Hyperlipidemia and mortality associated with diabetes mellitus co-existence in Chinese peritoneal dialysis patients.

BACKGROUND: To evaluate associations between diabetes mellitus (DM) coexisting with hyperlipidemia and mortality in peritoneal dialysis (PD) patients. METHODS: This was a retrospective cohort study with 2939 incident PD patients in China from January 2005 to December 2018. Associations between the DM coexisting with hyperlipidemia and mortality were evaluated using the Cox regression. RESULTS: Of 2939 patients, with a median age of 50.0 years, 519 (17.7%) died during the median of 35.1 months. DM coexisting with hyperlipidemia, DM, and hyperlipidemia were associated with 1.93 (95% CI 1.45 to 2.56), 1.86 (95% CI 1.49 to 2.32), and 0.90 (95% CI 0.66 to 1.24)-time higher risk of all-cause mortality, compared with without DM and hyperlipidemia, respectively (P for trend < 0.001). Subgroup analyses showed a similar pattern. Among DM patients, hyperlipidemia was as a high risk of mortality as non-hyperlipidemia (hazard ratio 1.02, 95%CI 0.73 to 1.43) during the overall follow-up period, but from 48-month follow-up onwards, hyperlipidemia patients had 3.60 (95%CI 1.62 to 8.01)-fold higher risk of all-cause mortality than those non-hyperlipidemia (P interaction = 1.000). CONCLUSIONS: PD patients with DM coexisting with hyperlipidemia were at the highest risk of all-cause mortality, followed by DM patients and hyperlipidemia patients, and hyperlipidemia may have an adverse effect on long-term survival in DM patients.

Association of hyperlipidaemia with 5-year survival after hospitalisation for acute myocardial infarction: a propensity score matched analysis.

Objectives: The primary objective was to examine the association between hyperlipidaemia (HLP) and 5-year survival after incident acute myocardial infarction (AMI). The secondary objectives were to assess the effect of HLP on survival to discharge across patient subgroups, and the impact of statin prescription, intensity and long-term statin adherence on 5-year survival. Methods: Retrospective cohort study of 7071 patients hospitalised for AMI at Mayo Clinic from 2001 through 2011. Of these, 2091 patients with HLP (age (mean±SD) 69.7±13.5) were propensity score matched to 2091 patients without HLP (age 70.6±14.2). Results: In matched patients, HLP was associated with higher rate of survival to discharge than no HLP (95% vs 91%; log-rank <0.0001). At year 5, the adjusted HR for all-cause mortality in patients with HLP versus no HLP was 0.66 (95% CI 0.58-0.74), and patients with prescription statin versus no statin was 0.24 (95% CI 0.21 to 0.28). The mean survival was 0.35 year greater in patients with HLP than in those with no HLP (95% CI 0.25 to 0.46). Patients with HLP gained on an average 0.17 life year and those treated with statin 0.67 life year at 5 years after AMI. The benefit of concurrent HLP was consistent across study subgroups. Conclusions: In patients with AMI, concomitant HLP was associated with increased survival and a net gain in life years, independent of survival benefit from statin therapy. The results also reaffirm the role of statin prescription, intensity and adherence in reducing the mortality after incident AMI.

Predictors of All-Cause Mortality after Endovascular Aneurysm Repair: Assessing the Role of Psoas Muscle Cross-Sectional Area.

