Using machine learning to aid treatment decision and risk assessment for severe three-vessel coronary artery disease.

BACKGROUND: Three-vessel disease (TVD) with a SYNergy between PCI with TAXus and cardiac surgery (SYNTAX) score of ≥ 23 is one of the most severe types of coronary artery disease. We aimed to take advantage of machine learning to help in decision-making and prognostic evaluation in such patients. METHODS: We analyzed 3786 patients who had TVD with a SYNTAX score of ≥ 23, had no history of previous revascularization, and underwent either coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) after enrollment. The patients were randomly assigned to a training group and testing group. The C4.5 decision tree algorithm was applied in the training group, and all-cause death after a median follow-up of 6.6 years was regarded as the class label. RESULTS: The decision tree algorithm selected age and left ventricular end-diastolic diameter (LVEDD) as splitting features and divided the patients into three subgroups: subgroup 1 (age of ≤ 67 years and LVEDD of ≤ 53 mm), subgroup 2 (age of ≤ 67 years and LVEDD of > 53 mm), and subgroup 3 (age of > 67 years). PCI conferred a patient survival benefit over CABG in subgroup 2. There was no significant difference in the risk of all-cause death between PCI and CABG in subgroup 1 and subgroup 3 in both the training data and testing data. Among the total study population, the multivariable analysis revealed significant differences in the risk of all-cause death among patients in three subgroups. CONCLUSIONS: The combination of age and LVEDD identified by machine learning can contribute to decision-making and risk assessment of death in patients with severe TVD. The present results suggest that PCI is a better choice for young patients with severe TVD characterized by left ventricular dilation.

Direct Bilirubin Levels Predict Long-Term Outcomes in Patients With Acute Coronary Syndrome Under Different Glucose Metabolism Status: A 6.5-Year Cohort Study of Three-Vessel Disease.

Background: There is controversy over the relationship between bilirubin and coronary artery disease. This study aimed to evaluate the predictive value of direct bilirubin (DB) in patients with complex acute coronary syndrome (ACS). Methods: From April 2004 to February 2011, 5,322 ACS patients presenting with three-vessel disease were consecutively enrolled. Disease severity and complexity were determined by SYNTAX score (SS) and SS II. The primary endpoint was all-cause death, and the secondary endpoints were major adverse cardiovascular and cerebrovascular events (MACCE). Stratification of normal glucose regulation, prediabetes, and diabetes was based on a previous diagnosis, hypoglycemic medications, fasting blood glucose, and hemoglobin A1c. Results: Subjects were divided into quartiles according to baseline DB (µmol/L): Q1 (0-1.6), Q2 (1.61-2.20), Q3 (2.21-2.80), and Q4 (>2.80). Multivariable logistic regression analysis showed that DB was an independent predictor of intermediate-high SS. During a median follow-up time of 6.5 years, elevated DB was associated with more all-cause death (p < 0.001) but not MACCE. DB remained to be predictive of all-cause death in the multivariable Cox regression model (Q2 vs. Q1: HR 1.043, 95% CI 0.829-1.312, p = 0.719; Q3 vs. Q1: HR 1.248, 95% CI 1.001-1.155, p = 0.048; Q4 vs. Q1: HR 1.312, 95% CI 1.063-1.620, p = 0.011). When subjects are stratified according to glucose metabolism regulation and treatment strategies, the predictivity of DB was only profound in patients with diabetes or with conservative treatment. Additionally, incorporating DB further improved the discrimination and reclassification abilities of SS II for risk prediction. Conclusion: DB is a potential biomarker for predicting lesion severity and long-term outcomes in ACS patients.

Evaluation of blood pressure lowering effect by generic and brand-name antihypertensive drugs treatment: a multicenter prospective study in China.

