mean percentage changes of LDL-C concentrations (
p
= 0.06) and baseline Lp(a) mean values (
p
= 0.46).
Conclusions
Ezetimibe monotherapy (10 mg/day) showed a small (7.06%) but statistically significant reduction in the plasma levels of Lp(a) in patients with primary hypercholesterolemia. According to current literature, this magnitude of reduction seems to have no clinical relevance. However, further studies are warranted to clarify the mechanism mediating this effect of ezetimibe and to investigate its efficacy in combination with other drugs that have shown promise in lowering Lp(a) levels.
The health outcomes associated with extremely low or high plasma concentrations of high-density lipoprotein cholesterol (HDL-C) are not well documented mainly because of the small numbers of ...participants with such values included in the clinical trials.
We prospectively investigated the association between extremely low and high HDL-C with: 1) the risk of overall, coronary heart disease (CHD), cerebrovascular and cancer mortality, and, 2) their link with inflammatory factors.
Analysis was based on subjects ≥18 years old from the National Health and Nutrition Examination Surveys (NHANES). We categorized HDL-C levels as follows: low HDL-C group ≤30 (extremely low), 30–40 (low), and ≥40 (reference) high HDL-C group = 40–80 (reference), 80–100 (high) and ≥100 mg/dl (extremely high). Cox proportional hazard regression models and analysis of covariance accounted for survey design, masked variance and sample weights.
After adjustment for age, race and sex, we found that the very low HDL-C category (<30 mg/dl) had a greater risk of total mortality (risk ratio RR: 3.00, 95%CI: 2.20–4.09). RR for CHD and stroke mortality was 2.00 and 2.53, respectively; there was no link between cancer and level of HDL-C (p = 0.235). The association between total mortality, CHD and stroke with the level of HDL-C attenuated but remained significant even after adjustment for demographics, dietary, cardiovascular risk factors and treatment for dyslipidemia (all p < 0.001). After adjustments, subjects with extremely high HDL-C levels had a higher risk of mortalities (all p < 0.001). Mexican-American ethnicity, subjects in the low level of HDL-C (30–40 mg/dl) category had higher risk of mortalities than those with a very low level (all p < 0.001). Concentration of C-reactive protein, fibrinogen and white blood count significantly decreased as the level of the HDL-C increased; these findings were robust after adjustment for demographics, dietary, cardiovascular risk factors and treatment for dyslipidemia (all p < 0.001); further subjects with extremely high HDL-C levels have a greater levels of inflammatory factors (all p < 0.001).
Both extremely low and high HDL-C levels were associated with greater risk of mortalities (total, CHD and stroke) and higher level of inflammatory factors, while there was no link between level of HDL-C and risk of cancer. Moreover, we found evidence of an HDL-C paradox in Mexican-American ethnicity participants.
•After adjustment we found that the very low HDL-C category (<30 30 mg/dl) had three times greater risk of total mortality.•RR for CHD and stroke mortality was 2.00 and 2.53, respectively; there was no link between cancer and level of HDL-C.•After adjustments, subjects with extremely high HDL-C levels had a higher risk of mortalities (all p < 0.001).•Concentration of CRP, fibrinogen and white blood count significantly decreased as the level of the HDL-C increased.
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