PURPOSE: To evaluate psoas muscle area (PMA) as a predictor of all-cause mortality after endovascular aneurysm repair (EVAR) and compare it with other predictor variables. MATERIAL AND METHODS: Retrospective review of 407 patients who underwent EVAR over a 7-year period was performed. Demographics, comorbidity variables, and outcomes were collected. Preprocedure computed tomography scans were used to measure the PMA. Descriptive statistics summarized the demographic information and predictor variables. Kaplan-Meier analysis and univariate and multivariate Cox proportional regression analyses were performed. The main outcome measure was survival time. RESULTS: Median survival time for patients with PMA in the lowest quartile of the distribution (≤1442 mm2) was 65.5 months (95% confidence interval [95% CI] 37.7-78.9) vs 91.2 months (95% CI 77.9-110.0 when PMA >1442 mm2). Multivariate analysis revealed lower PMA was associated with decreased survival (adjusted hazard ratio [AHR] 1.68; 95% CI 1.15-2.40, P = .006). Similarly, the presence of coronary artery disease (AHR 1.54, 95% CI 1.01-2.35, P = .045) and statin use after EVAR were associated with decreased survival (AHR 2.36, 95% CI 1.24-4.49, P = .009). Hyperlipidemia was associated with increased survival after EVAR (AHR 0.51, 95% CI 0.33-0.81, P = .004). Compared with patients with low body mass index (BMI) (<18.5), a normal BMI was associated with increased survival (AHR 0.21, 95% CI 0.08-0.53, P = .001). CONCLUSIONS: Although PMA is a risk factor for decreased survival time, other factors such as patient hyperlipidemia, presence of coronary artery disease, post-EVAR statin use, and BMI are also predictive of postoperative mortality.

Lipoprotein(a) and Oxidized Phospholipids Promote Valve Calcification in Patients With Aortic Stenosis.

BACKGROUND: Lipoprotein(a) [Lp(a)], a major carrier of oxidized phospholipids (OxPL), is associated with an increased incidence of aortic stenosis (AS). However, it remains unclear whether elevated Lp(a) and OxPL drive disease progression and are therefore targets for therapeutic intervention. OBJECTIVES: This study investigated whether Lp(a) and OxPL on apolipoprotein B-100 (OxPL-apoB) levels are associated with disease activity, disease progression, and clinical events in AS patients, along with the mechanisms underlying any associations. METHODS: This study combined 2 prospective cohorts and measured Lp(a) and OxPL-apoB levels in patients with AS (Vmax >2.0 m/s), who underwent baseline 18F-sodium fluoride (18F-NaF) positron emission tomography (PET), repeat computed tomography calcium scoring, and repeat echocardiography. In vitro studies investigated the effects of Lp(a) and OxPL on valvular interstitial cells. RESULTS: Overall, 145 patients were studied (68% men; age 70.3 ± 9.9 years). On baseline positron emission tomography, patients in the top Lp(a) tertile had increased valve calcification activity compared with those in lower tertiles (n = 79; 18F-NaF tissue-to-background ratio of the most diseased segment: 2.16 vs. 1.97; p = 0.043). During follow-up, patients in the top Lp(a) tertile had increased progression of valvular computed tomography calcium score (n = 51; 309 AU/year [interquartile range: 142 to 483 AU/year] vs. 93 AU/year [interquartile range: 56 to 296 AU/year; p = 0.015), faster hemodynamic progression on echocardiography (n = 129; 0.23 ± 0.20 m/s/year vs. 0.14 ± 0.20 m/s/year] p = 0.019), and increased risk for aortic valve replacement and death (n = 145; hazard ratio: 1.87; 95% CI: 1.13 to 3.08; p = 0.014), compared with lower tertiles. Similar results were noted with OxPL-apoB. In vitro, Lp(a) induced osteogenic differentiation of valvular interstitial cells, mediated by OxPL and inhibited with the E06 monoclonal antibody against OxPL. CONCLUSIONS: In patients with AS, Lp(a) and OxPL drive valve calcification and disease progression. These findings suggest lowering Lp(a) or inactivating OxPL may slow AS progression and provide a rationale for clinical trials to test this hypothesis.

Association Between Total Cholesterol and 5 year Mortality in Patients with Carotid Artery Stenosis and Poststroke Functional Dependence.