BACKGROUND: Generic drugs are bioequivalent to their brand-name counterparts; however, concerns still exist regarding the effectiveness and safety of generic drugs because of small sample sizes and short follow-up time in most studies. The purpose of this study was to evaluate the long-term antihypertensive efficacy, cost-effectiveness and cardiovascular outcomes of generic drugs compared with brand-name drugs. METHODS: In a multicenter, community-based study including 7955 hypertensive patients who were prospectively followed up for an average of 2.5 years, we used the propensity-score-matching method to match the patients using brand-name drugs to those using generic drugs in a ratio of 1:2, 2176 patients using brand-name drugs and 4352 patients using generic drugs. RESULTS: There were no significant differences between generic drugs and brand-name drugs in blood pressure (BP)-lowering efficacy, BP control rate, and cardiovascular outcomes including coronary heart disease and stroke. The adjusted mean (95% confidence interval [CI]) of systolic BP (SBP)-lowering was -7.9 mmHg (95% CI, -9.9 to -5.9) in the brand-name drug group and -7.1 mmHg (95% CI, -9.1 to -5.1) in the generic drug group after adjusting for age, sex, body mass index, number of antihypertensive drugs and traditionally cardiovascular risk factors. Among patients aged <60 years, brand-name drugs had a higher BP control rate (47% vs. 41%; P = 0.02) and a greater effect in lowering SBP compared with generic drugs, with the between-group difference of 1.5 mmHg (95% CI, 0.2-2.8; P = 0.03). BP control rate was higher in male patients using brand-name drugs compared with those using generic drugs (46% vs. 40%; P = 0.01). Generic drugs treatment yielded an average annual incremental cost-effectiveness ratio of $315.4 per patient per mmHg decrease in SBP compared with brand-name drugs treatment. CONCLUSIONS: Our data suggested that generic drugs are suitable and cost-effective in improving hypertension management and facilitating public health benefits, especially in low- and middle-income areas.

Low Serum Uric Acid Levels Promote Hypertensive Intracerebral Hemorrhage by Disrupting the Smooth Muscle Cell-Elastin Contractile Unit and Upregulating the Erk1/2-MMP Axis.

Intracerebral hemorrhage (ICH) is a catastrophic stroke with high mortality, and the mechanism underlying ICH is largely unknown. Previous studies have shown that high serum uric acid (SUA) levels are an independent risk factor for hypertension, cardiovascular disease (CVD), and ischemic stroke. However, our metabolomics data showed that SUA levels were lower in recurrent intracerebral hemorrhage (R-ICH) patients than in ICH patients, indicating that lower SUA might contribute to ICH. In this study, we confirmed the association between low SUA levels and the risk for recurrence of ICH and for cardiac-cerebral vascular mortality in hypertensive patients. To determine the mechanism by which low SUA effects ICH pathogenesis, we developed the first low SUA mouse model and conducted transcriptome profiling of the cerebrovasculature of ICH mice. When combining these assessments with pathological morphology, we found that low SUA levels led to ICH in mice with angiotensin II (Ang II)-induced hypertension and aggravated the pathological progression of ICH. In vitro, our results showed that p-Erk1/2-MMP axis were involved in the low UA-induce degradation of elastin, and that physiological concentrations of UA and p-Erk1/2-specific inhibitor exerted a protective role. This is the first report describing to the disruption of the smooth muscle cell (SMC)-elastin contractile units in ICH. Most importantly, we revealed that the upregulation of the p-Erk1/2-MMP axis, which promotes the degradation of elastin, plays a vital role in mediating low SUA levels to exacerbate cerebrovascular rupture during the ICH process.

Prognostic Values of Serum Chloride and Sodium Levels in Patients with Three-vessel Disease.

OBJECTIVE: Identification of new risk factors is needed to improve prediction of adverse outcomes in patients with three-vessel disease (TVD). The present study aimed to evaluate the prognostic values of serum chloride and sodium levels in patients with TVD. METHODS: We used data from a prospective cohort of consecutive patients with angiographically confirmed TVD. The primary endpoint was all-cause death. Cox proportional hazard regression was used to analyze the relationship of serum chloride and sodium levels with long-term outcomes of TVD patients. RESULTS: A total of 8,318 participants with available serum chloride and sodium data were included in this analysis. At baseline, patients in the low tertiles group of serum chloride level (⪕ 102.0 mmol/L) or serum sodium level (⪕ 139.0 mmol/L) had more severe disease conditions. During a median follow-up of 7.5-year, both low serum chloride level and low serum sodium level were found to be associated with an increased risk for mortality in univariate analysis. However, when both parameters were incorporated into a multivariate model, only low serum sodium level remained to be an independent predictor of all-cause death (hazard ratio: 1.16, 95% confidence interval: 1.01-1.34, P = 0.041). Modest but significant improvement of discrimination was observed after incorporating serum sodium level into the Synergy between percutaneous coronary intervention (PCI) with Taxus and Cardiac Surgery score. CONCLUSION: Serum sodium level is more strongly associated with long-term outcomes of TVD patients compared with serum chloride level. Low serum sodium level is an independent risk factor for mortality, but only provides modest prognostic information beyond an established risk model.

