Early administration of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors in patients with acute coronary syndrome: a systematic review and meta-analysis.

BACKGROUND: High-intensity statin therapy is currently recommended initial guideline therapy in ACS treatment. However, only a minority of patients are achieving LDL-C attainment goal at 6 months. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are on recommended guideline therapy post-ACS if LDL-C goal attainment is not achieved after high-intensity statin (4-6 weeks) and after the addition of ezetimibe if guideline goal attainment is not achieved after an additional 4-6 weeks. Thus, it has been recommended that PCSK9 inhibitors be considered earlier post-ACS. However, the efficacy of early PCSK9 inhibitors initiation in ACS patients remains uncertain. METHODS: This systematic review and meta-analysis was conducted following PRISMA guidelines. Randomized controlled trials (RCTs) and observational studies involving ACS patients who received PCSK9 inhibitors within 48 h of hospitalization were included. Common and random effects models were used to evaluate the pooled effect of early PCSK9 inhibitor administration. Nine RCTs and three cohort studies were included. RESULTS: Early PCSK9 inhibitor administration reduced the incidence of MI, ACS hospitalization, and revascularization at 6-18 months post-ACS. Although there was a drift towards reduced stroke, all-cause mortality, and cardiovascular death, no statistically significant reduction was observed. Additionally, PCSK9 inhibitors significantly enhanced lipid control at 4-12 weeks after index hospitalization. CONCLUSION: Early PCSK9 inhibitors initiation in ACS patients reduces MACE and improves lipid profiles. While the results propose promising benefits in terms of stroke and mortality, further research with longer follow-up is required for more decisive evidence.

Oxidative balance score and associations with dyslipidemia and mortality among US adults: A mortality follow-up study of a cross-sectional cohort.

BACKGROUND: Oxidative stress has been implicated in the pathogenesis and progression of dyslipidemia. We aimed to investigate the association between the oxidative balance score, and dyslipidemia, as well as to assess the mortality risk associated with oxidative balance score in patients with dyslipidemia. METHODS: We performed a mortality follow-up study of a cross-sectional cohort of 26,118 adults from the National Health and Nutrition Examination Survey 1999-2018. The total oxidative balance score was calculated by 16 dietary nutrients (dietary oxidative balance score) and four lifestyle factors (lifestyle oxidative balance score). Weighted Cox proportional hazard model was applied to determine the relationship between oxidative balance score and all-cause or cardiovascular disease (CVD) mortality within the dyslipidemia group. RESULTS: During a median follow-up of 118 months, 2448 all-cause deaths (766 CVD-related) occurred. A significant negative correlation was observed between total oxidative balance score, dietary oxidative balance score, lifestyle oxidative balance score, and dyslipidemia. The multivariable-adjusted odds ratios and 95% CIs for dyslipidemia were 0.86 (0.77-0.97), 0.80 (0.72-0.91), and 0.63 (0.56-0.70), respectively, when comparing the second, third, and fourth quartiles of total oxidative balance score to the reference lowest quartile (P for trend <0.0001). Increasing total oxidative balance score was inversely associated with all-cause (hazard ratio [HR] = 0.98, 95% CI 0.98-0.99) and CVD-specific mortality (HR = 0.98, 95% CI 0.97-0.99) in participants with dyslipidemia. CONCLUSIONS: Oxidative balance score is inversely associated with dyslipidemia and linked to all-cause and CVD-related mortality, highlighting the potentially protective role of an antioxidant-rich diet against dyslipidemia.

Statin therapy and cardiovascular protection in type 2 diabetes: The role of baseline LDL-Cholesterol levels. A systematic review and meta-analysis of observational studies.