BACKGROUND: Aggressive lipid-lowering treatment reduces the risk of cardiovascular events, but remains controversial in stroke patients. We investigate the influence of total cholesterol level on 5-year outcomes of ischemic stroke patients with high-grade internal carotid artery (ICA) stenosis and poststroke functional dependence. METHODS: One-hundred and ninety-six acute ischemic stroke patients with high-grade ICA stenosis and modified Rankin Scale score ≥ 3 upon discharge were enrolled and prospectively observed for 5 years. Patients were divided into 2 groups according to total cholesterol level at admission: ≥200 mg/dL or <200 mg/dL. Demographic features, vascular risk factors, co-morbidities, and outcomes were compared between the 2 groups. RESULTS: 117 (59.7%) patients had higher and 79 (40.3%) patients had lower total cholesterol levels. The prevalence of older age and atrial fibrillation was significantly higher in patients with lower total cholesterol; the prevalence of diabetes mellitus was higher in patients with higher total cholesterol. After adjusting for the established clinical predictors of adverse outcomes, the multivariate Cox regression revealed that lower total cholesterol level is a significant predictor of 5-year mortality (HR (hazard ratio) = 1.88, 95% CI (confidence interval) = 1.09-3.23, P = .023). CONCLUSIONS: Lower total cholesterol level is associated with increased risk of 5-year mortality in ischemic stroke patients with high-grade ICA stenosis and post-stroke functional dependence. Aggressive treatment of hyperlipidemia should be carefully considered in these patients although it could reduce the risk of atherosclerotic cardiovascular diseases and stroke recurrence in some stroke patients.

Relationships of Statin Therapy and Hyperlipidemia With the Incidence, Rupture, Postrepair Mortality, and All-Cause Mortality of Abdominal Aortic Aneurysm and Cerebral Aneurysm: A Meta-analysis and Systematic Review.

Statins have been suggested in previous studies to play a protective role in experimental cerebral aneurysm (CA) models; however, no evidence supports that the application of statins can protect against aneurysm rupture in humans, and the risks of lipid levels and aneurysms remain unknown. Therefore, this meta-analysis aimed to summarize and update the epidemiological evidence to systematically assess the relationships of statin therapy and hyperlipidemia with the incidence, rupture, postrepair mortality, and all-cause mortality of abdominal aortic aneurysm (AAA) and CA. Related studies were initially retrieved from the electronic databases PubMed, Embase, and Cochrane Library from inception to August 4, 2018. Subsequently, 33 studies were enrolled into this meta-analysis, and the maximum adjusted risk ratios (RRs) as well as the corresponding 95% confidence intervals were extracted. Finally, a total of 32 observational studies involving 150,134 participants were enrolled into this meta-analysis. The RRs of statin therapy for AAA incidence, AAA rupture, CA rupture, postrepair mortality, all-cause mortality, and adverse events were 1.83 (0.56-5.98), 0.67 (0.47-0.97), 0.50 (0.18-1.36), 0.60 (0.48-0.74), 0.66 (0.58-0.75), and 0.58 (0.47-0.71), respectively. Besides, the RR of hyperlipidemia for CA rupture was 0.79 (0.67-0.93). Our findings suggested that statin therapy could reduce the risks of AAA rupture, postrepair mortality, all-cause mortality, and adverse events, without inducing the risk of AAA incidence or CA rupture, and that hyperlipidemia was associated with a lower risk of CA rupture.

Metabolic factors affecting hepatocellular carcinoma in steatohepatitis.

BACKGROUND & AIMS: With the rising prevalence of alcoholism, obesity and metabolic syndrome, steatohepatitis will become the leading cause of end-stage liver disease and hepatocellular carcinoma in the United States by 2025. Patients with non-alcoholic steatohepatitis and alcoholic liver disease have similar clinical and histopathological presentations, whether these similarities persist in non-alcoholic steatohepatitis and alcoholic liver disease patients with hepatocellular carcinoma remains unknown. METHODS: A retrospective analysis of the clinical features of adult patients from a large transplant center who underwent liver transplantation for steatohepatitis due to non-alcoholic steatohepatitis and alcoholic causes (alcoholic liver disease) between 1/1/02 and 1/1/12 was performed. Clinical features, explant histopathology, and clinical outcomes were compared. RESULTS: Hepatocellular carcinoma was present in 80 of 317 patients, who underwent liver transplantation for steatohepatitis with equivalent distribution in non-alcoholic steatohepatitis and alcoholic liver disease patients (24% vs 26%; P = 0.8). On multivariate analysis, significant predictors of hepatocellular carcinoma included age, ethnicity (Hispanic), and diabetes, but not BMI, hypertension or smoking. A lower risk of hepatocellular carcinoma was associated with a clinical history of hyperlipidemia. Clinical parameters were similar between patients with alcoholic liver disease - hepatocellular carcinoma and non-alcoholic steatohepatitis-hepatocellular carcinoma, except sex and presence of metabolic syndrome. non-alcoholic steatohepatitis-hepatocellular carcinoma livers retained histopathological features of non-alcoholic steatohepatitis such as ballooning and Mallory bodies, while alcoholic liver disease-hepatocellular carcinoma livers did not. There were no significant differences in hepatocellular carcinoma recurrence rates or post-transplant overall survival. CONCLUSIONS: We report the largest single-center study evaluating clinical, histopathological and outcome measures of patients undergoing liver transplantation for steatohepatitis. Older patients, diabetics, and Hispanics may warrant more frequent cancer screening due to increased risk of hepatocellular carcinoma.