The era of clinical application of gene diagnosis in cardiovascular diseases is coming.

Gene diagnosis refers to the use of genetic testing in the diagnosis of inheritable conditions, which has gradually been applied in clinical practice with the completion of the gene sequencing efforts of the Human Genome Project and the advancement of gene detection technology. In the specialty field of cardiology, monogenic cardiovascular diseases are defined as monogenic inherited diseases with cardiovascular damage as the only phenotype, or accompanied by cardiovascular damage. Although the incidence of such diseases is relatively low, in the country of China with its vast population of 1.33 billion, the sheer volume of patients with monogenic cardiovascular diseases is alarming. With early onset, severe symptoms, and poor prognosis, delays in diagnosis and treatment of monogenic cardiovascular diseases often have serious consequences. Gene testing is perfectly suited for early diagnosis of monogenic cardiovascular diseases, especially for "pre-symptomatic" diagnosis. In this article, we generally review the characteristics of common monogenic cardiovascular diseases, summarize the progress of the standardized application of gene testing technology in clinical practice, describe the applicable population and condition of genetic testing for different monogenic cardiovascular diseases, analyze the practicality of genetic diagnosis of these inheritable conditions, and provide guidance on identifying suitable candidates for gene diagnosis. In conclusion, gene diagnosis provides new insights into the way physicians diagnose diseases, and is well-positioned to guide clinical decision making and treatment, especially in cardiology.

Aortic Aneurysm in Takayasu Arteritis.

BACKGROUND: Aortic aneurysm (AA) is a severe complication of Takayasu arteritis (TA). This study aimed to evaluate the prevalence, clinical and imaging features, management and long-term outcomes of AA in patients with TA. MATERIALS AND METHODS: A retrospective study was performed of TA patients with AA admitted to Fuwai Hospital from 1996-2015. Baseline clinical data and follow-up data of TA patients with AA were collected and analyzed. RESULTS: Thirty-nine (4.2%) of 934 patients with TA were identified with AA that was related to vasculitis. The mean age at disease onset was 31 ± 10 years, with a female-to-male ratio of 1.79:1. The ascending aorta was the most common site of the aneurysmal lesion (18, 33.3%), and the most frequent manifestations associated with AA were chest tightness (12, 30.8%) and shortness of breath (12, 30.8%), which were usually concomitant with aortic valve insufficiency. Involvement of multiple sites in AA was found in 8 patients (20.5%), and multiple AAs were found in 5 patients (12.8%). No significant difference was observed in clinical and imaging findings between sexes. Of 25 patients (64.1%) with a median 72-month follow-up, 1 patient suffered from heart failure owing to perivalvular leakage, and 1 patient died, possibly related to severe complications of the operation. CONCLUSIONS: The prevalence of AA is relatively low in Chinese patients with TA. AA seems to develop more frequently in male patients with TA. Management should consider location and size of AA, complexity of vessel lesions and disease status. Long-term follow-up is indispensable.

Admission white blood cell count predicts short-term clinical outcomes in patients with uncomplicated Stanford type B acute aortic dissection.

OBJECTIVES: Inflammation has been shown to be related with acute aortic dissection (AAD). The present study aimed to evaluate the association of white blood cell counts (WBCc) on admission with both in-hospital and long-term all-cause mortality in patients with uncomplicated Stanford type B AAD. METHODS: From 2008 to 2010, a total of 377 consecutive patients with uncomplicated type B AAD were enrolled and then followed up. Clinical data and WBCc on admission were collected. The primary end points were in-hospital death and long-term all-cause death. RESULTS: The in-hospital death rate was 4.2%, and the long-term all-cause mortality rate was 6.9% during a median follow-up of 18.9 months. WBCc on admission was identified as a risk factor for in-hospital death by univariate Cox regression analysis as both a continuous variable and a categorical variable using a cut off of 11.0 × 109 cell/L (all P < 0.05). After adjusting for age, sex and other risk factors, elevated admission WBCc was still a significant predictor for in-hospital death as both a continuous variable [hazard ratio (HR): 1.052, 95% CI: 1.024-1.336, P = 0.002] and a categorical variable using a cut off of 11.0 × 109 cell/L (HR: 2.056, 95% CI: 1.673-5.253, P = 0.034). No relationship was observed between WBCc on admission and long-term all-cause death. CONCLUSIONS: Our results indicate that elevated WBCc upon admission might be used as a predictor for increased risk of in-hospital death in uncomplicated type B AAD. There might be no predictive value of WBCc for the long-term survival of type B AAD.