AIM: The guidelines recommend statins to prevent cardiovascular events in patients with type 2 diabetes (T2D) however, the importance of baseline LDL-Cholesterol (LDL-C) levels remains controversial. This study aimed to determine the association of statin use in T2D patients with major adverse cardiovascular events (MACE) and all-cause mortality and whether this association differs by baseline LDL-C levels. DATA SYNTHESIS: Medline, Embase, and Web of Science were systematically searched from inception until January 2022. Observational studies in patients with T2D comparing statin users vs non-users, with reports of the baseline LDL-C levels, were included. Random-effects meta-analysis and meta-regression were performed to estimate the overall effect on the risk of all-cause mortality and MACE (a composite of myocardial infarction, heart failure, stroke, and revascularization events) and the modification in the association by baseline LDL-C levels. We categorized studies according to their baseline LDL-C levels into 1) <100 mg/dl (2.59 mmol/l), 2) 100-130 mg/dl (2.59-3.37 mmol/l) and 3) >130 mg/dl (3.37 mmol/l) categories. A total of 9 cohort studies (n = 403,411 individuals) fulfilled our criteria. The follow-up duration ranged from 1.7 to 8 years. The overall combined estimate showed that statin therapy was associated with a significantly lower risk of MACE (Hazard Ratio (HR): 0.70 [95% CI 0.59 to 0.83], Absolute risk reduction percentage (ARR%): 3.19% [95%CI 0.88 to 5.50%) and all-cause mortality (HR: 0.60 [95% CI 0.46 to 0.79], ARR%: 5.23% [95% CI 2.18 to 8.28%), but varied, albeit not statistically significant, by baseline LDL-C levels. Studies with baseline LDL-C levels higher than 130 mg/dl had the greatest reduction of MACE (HR: 0.58 [95% CI 0.37 to 0.90]) and all-cause mortality risk (HR: 0.51 [95% CI [ 0.29 to 0.90]). The HRs of MACE in studies with LDL-C levels of 100-130 mg/dl and <100 mg/dl categories were respectively (0.70 [95% CI 0.59 to 0.83]) and (0.83 [95% CI [0.68 to 1.00]); and that of all-cause mortality were respectively (0.62 [95% CI 0.38 to 1.01]) and (0.67 [95% CI [0.44 to 1.02]). Statin use changes the HRs of MACE (0.99 [95%CI, 0.98 to 0.99]; P = 0.04) and all-cause mortality (0.99 [95% CI 0.98 to 1.01]; P = 0.8) per each mg/dl increase in baseline LDL-C level in meta-regression analyses. CONCLUSION: Statin therapy in patients with T2D was associated with reduced risk of MACE and all-cause mortality. Significant differences across studies with different baseline LDL-C levels were not observed.

Association between hyperuricemia and the risk of mortality in patients with osteoarthritis: A study based on the National Health and Nutrition Examination Survey database.

BACKGROUND: The purpose of this study was to evaluate the relationship between hyperuricemia and the risks of all-cause mortality and cardiovascular disease (CVD) mortality in patients with osteoarthritis (OA). METHODS: A retrospective cohort study was performed on 3,971 patients using data from the National Health and Nutrition Examination Survey database between 1999 and 2018. OA was diagnosed through specific questions and responses. The weighted COX regression models were used to explore the factors associated with all-cause mortality/CVD mortality in OA patients. Subgroup analyses were conducted based on age, gender, hypertension, dyslipidemia, CVD, and chronic kidney disease (CKD). Hazard ratio (HR) and 95% confidence interval (95% CI) were measured as the evaluation indexes. RESULTS: During the duration of follow-up time (116.38 ± 2.19 months), 33.69% (1,338 patients) experienced all-cause mortality, and 11.36% (451 patients) died from CVD. Hyperuricemia was associated with higher risks of all-cause mortality (HR: 1.22, 95% CI: 1.06-1.41, P = 0.008) and CVD mortality (HR: 1.32, 95% CI: 1.02-1.72, P = 0.036) in OA patients. Subgroup analyses showed that hyperuricemia was related to the risk of all-cause mortality in OA patients aged >65 years (HR: 1.17, 95% CI: 1.01-1.36, P = 0.042), in all male patients (HR: 1.41, 95% CI: 1.10-1.80, P = 0.006), those diagnosed with hypertension (HR: 1.17, 95% CI: 1.01-1.37, P = 0.049), dyslipidemia (HR: 1.18, 95% CI: 1.01-1.39, P = 0.041), CVD (HR: 1.30, 95% CI: 1.09-1.55, P = 0.004), and CKD (HR: 1.31, 95% CI: 1.01-1.70, P = 0.046). The association between hyperuricemia and a higher risk of CVD mortality was found in OA patients aged ≤ 65 years (HR: 1.90, 95% CI: 1.06-3.41, P = 0.032), who did not suffer from diabetes (HR: 1.36, 95% CI: 1.01-1.86, P = 0.048), who did not suffer from hypertension (HR: 2.56, 95% CI: 1.12-5.86, P = 0.026), and who did not suffer from dyslipidemia (HR: 2.39, 95% CI: 1.15-4.97, P = 0.020). CONCLUSION: These findings emphasize the importance of monitoring serum uric acid levels in OA patients for potentially reducing mortality associated with the disease.