Strong Association Between Migraine and Transient Global Amnesia: A National Inpatient Sample Analysis.

The purpose of this article was to explore sex- and race-specific variables and comorbidities associated with transient global amnesia (TGA) using a nationally representative database. Data were obtained from the Nationwide Inpatient Sample using ICD-9 and procedure codes. Descriptive and survey logistic regression analyses were conducted and adjusted for influence of comorbidities, demographic characteristics, and hospitalization-related factors. Patients with migraines were 5.98 times more likely to also have a diagnosis of TGA compared with patients without migraines. Similarly, patients with TGA were more likely to have hypertension, precerebral disease, and hyperlipidemia. The odds of being diagnosed with TGA was lower among African Americans and Hispanics as well as among patients classified as Asian/Other, compared with Caucasians. TGA was associated with lower hospital charges ($14,242 versus $21,319), shorter hospital stays (mean days: 2.49 [SE=0.036] versus 4.72 [SE=0.025]), and routine hospital discharges (91.4% versus 74.5%). Patients with migraines and patients classified as Caucasian had higher odds of being diagnosed with TGA. All minority populations showed a lower rate of diagnosis that fell short of statistical significance.

Hypolipidemic and Hepatoprotective Effects of a Polyprenol-Containing Drug in Patients with Acute Coronary Syndrome.

In a double-blind placebo-controlled trial POLYNCOR (registration No. NCT03122340 at clinicaltrials.gov ), lipid-lowering and hepatoprotective effects of polyprenol-containing drug Ropren were evaluated in patients with acute coronary syndrome. After 2-months therapy, total cholesterol and ALT in the patients receiving Ropren were significantly (p<0.05) lower than in the control group. The number of patients who needed to discontinue or reduce the dose of atorvastatin due to an increase in the level of transaminases in the main group was significantly (p<0.05) lower than in the control group: 0 (0%) vs. 5 (33.3%). The more pronounced decrease in cholesterol level and hepatoprotective effect of Ropren allowed recommending this preparation to patients with acute coronary syndrome in addition to standard therapy.

Effect of hyperlipidemia on the incidence of cardio-cerebrovascular events in patients with type 2 diabetes.

BACKGROUND: This study was to explore the effect of hyperlipidemia on the incidence of cardio-cerebrovascular diseases in patients with type 2 diabetes. METHODS: Three hundred ninety five patients with type 2 diabetes in our hospital from January 2012 to January 2016 were followed up with an average of 3.8 years. The incidence of cardio-cerebrovascular diseases between diabetes combined with hyperlipidemia group (195 patients) and diabetes group (200 patients) were made a comparison. Multivariable Cox's proportional hazards regression model was used to analyze the effect of hyperlipidemia on the incidence of cardio-cerebrovascular diseases in patients with type 2 diabetes. RESULTS: Diastolic blood pressure, systolic blood pressure, high-density lipoprotein, low-density lipoprotein, body mass index and hyper-sensitive C-reactive protein were higher in diabetes combined with hyperlipidemia group than in diabetes group (P < 0.05). At the end of the follow-up period, all-cause mortality, cardio-cerebrovascular diseases mortality, and the incidence of myocardial infarction, cerebral infarction, cerebral hemorrhage and total cardiovascular events were significantly higher in diabetes combined with hyperlipidemia group than in diabetes group (P < 0.05). The analysis results of multivariable Cox's proportional hazards regression model showed that the risks of myocardial infarction and total cardiovascular events in diabetes combined with hyperlipidemia group were respectively 1.54 times (95%CI 1.13-2.07) and 1.68 times (95%CI 1.23-2.24) higher than those in diabetes group. Population attributable risk percent of all-cause mortality and total cardiovascular events in patients with type 2 diabetes combined with hyperlipidemia was 9.6% and 26.8%, respectively. CONCLUSIONS: Hyperlipidemia may promote vascular endothelial injury, increasing the risk of cardio-cerebrovascular diseases in patients with type 2 diabetes. Medical staffs should pay attention to the control of blood lipids in patients with type 2 diabetes to delay the occurrence of cardio-cerebrovascular diseases.