Aortic Dissection in Takayasu Arteritis.

BACKGROUND: Aortic dissection (AD) is a rare complication of Takayasu arteritis (TA). The clinical presentation and long-term management outcomes of AD in patients with TA have not been well described. MATERIALS AND METHODS: We conducted a retrospective study of patients with TA along with AD admitted to Fuwai Hospital between January 1985 and March 2016. Clinical data and follow-up data were collected and analyzed. RESULTS: Of the 1,154 patients with TA, we identified 10 patients (0.87%) with AD, which was likely to be associated with vasculitis. All patients were females with a median age at TA onset of 26.5 years (range: 18.3-33.3 years), had type III TA and had a history of hypertension, which was much more common than that in previously reported cases. Stanford type B or DeBakey category III was the dominant anatomic classification of AD. Four patients developed AD after the diagnosis of TA, and 6 developed AD near the time of TA diagnosis. Nine patients underwent conservative treatment, whereas 1 patient underwent endovascular repair due to extensive dissection. At a median 70.5-month follow-up (range: 31.5-138.5), we found that 7 patients had no AD progression, 1 patient had progressed without symptoms, 1 patient was lost and 1 patient died. CONCLUSIONS: Patients with TA along with long-standing and poorly controlled hypertension are liable to develop AD. Those with extensive AD in TA should be carefully treated and intensively followed up.

Familial hypertrophic cardiomyopathy caused by a de novo Gly716Arg mutation of the ß-myosin heavy chain.

The present study was performed to identify the genotype of a hypertrophic cardiomyopathy family and investigate the clinicopathogenic characteristics and prognostic features of relevant genetic abnormalities. Target sequence capture sequencing was performed to screen for pathogenic alleles in a 32-year-old female patient (proband). Sanger sequencing was carried out to verify the results. Sanger sequencing was also performed on other family members to identify allele carriers. A survival analysis was carried out using published literature and our findings. We found that the proband and her son harboured a Gly716Arg sequence variant of the ß-myosin heavy chain. Neither the proband's father nor the mother were carriers of this sequence variant; thus, the mutation was classified as "de novo". Further survival analysis revealed that female patients appear to have a longer life expectancy compared with males. Our study may provide an effective approach for the genetic diagnosis of hypertrophic cardiomyopathy.

Association of the MicroRNA-146a SNP rs2910164 with Ischemic Stroke Incidence and Prognosis in a Chinese Population.

We conducted a case-control study investigating the association between the single-nucleotide polymorphism rs2910164 in microRNA (miR)-146a and the risk and prognosis of stroke. We recruited a total of 1139 ischemic stroke patients and 1585 sex- and age-matched control subjects. After a median follow-up period of 4.5 years, 1071 of these ischemic stroke patients were then recruited for a prospective study. Our study revealed that rs2910164 was not associated with ischemic stroke incidence (odds ratio = 1.00; 95% confidence interval (CI) = 0.80-1.24; p = 0.985) by multivariate logistic regression. Meta-analysis of our case-control study and three others on Asian populations also suggested that there was no relationship between rs2910164 and ischemic stroke incidence. The significance of differences in long-term outcomes was examined by the log-rank test of the respective comparison groups. The prospective study showed that rs2910164 led to a 1.56-fold increased risk of stroke recurrence (hazard ratio (HR) = 1.56; 95% CI = 1.10-2.20; p = 0.013) and a 2.13-fold increased risk of death caused by cardiovascular disease or stroke (Csdeath) (HR = 2.13; 95% CI = 1.31-3.46; p = 0.002). The independent association of rs2910164 with stroke prognosis was evaluated using Cox regression models. Therefore, rs2910164 appears to be a strong predictor of stroke prognosis but not of stroke incidence in Asian populations.