Potential impact of blood cholesterol guidelines on statin treatment in the U.S. population using interrupted time series analysis.

BACKGROUND: The 2013 ACC/AHA Guideline was a paradigm shift in lipid management and identified the four statin-benefit groups. Many have studied the guideline's potential impact, but few have investigated its potential long-term impact on MACE. Furthermore, most studies also ignored the confounding effect from the earlier release of generic atorvastatin in Dec 2011. METHODS: To evaluate the potential (long-term) impact of the 2013 ACC/AHA Guideline release in Nov 2013 in the U.S., we investigated the association of the 2013 ACC/AHA Guideline with the trend changes in 5-Year MACE survival and three other statin-related outcomes (statin use, optimal statin use, and statin adherence) while controlling for generic atorvastatin availability using interrupted time series analysis, called the Chow's test. Specifically, we conducted a retrospective study using U.S. nationwide de-identified claims and electronic health records from Optum Labs Database Warehouse (OLDW) to follow the trends of 5-Year MACE survival and statin-related outcomes among four statin-benefit groups that were identified in the 2013 ACC/AHA Guideline. Then, Chow's test was used to discern trend changes between generic atorvastatin availability and guideline potential impact. RESULTS: 197,021 patients were included (ASCVD: 19,060; High-LDL: 33,907; Diabetes: 138,159; High-ASCVD-Risk: 5,895). After the guideline release, the long-term trend (slope) of 5-Year MACE Survival for the Diabetes group improved significantly (P = 0.002). Optimal statin use for the ASCVD group also showed immediate improvement (intercept) and long-term positive changes (slope) after the release (P < 0.001). Statin uses did not have significant trend changes and statin adherence remained unchanged in all statin-benefit groups. Although no other statistically significant trend changes were found, overall positive trend change or no changes were observed after the 2013 ACC/AHA Guideline release. CONCLUSIONS: The 2013 ACA/AHA Guideline release is associated with trend improvements in the long-term MACE Survival for Diabetes group and optimal statin use for ASCVD group. These significant associations might indicate a potential positive long-term impact of the 2013 ACA/AHA Guideline on better health outcomes for primary prevention groups and an immediate potential impact on statin prescribing behaviors in higher-at-risk groups. However, further investigation is required to confirm the causal effect of the 2013 ACA/AHA Guideline.

Association of Use and Dose of Lipid-Lowering Therapy Post Acute Myocardial Infarction With 5-Year Survival in Older Adults.