Influence of Prevalent and Incident Atrial Fibrillation on Post-Trial Major Events in ALLHAT.

AIMS: Limited information is available on long-term antihypertensive and lipid-lowering therapy effects on hypertensive patients with atrial fibrillation/flutter (AF/AFL) compared to those without. AF/AFL at baseline or during the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) (mean follow-up 4.9 years) markedly increased risk of stroke, heart failure, CHD, and all-cause mortality. We aimed to determine if AF/AFL continued to impact outcomes during post-trial follow-up (mean 3.8 years). METHODS: Patients were randomized to chlorthalidone, amlodipine, or lisinopril, and to pravastatin vs. usual care in the lipid-lowering trial (LLT). Of 31,473 available subjects, AF/AFL occurred in 854; 383/14,371 chlorthalidone (2.7%), 247/8565 amlodipine (2.9%), and 224/8537 lisinopril (2.6%). Post-hoc analyses utilized administrative databases for post-trial data. Individuals with AF/AFL were compared to those without during post-trial. Outcomes were analyzed by treatment groups for the antihypertensive and LLT trials. RESULTS: Among 854 AF/AFL participants, 491 (57.5%) died: 220 in-trial, 271 post-trial. Ten-year all-cause mortality rates for those with in-trial AF/AFL were similar for chlorthalidone and lisinopril, but lower for amlodipine (68, 66, and 49 per 100 persons, respectively); adjusted HR for amlodipine vs. chlorthalidone was 0.68 (95% CI, 0.54-0.87). Ten-year all-cause mortality rates were 57 vs. 65 per 100 persons (pravastatin vs. usual care); non-CVD mortality rates, 18 vs. 39 per 100 persons (pravastatin vs. usual care) (adjusted HR = 0.46, 95% CI, 0.24-0.86). CONCLUSION: Post-trial follow-up revealed continued deleterious AF/AFL effects. The amlodipine (ALLHAT) and pravastatin (ALLHAT-LLT) treatment groups showed lower all-cause and non-CVD mortality compared to the chlorthalidone and usual-care groups, respectively.

Long-Term Effects of Unprovoked Venous Thromboembolism on Mortality and Major Cardiovascular Events.

BACKGROUND: Patients with unprovoked venous thromboembolism (VTE) are at an increased risk of mortality, but whether their cardiovascular risks also increase remains to be determined. We aimed to investigate the factors associated with overall mortality and major adverse cardiovascular events in patients with unprovoked VTE. METHODS AND RESULTS: We identified 2154 patients newly diagnosed with unprovoked VTE from Taiwan's National Health Insurance Database between 2000 and 2013, excluding those with reversible etiologies, underlying cancer, or autoimmune diseases. These patients with VTE were compared with an age-, sex-, and cardiovascular risk-matched cohort of 4308 controls. The risk of mortality and major adverse cardiovascular events in patients with VTE was 2.23 (CI, 1.93-2.57; P<0.0001) and 1.86 (CI, 1.65-2.09; P<0.0001) times, respectively, higher than that of the conditions in controls. These events mostly occurred during the first year after the diagnosis of unprovoked VTE. Among patients with VTE, advanced age, male sex, and comorbid diabetes mellitus indicated a higher incidence of mortality and major adverse cardiovascular events. Conversely, comorbid hyperlipidemia attenuated these risks. CONCLUSIONS: This nation-wide cohort study revealed that patients with unprovoked VTE, particularly older males with diabetes mellitus, had an elevated risk of both mortality and cardiovascular events. Risk of mortality and major adverse cardiovascular events were highest within the first year after diagnosis and persisted during the 10 years of follow-up.