Single Nucleotide Polymorphism rs10919543 in FCGR2A/FCGR3A Region Confers Susceptibility to Takayasu Arteritis in Chinese Population.

BACKGROUND: Takayasu arteritis (TA) is a rare inflammatory arteriopathy of unknown etiology. The aim of this study was to investigate the genetic susceptibility to TA in a Chinese population. METHODS: Four single nucleotide polymorphisms (SNPs) those locate in the IL12B region (rs56167332), the MLX region (rs665268), the FCGR2A/FCGR3A locus (rs10919543), and the HLA-B/MICA locus (rs12524487), associated with TA in different population, were genotyped in 123 Chinese TA patients and 147 healthy controls from January 2013 to August 2014. A Chi-square test was used to test for genotype/allele frequencies variants. RESULTS: Among the four SNPs, rs10919543 was found to be significantly associated with TA in the studied population. The GG genotype of rs10919543 at the FCGR2A/FCGR3A locus is a high risk factor (odds ratio [OR] = 6.532, 95% confidence interval [CI] = 2.402 - 17.763, P < 0.001) for TA. Among TA patients, the level of eosinophil granulocytes (Eos) in the peripheral blood was observed to be higher in the GG group of rs10919543 (n = 23, Eos = 0.11 [0.08, 0.17] ×109/L) than the GA + AA group (n = 100, Eos = 0.08 [0.05, 0.13] ×109/L, P = 0.028). No correlation between the genotypes of the other three SNPs and TA patients was observed. CONCLUSIONS: Our findings revealed unique genetic pattern in Chinese TA patients that may be partly responsible for the higher risk of TA in this population. FCGR2A/FCGR3A-related immune disorder might contribute to the etiology of TA.

A functional variant in the coding region of CAMTA2 is associated with left ventricular hypertrophy by affecting the activation of Nkx2.5-dependent transcription.

OBJECTIVE: The calmodulin-binding transcription activator 2 (CAMTA2) promotes transcription of genes involved in cardiac hypertrophy through its interaction with Nkx2.5 and is an indispensable transcription coactivator for cardiac hypertrophy. We hypothesized that variants in the coding region of CAMTA2 would affect its function and confer a risk of cardiac hypertrophy. METHODS: The effects of the variant rs238234 on the activity of the atrial natriuretic factor promoter and on the cardiomyocytes hypertrophy were assessed in the H9C2 cell line and primary neonatal rat cardiomyocytes, respectively. Furthermore, the association of this variant with left ventricular hypertrophy (LVH) was tested in hypertensive patients with and without hypertrophy (N = 325 and 697), and this analysis was replicated in an independent population of 987 hypertensive patients without hypertrophy and 463 hypertensive patients with hypertrophy. RESULTS: We found that the G allele of rs238234 activated the atrial natriuretic factor promoter more strongly than the C allele. The cell size of cardiomyocytes was larger in the presence of the Ad-CAMTA2 G allele, and the G allele was associated with significantly increased susceptibility to LVH in hypertensive [odds ratio (OR), 1.29; P = 0.009]. In the discovery cohort, after adjusting for age and sex, the GG genotype was significantly associated with increased LVH risk (OR, 1.75; P = 0.015). There was little attenuation of the ORs (1.62; P < 0.05) when adjusting for BMI, heart rate, blood pressure, smoking, and drinking and further adjusting all covariates including lipid levels and other major risk factors. However, the GC genotype did not show any association with LVH using three regressive models. Replication in the second study yielded similar results. CONCLUSION: Our results provide evidence that the rs238234 GG genotype in the coding region of CAMTA2 may increase the risk of LVH by affecting the activation of Nkx2.5-dependent transcription.

Association between Common Genetic Variants of α2A-, α2B-, and α2C-Adrenergic Receptors and Orthostatic Hypotension.