BACKGROUND: Older people are underrepresented in randomized trials. The association between lipid-lowering therapy (LLT) and its intensity after acute myocardial infarction and long-term mortality in this population deserves to be assessed. METHODS: The FAST-MI (French Registry of Acute ST-Elevation or Non-ST-Elevation Myocardial Infarction) program consists of nationwide French surveys including all patients admitted for acute myocardial infarction ≤48 hours from onset over a 1- to 2-month period in 2005, 2010, and 2015, with long-term follow-up. Numerous data were collected and a centralized 10-year follow-up was organized. The present analysis focused on the association between prescription of LLT (atorvastatin ≥40 mg or equivalent, or any combination of statin and ezetimibe) and 5-year mortality in patients aged ≥80 years discharged alive. Cox multivariable analysis and propensity score matching were used to adjust for baseline differences. RESULTS: Among the 2258 patients aged ≥80 years (mean age, 85±4 years; 51% women; 39% ST-segment elevation myocardial infarction; 58% with percutaneous coronary intervention), 415 were discharged without LLT (18%), 866 with conventional doses (38%), and 977 with high-dose LLT (43%). Five-year survival was 36%, 47.5%, and 58%, respectively. Compared with patients without LLT, high-dose LLT was significantly associated with lower 5-year mortality (adjusted hazard ratio, 0.78 [95% CI, 0.66-0.92]), whereas conventional-intensity LLT was not (adjusted hazard ratio, 0.93 [95% CI, 0.80-1.09]). In propensity score-matched cohorts (n=278 receiving high-intensity LLT and n=278 receiving no statins), 5-year survival was 52% with high-intensity LLT at discharge and 42% without statins (hazard ratio, 0.78 [95% CI, 0.62-0.98]). CONCLUSIONS: In these observational cohorts, high-intensity LLT at discharge after acute myocardial infarction was associated with reduced all-cause mortality at 5 years in an older adult population. These results suggest that high-intensity LLT should not be denied to patients on the basis of old age. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifiers: NCT00673036, NCT01237418, and NCT02566200.

Combination of low- or moderate-intensity statin and ezetimibe vs. high-intensity statin monotherapy on primary prevention of cardiovascular disease and all-cause death: a propensity-matched nationwide cohort study.

AIMS: This study aims to compare the preventive effect of low- or moderate-statin with ezetimibe combination therapy and high-intensity statin monotherapy on cardiovascular disease (CVD) and all-cause death in a real-world setting. METHODS AND RESULTS: Using the Korean National Health Insurance Service datasets, two cohorts comparing high-intensity statin monotherapy with low- or moderate-intensity statin and ezetimibe combination were constructed by 1:1 propensity score matching procedure. Primary outcome was a composite of myocardial infarction (MI), stroke, and all-cause death. Secondary outcome was an individual event. The study population was followed from baseline until the date of events, or the last health check-ups, whichever came first. Compared to high-intensity statin monotherapy, moderate-intensity statin with ezetimibe combination significantly reduced the risk of composite outcome [hazard ratio (HR) 0.84, 95% confidence interval (CI) 0.77-0.92, P < 0.001] as well as individual MI (HR 0.81, 95% CI 0.71-0.94, P = 0.005) and stroke (HR 0.78, 95% CI 0.65-0.93, P = 0.005), but not all-cause death. Low-intensity statin with ezetimibe also significantly reduced the risk of the composite outcomes (HR 0.80, 95% CI 0.66-0.97, P = 0.024) compared to high-intensity statin monotherapy, but the risk of individual outcome did not differ between two groups. Statin and ezetimibe combination demonstrated consistent effect across various subgroups. CONCLUSION: Among people without pre-existing CVD, moderate-intensity statin with ezetimibe combination was superior to high-intensity statin monotherapy in preventing composite outcomes as well as each of MI and stroke. In contrast, low-intensity statin with ezetimibe combination reduced the risk of composite but not individual outcomes.

We compared the preventive effect of low- or moderate-statin with ezetimibe combination and high-intensity statin monotherapy on cardiovascular disease and all-cause death. Low- or moderate-intensity statin with ezetimibe is beneficial for reducing a composite of myocardial infarction (MI), stroke, and all-cause death. Moderate-intensity statin with ezetimibe reduced 19% of MI and 22% of stroke, compared with high-intensity statin. Statin with ezetimibe combination might be attractive bypass for primary prevention, beyond an alternative to high-intensity statin.

Effect of blood lipid variability on mortality in patients with type 2 diabetes: a large single-center cohort study.