Statin use and all-cause and cancer mortality: BioBank Japan cohort.

BACKGROUND: Statins are the first-line agents used to treat patients with high serum low-density lipoprotein cholesterol levels, thus reducing the risk of death from arterial sclerotic cardiovascular disease; however, little is known about the effects of non-statin pharmacological interventions on mortality as well as about the potential protective effects of statin use against cancer death. This work aimed to compare all-cause and cancer mortality among patients with hyperlipidaemia who did and did not receive statin treatment. METHODS: Between 2003 and 2007 fiscal years, we recruited Japanese patients diagnosed with hyperlipidaemia from 66 hospitals. Patients in our cohort were followed up for a maximum of 12 years to observe the causes of death. Kaplan-Meier estimates from the baseline were used to compare the mortality of patients based on the administered medicine. All-cause mortality were compared among patients with/without administration of statins and other agents; any-organ and colorectal cancer mortality were compared between patients with/without administration of statins. RESULTS: Our cohort included 41,930 patients with mean ages of 64-66 years and mean body mass indices of 24-25 kg/m2. Patients who received statin monotherapy and were treated with lifestyle modification exhibited nearly identical survival curves, whereas statin use represented a non-significant but potentially protective effect against colorectal cancer-related mortality. The lowest mortality in this cohort was associated with resin monotherapy. CONCLUSIONS: Mortality rate has been similar for patients treated with statin monotherapy and lifestyle modification. Statin monotherapy could potentially reduce any-organ- and colorectal cancer-related mortality.

Impact of cigarette smoking on recurrence of hyperlipidemic acute pancreatitis.

AIM: To investigate the impact of cigarette smoking on the recurrence rate and recurrence-free survival in patients with hyperlipidemic acute pancreatitis (HLAP). METHODS: A total of 863 patients were admitted to our hospital for acute pancreatitis (AP) from January 2013 to March 2016, of whom 88 diagnosed with HLAP were enrolled in this retrospective study. Demographic data, medical history, previous episodes of pancreatitis, consumption of alcohol and cigarettes, as well as biochemical and hematological data were carefully recorded for univariate and multivariate analyses. During follow-up, the information on current smoking status and recurrent AP was gathered. Recurrence-free survival (RFS) was calculated using the Kaplan-Meier method, and the differences between groups were compared using the log-rank test. RESULTS: No significant differences were observed between the three groups in age or medical history of hyperlipidemia, fatty liver, diabetes mellitus, hypertension, or AP. The current smokers had a remarkably higher recurrence rate and a greater incidence of repeated episodes of AP (50.0% and 77.8%, respectively) than non-smokers (9.8% and 39.0%), and these two percentages were reduced to 9.1% and 36.4% for patients who gave up smoking. The median follow-up time was 13.5 mo and HLAP recurred after hospital discharge in 23 (26.1%) patients. Multivariate analysis identified current smoking (HR = 6.3, P = 0.020) as an independent risk factor contributing to HLAP recurrence. Current smokers had significantly worse RFS than non-smokers (23 mo vs 42 mo), but no significant difference was documented between ex-smokers (34 mo) and non-smokers. The RFS was not significantly different between light and heavy smokers. CONCLUSION: Smoking is associated with worse RFS and an increased rate of HLAP recurrence. Continued smoking correlates with a compromised survival and smoking cessation should be recommended.

Hyperlipidemia is associated with lower risk of poststroke mortality independent of statin use: A population-based study.