BACKGROUND: The genetic background associated with the dysregulation of orthostatic blood pressure remains poorly understood. The sympathetic nervous system plays a pivotal role in the regulation of blood pressure, as well as in response to positional changes. The essential role of adrenergic receptors in the sympathetic nervous system prompted us to hypothesize that common genetic variants of the α2-adrenergic receptor might contribute to the dysregulation of orthostatic blood pressure in general populations. This study is to explore the association between the polymorphisms of the α2-adrenergic receptor genes and the occurrence of orthostatic hypotension in Chinese populations. METHODS: The polymorphisms ADRA2A C-1291G (rs1800544), ADRA2B 301-303 I/D (rs28365031), and ADRA2C 322-325 I/D (rs61767072) were genotyped in 317 patients with orthostatic hypotension and 664 age- and gender-matched controls. Logistic regression analyses, adjusted for multiple comparisons, were used to determine the association between the allele/genotype of each ADRA2 gene and the risk of orthostatic hypotension. RESULTS: No significant association was found between the ADRA2A C-1291G, ADRA2B 301-303 I/D, and ADRA2C 322-325 I/D polymorphisms and orthostatic hypotension. CONCLUSIONS: We concluded that the common polymorphisms in the alpha2-adrenergic receptor gene is not associated with orthostatic hypotension risk in Chinese.

Prevalence of Liddle Syndrome Among Young Hypertension Patients of Undetermined Cause in a Chinese Population.

Liddle syndrome, an autosomal dominant form of monogenic hypertension, has been regarded as a rare disorder, which leads to many Liddle syndrome patients being misdiagnosed and experiencing severe complications at an early age. Little is known about the prevalence of Liddle syndrome. In this study, the authors investigated the prevalence of Liddle syndrome confirmed by genetic testing among young hypertension patients of undetermined causes in China. A total of 330 hypertensive patients aged 14 to 40 years after exclusion of common secondary causes of hypertension were enrolled and serum potassium concentrations were measured. Patients with hypokalemia underwent genetic testing of the 13th exon of genes encoding ß and γ subunits of the epithelial sodium channel (ENaC). Diagnosis was established by identification of mutations that destroy the PY motif of ENaC. Five patients were diagnosed with Liddle syndrome (prevalence, 1.52%), as well as 12 of their relatives. These patients with Liddle syndrome presented with an earlier onset of hypertension, a stronger family history of hypertension, and higher blood pressure than those with essential hypertension. All patients had hypokalemia and suppressed plasma renin activity. The results demonstrated that Liddle syndrome is an important etiology of hypertension in this young population. Screening of Liddle syndrome should focus on young hypertension patients, particularly those with early penetrance, hypokalemia, and low renin levels after exclusion of common secondary causes.

Differential expression of microRNAs in aortic tissue and plasma in patients with acute aortic dissection.

BACKGROUND: Biomarker-assisted diagnosis of acute aortic dissection (AAD) is important for diagnosis and treatment. However, identification of biomarkers for AAD in blood is a challenging task. The aim of this study is to search for new potentially microRNA (miRNAs) biomarkers in AAD. METHODS: The miRNAs expression profiles in ascending aortic tissue and plasma were examined by microarray analysis in two sets or groups. The tissue group was composed of four patients with AAD and four controls of healthy male organ donors. The plasma group included 20 patients with AAD and 20 controls without cardiovascular disease. Bioinformatics was used to analyze the potential targets of the differentially expressed miRNAs. RESULTS: Our study revealed that in AAD patients, the aortic tissue had 30 differentially expressed miRNAs with 13 up-regulated and 17 down-regulated, and plasma had 93 differentially expressed miRNAs, of which 33 were up-regulated and 60 were down-regulated. Four miRNAs were found to be up-regulated in both aortic tissue and plasma in AAD patients. The predicted miRNA targets indicated the four dysregulated miRNAs mainly targeted genes that were associated with cell-cell adhesion, extracellular matrix metabolism, cytoskeleton organization, inflammation, and multiple signaling pathways related to cellular cycles. CONCLUSIONS: Four miRNAs, which are up-regulated both in aortic tissue and in plasma in AAD patients, have been identified in this study. These miRNAs might be potential diagnostic biomarkers for AAD. Larger sample investigations are needed for further verification.

Meta-analysis of nonsteroidal anti-inflammatory drug use and risk of atrial fibrillation.