BACKGROUND: Dyslipidemia is a major cardiovascular risk factor and common in diabetes patients. Most guidelines focus on optimal lipid levels, while variation of lipid profiles is far less discussed. This study aims to investigate the association of visit-to-visit variability in blood lipids with all-cause, cardiovascular, and non-cardiovascular mortality in patients with type 2 diabetes. METHODS: We identified 10,583 type 2 diabetes patients aged ≥ 30 years with follow-up ≥ 3 years and who participated in the Diabetes Care Management Program at a medical center in Taiwan. Variability in lipid profiles within 3 years after entry was calculated using coefficient of variation. Cox proportional hazard models were used to evaluate lipid variability in relation to subsequent mortality. RESULTS: Over a mean follow-up of 6.4 years, 1838 all-cause deaths (809 cardiovascular deaths) were observed. For each 10% increase in variability in high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and total cholesterol, the hazard ratios (95% confidence intervals) of all-cause mortality were 1.30 (1.22-1.37), 1.05 (1.01-1.09), and 1.10 (1.03-1.16), respectively; those of cardiovascular mortality were 1.27 (1.16-1.39), 1.08 (1.02-1.15), and 1.16 (1.07-1.27), respectively. Each 10% increase in high-density lipoprotein cholesterol variability conveyed 31% greater risk of non-cardiovascular mortality. High variability in total cholesterol and low-density lipoprotein cholesterol increased all-cause mortality in subgroups of nonsmoking, regular exercising, non-dyslipidemia, and more severe status of diabetes at baseline. CONCLUSIONS: Blood lipid variability except for triglyceride variability was associated with all-cause and cardiovascular mortality in patients with type 2 diabetes.

Atherogenic index of plasma is associated with major adverse cardiovascular events in patients with type 2 diabetes mellitus.

BACKGROUND: Previous studies reported the prognostic value of the atherogenic index of plasma (AIP) in the course of atherosclerosis and other cardiovascular diseases (CVDs). Still, the predictive utility of the AIP is unknown among patients with type 2 diabetes mellitus (T2DM). METHODS: This was a secondary analysis of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study, which randomized 10,251 patients with long-lasting T2DM. ROC curve analysis was used to determine an optimal threshold for AIP, and the study population was divided into high and low AIP groups. Univariable and multivariable Cox proportional hazards regression analyses were used to determine the association between AIP and primary (major adverse cardiovascular events [MACEs], including nonfatal myocardial infarction, nonfatal stroke, and/or death from cardiovascular causes) and secondary outcomes (all-cause mortality). Stratified analyses were performed to control for the confounding factors. RESULTS: AIP was an independent risk factor for the prognosis of T2DM (HR = 1.309; 95% CI 1.084-1.581; P = 0.005). The threshold for AIP was determined to be 0.34 in the study population. After adjustments for confounding factors, multivariable analysis showed that AIP was associated with the risk of MACEs (Model 1: HR = 1.333, 95% CI 1.205-1.474, P < 0.001; Model 2: HR = 1.171, 95% CI 1.030-1.333, P = 0.016; Model 3: HR = 1.194, 95% CI 1.049-1.360, P = 0.007), all-cause mortality (Model 1: HR = 1.184, 95% CI 1.077-1.303, P < 0.001), cardiovascular death (Model 1: HR = 1.422, 95% CI 1.201-1.683, P < 0.001; Model 3: HR = 1.264, 95% CI 1.015-1.573, P = 0.036), and nonfatal myocardial infarction (Model 1: HR = 1.447, 95% CI 1.255-1.669, P < 0.001; Model 2: HR = 1.252, 95% CI 1.045-1.499, P = 0.015; Model 3: HR = 1.284, 95% CI 1.071-1.539, P = 0.007). Subgroup stratified analyses showed that AIP might interact with sex, a classical risk factor of cardiovascular events. CONCLUSIONS: This study showed that AIP might be a strong biomarker that could be used to predict the risk of cardiovascular events in patients with T2DM. TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov . Unique identifier: NCT00000620.