Background Although statin therapy is associated with reduced stroke and mortality risk, some studies report that higher lipid levels are associated with improved outcomes following ischemic stroke. Aims We examined the association of hyperlipidemia (HLD) combined with statin therapy on all-cause mortality in stroke patients. Methods All stroke patients in the Greater Cincinnati Northern Kentucky region of ∼1.3 million were identified using ICD-9 discharge codes in 2005 and 2010. Stroke patients with and without HLD were categorized based on their reported statin use at baseline or discharge into three groups: no-HLD/no-statins, HLD/no-statins, and HLD/on-statins. Cox proportional hazards model was used to estimate the risk of mortality at 30 days, 1 year, and 3 years poststroke. Results Overall, 77% (2953) of the 3813 ischemic stroke patients were diagnosed with HLD and 72% ( n = 2123) of those patients were on statin medications. The mean age was 70.0 ± 14.6 years, 56% were women, and 21% were black. In adjusted analyses, the HLD/no-statins group showed 35% (adjusted hazard ratio (aHR) = 0.65, 95% CI: 0.46-0.92), 27% (aHR = 0.73, 95% CI: 0.59-0.90), and 17% (aHR = 0.83, 95% CI: 0.70-0.97) reduced risk of mortality at 30 days, 1 year, and 3 years, respectively, poststroke, compared with no-HLD/no-statins group. The HLD/on-statins group showed an additional 17% significant survival benefit at 3 years poststroke compared with HLD/no-statins group. Conclusions A diagnosis of HLD in ischemic stroke patients is associated with reduced short- and long-term mortality, irrespective of statin use. Statin therapy is associated with significant, additional long-term survival benefit.

Ezetimibe-Statin Combination Therapy.

BACKGROUND: To date, most clinical comparisons of ezetimibe-statin combination therapy versus statin monotherapy have relied entirely on surrogate variables. In this systematic review, we study the efficacy and safety of ezetimibe-statin combination therapy in comparison to statin monotherapy in terms of the prevention of cardiovascular events in hyperlipidemic patients with atherosclerosis and/or diabetes mellitus. METHODS: This review is based on a systematic literature search (1995 to July 2015) in PubMed, the Excerpta Medica Database (EMBASE), the Cochrane Library, and the ClinicalTrials.gov registry. RESULTS: Nine randomized, controlled trials with data from a total of 19 461 patients were included. Ezetimibe-statin combination therapy was associated with a lower risk of cardiovascular events than statin monotherapy: 33% of the patients treated with ezetimibe and a statin, and 35% of those treated with a statin alone, had a cardiovascular event within seven years (number needed to treat [NNT]: 50 over 7 years). Combination therapy was also significantly more effective in preventing a composite endpoint consisting of death due to cardiovascular disease, nonfatal myocardial infarction, unstable angina pectoris, coronary revascularization, and nonfatal stroke (hazard ratio [HR] 0.94, 95% confidence interval [0,89; 0,99]; p = 0.016). Diabetic patients benefited from combination therapy rather than monotherapy with respect to cardiovascular morbidity (HR 0.87 [0.78; 0.94]). On the other hand, the addition of ezetimibe to statin therapy did not lessen either cardiovascular or overall mortality. Serious undesired events occurred in 38% of the patients taking ezetimibe and a statin nd in 39% of the patients taking a statin alone (relative risk 1.09 [0.77; 1.55]). CONCLUSION: In high-risk patients with an acute coronary syndrome, combination therapy with ezetimibe and a statin lowered the risk of cardiovascular events in comparison to statin monotherapy. The risk of dying or suffering an adverse drug effect was similar in the two treatment groups.

Disruption of Slc52a3 gene causes neonatal lethality with riboflavin deficiency in mice.

Homeostasis of riboflavin should be maintained by transporters. Previous in vitro studies have elucidated basic information about riboflavin transporter RFVT3 encoded by SLC52A3 gene. However, the contribution of RFVT3 to the maintenance of riboflavin homeostasis and the significance in vivo remain unclear. Here, we investigated the physiological role of RFVT3 using Slc52a3 knockout (Slc52a3-/-) mice. Most Slc52a3-/- mice died with hyperlipidemia and hypoglycemia within 48 hr after birth. The plasma and tissue riboflavin concentrations in Slc52a3-/- mice at postnatal day 0 were dramatically lower than those in wild-type (WT) littermates. Slc52a3-/- fetuses showed a lower capacity of placental riboflavin transport compared with WT fetuses. Riboflavin supplement during pregnancy and after birth reduced neonatal death and metabolic disorders. To our knowledge, this is the first report to indicate that Rfvt3 contributes to placental riboflavin transport, and that disruption of Slc52a3 gene caused neonatal mortality with hyperlipidemia and hypoglycemia owing to riboflavin deficiency.