Atrial fibrillation (AF) is the most common arrhythmia in clinical practice. The goal of the present study was to quantify the association between use of nonsteroidal anti-inflammatory drugs (NSAIDs) and risk of AF incidence. MEDLINE and EMBASE were searched for studies that reported risk of AF associated with nonaspirin NSAID use. Combined relative risk (RR) estimates and 95% confidence intervals (CIs) were calculated using the random-effects model. Stratified meta-analyses were used to discern which patients were at the highest risk of AF due to NSAID use. Five studies were identified that met the inclusion criteria, 3 of which additionally reported specifically on the association between selective NSAIDs and risk of AF. Overall, NSAID use was associated with a 12% increased risk for AF incidence (RR 1.12, 95% CI 1.06 to 1.18). The association was found to be apparent among new users (RR 1.53, 95% CI 1.37 to 1.70). The increased risk of AF might be explained by the occurrence of chronic heart failure and kidney disease. In addition, use of selective NSAIDs was still related to an increased risk of AF (RR 1.24, 95% CI 1.18 to 1.30). Sensitivity analyses found results to be robust. In conclusion, use of nonaspirin NSAIDs was associated with an increased risk of incident AF. The association was found to be apparent for new users, with a 53% increase in risk. These findings suggest that AF needs to be added to the cardiovascular risks to be considered when prescribing NSAIDs.

Effects of lipophilic statins for heart failure: a meta-analysis of 13 randomised controlled trials.

BACKGROUND: The effects of lipophilic statins in heart failure (HF) were controversial. The goal of the present study was to systematically review all randomised controlled trials evaluating the effects of lipophilic statins in patients with HF. METHODS: We performed a comprehensive literature search to identify eligible trials that prospectively randomised patients with HF to lipophilic statins or control. Primary end points were all-cause mortality, cardiovascular mortality, hospitalisation for worsening HF, left ventricular ejection fraction (LVEF), and low-density lipoprotein cholesterol. Risk ratios (RRs) and Weighted mean differences (WMDs) were calculated using fixed-effects models or random-effects models. RESULTS: A total of 13 randomised trials with 1,532 subjects were included in this analysis. Ten trials randomised patients to atorvastatin, two to simvastatin, and one to pitavastatin. Overall, lipophilic statins significantly decreased all-cause mortality (RR 0.53, P<0.001), cardiovascular mortality (RR 0.66, P=0.04), and hospitalisation for worsening HF (RR 0.60, P<0.001). Subgroup analyses showed that the effects of lipophilic statins in HF were not modified by age, baseline LVEF, and cause of HF. In addition, patients randomised to lipophilic statins had a significant increase in LVEF (WMD 3.91%, P<0.001) and decrease in low-density lipoprotein cholesterol (WMD 0.90 mmol/L, P<0.001). CONCLUSIONS: It appears that further studies are needed to determine if lipophilic statins are beneficial for HF patients.

Meta-analysis of the effect of statins on mortality in patients with preserved ejection fraction.

No therapy has been shown to improve survival rate in heart failure with preserved ejection fraction (HFPEF). Recent observational studies of the association between statin use and the risk of mortality in HFPEF have shown mixed results. The goal of the present study was to systematically review all published observational studies evaluating the effect of statins on the risk of mortality in HFPEF. A literature search in the PubMed and EMBASE databases was undertaken through December of 2013. Combined relative risk (RR) estimates and 95% confidence intervals (CIs) were calculated using the random-effects model. Subgroup analyses, sensitivity analysis, and cumulative meta-analysis were also performed. A total of 11 eligible studies with 17,985 patients with HFPEF were included in the analysis. Statin use was associated with a 40% lower risk of mortality (RR 0.60, 95% CI 0.49 to 0.74, p<0.001). Stratification of studies by controlled or uncontrolled confounding factors affected the final estimate (confounder-controlled RR 0.63, 95% CI 0.51 to 0.77, p<0.001 and confounder-uncontrolled RR 0.49, 95% CI 0.24 to 1.01, p=0.053). Furthermore, sensitivity analysis confirmed the stability of the results. Cumulative meta-analysis showed an obvious trend of reduction in mortality rates in statin users from 2005 to 2013. In conclusion, our meta-analysis supports the hypothesis that statin therapy may be associated with improved survival rates in patients with HFPEF. Nevertheless, randomized controlled trials are needed to confirm the efficacy of statins in HFPEF.