What Do US Physicians and Patients Think About Lipid-Lowering Therapy and Goals of Treatment? Results From the GOULD Registry.

Background Because of an increasing number and complexity of treatment options for lipid-lowering therapy in patients with atherosclerotic cardiovascular disease, guidelines recommend greater active involvement of patients in shared decision-making. However, patients' understanding and perceptions of the benefits, risks, and treatment objectives of lipid-lowering therapy are unknown. Methods and Results Structured questionnaires were conducted in 5006 US outpatients with atherosclerotic cardiovascular disease and suboptimal low-density lipoprotein cholesterol (LDL-C) control (LDL-C ≥70 mg/dL) or on a PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor and in 113 physician providers as a part of the GOULD (Getting to an Improved Understanding of Low-Density Lipoprotein Cholesterol and Dyslipidemia Management) Registry. Mean age of the patients was 68±10 years, 60% were men, and 86% were White race. Across all patients, 63% believed heart disease was the leading cause of death in men and 46% the leading cause of death in women. Only 28% of patients thought the primary reason they were taking lipid-lowering medication was to lower the risk of heart attack or stroke, 68% did not know their approximate LDL-C level, and 69% did not know their LDL-C goal. Patients on PCSK9 inhibitors (versus LDL-C cohort), younger patients (versus age ≥65 years), and men (versus women) were somewhat more knowledgeable about their disease and its management. Most physicians (66%) felt that a lack of understanding of the importance and efficacy of statins was the primary factor contributing to nonadherence, as opposed to costs (9%) or side effects (1%). More education was the most commonly used strategy to address patient-reported side effects. Conclusions A large proportion of patients with atherosclerotic cardiovascular disease remain unaware of their underlying atherosclerotic cardiovascular disease risk, reasons for taking lipid-lowering medications, current LDL-C levels, or treatment goals. These data highlight a large education gap which, if addressed, may improve shared decision-making and treatment adherence. Registration URL: https://www.clinicaltrials.org; Unique identifier: NCT02993120.

HDL-C, longitudinal change and risk of mortality in a Chinese cohort study.

BACKGROUND AND AIMS: High-density lipoprotein cholesterol (HDL-C) concentration and variability are both important factors of cardiovascular disease (CVD) and mortality. We aimed to explore the associations of HDL-C and longitudinal change in HDL-C with risk of mortality. METHODS AND RESULTS: We recruited a total of 69,163 participants aged ≥40 years and had medical examination records of HDL-C during 2010-2014 from the Yinzhou District, Ningbo, China. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression models. We observed a non-linear association of HDL-C with risks of non-accidental and CVD mortality. Compared with the moderate concentration group (1.4-1.6 mmol/L), HDL-C <1 mmol/L was associated with a higher risk of non-accidental mortality (HR: 1.13 (95% CI: 1.01-1.27)) and both HDL-C <1 mmol/L and ≥2 mmol/L were associated with a higher risk of CVD mortality (HRs: 1.23 (95% CI: 1.01-1.50) and 1.37 (95% CI: 1.03-1.82), respectively). Compared with the stable group ([-0.1, +0.1 mmol/L]), a large decrease ([-0.5, -0.3 mmol/L]) and very large decrease (<-0.5 mmol/L) in HDL-C were associated with a higher risk of non-accidental mortality (HRs: 1.40 (95% CI: 1.21-1.63) and 1.78 (95% CI: 1.44-2.20), respectively). Similar results were observed for CVD mortality and cancer mortality. CONCLUSION: Extremely low or high HDL-C and a large decrease or very large decrease in HDL-C were associated with a higher risk of cause-specific mortality. Monitoring of HDL-C may have utility in identifying individuals at higher risk of mortality.

Low-density lipoprotein cholesterol levels are associated with poor clinical outcomes in COVID-19.

BACKGROUND AND AIMS: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the sole causative agent of coronavirus infectious disease-19 (COVID-19). METHODS AND RESULTS: We performed a retrospective single-center study of consecutively admitted patients between March 1st and May 15th, 2020, with a definitive diagnosis of SARS-CoV-2 infection. The primary end-point was to evaluate the association of lipid markers with 30-days all-cause mortality in COVID-19. A total of 654 patients were enrolled, with an estimated 30-day mortality of 22.8% (149 patients). Non-survivors had lower total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-c) levels during the entire course of the disease. Both showed a significant inverse correlation with inflammatory markers and a positive correlation with lymphocyte count. In a multivariate analysis, LDL-c ≤ 69 mg/dl (hazard ratio [HR] 1.94; 95% confidence interval [CI] 1.14-3.31), C-reactive protein >88 mg/dl (HR 2.44; 95% CI, 1.41-4.23) and lymphopenia <1000 (HR 2.68; 95% CI, 1.91-3.78) at admission were independently associated with 30-day mortality. This association was maintained 7 days after admission. Survivors presented with complete normalization of their lipid profiles on short-term follow-up. CONCLUSION: Hypolipidemia in SARS-CoV-2 infection may be secondary to an immune-inflammatory response, with complete recovery in survivors. Low LDL-c serum levels are independently associated with higher 30-day mortality in COVID-19 patients.

Department of Veterans Affairs (VA) and U.S. Department of Defense (DoD) guidelines for management of dyslipidemia and cardiovascular disease risk reduction: Putting evidence in context.

Atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of morbidity and mortality in the United States (U.S.) and incurs significant cost to the healthcare system. Management of cholesterol remains central for ASCVD prevention and has been the focus of multiple national guidelines. In this review, we compare the American Heart Association (AHA)/American College of Cardiology (ACC) and the U.S. Department of Veterans Affairs (VA) and U.S. Department of Defense (DoD) Cholesterol guidelines. We review the evidence base that was used to generate recommendations focusing on 4 distinct themes: 1) the threshold of absolute 10-year ASCVD risk to start a clinician-patient discussion for the initiation of statin therapy in primary prevention patients; 2) the utility of coronary artery calcium score to guide clinician-patient risk discussion pertaining to the initiation of statin therapy for primary ASCVD prevention; 3) the use of moderate versus high-intensity statin therapy in patients with established ASCVD; and 4) the utility of ordering lipid panels after initiation or intensification of lipid lowering therapy to document efficacy and monitor adherence to lipid lowering therapy. We discuss why the VA/DoD and AHA/ACC may have reached different conclusions on these key issues.

Effects of Statin Therapy and Dose on Cardiovascular and Limb Outcomes in Peripheral Arterial Disease: A Systematic Review and Meta-analysis.

OBJECTIVE: Statin therapy is indicated in patients with peripheral arterial disease (PAD). National Institute for Health and Care Excellence guidelines suggest the use of "high intensity" statins, although evidence with PAD specific data are lacking. The effect of statin therapy and dose on outcomes in PAD is investigated. DATA SOURCES: Studies measuring statin use in PAD patients and outcomes were identified based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria. The EMBASE and MEDLINE databases were interrogated from January 1957 until February 2020. Twenty-two observational cohort studies and two randomised control trials were included (n = 268 611). REVIEW METHODS: Pooled estimates of dichotomous outcome data were calculated using the odds/hazard ratios (OR/HR) and 95% confidence interval (CI). Meta-analysis was conducted using the inverse variance or Mantel-Haenszel method. Outcomes included all cause mortality (ACM), cardiovascular mortality (CVM), major adverse cardiac events (MACE), and amputation. Subgroup analysis was performed on studies comparing patients taking high dose vs. combined low and moderate doses of statins. The GRADE criteria assessed the quality of evidence for outcomes. RESULTS: Statin therapy (vs. no statins) was significantly protective for ACM: OR 0.68 (95% CI 0.60 - 0.76) (number needed to treat [NNT] = 48), HR 0.74 (95% CI 0.70 - 0.78) (NNT = 10 - 91); MACE: OR 0.84 (95% CI 0.78 - 0.92) (NNT = 53), HR 0.78 (95% CI 0.65 - 0.93) (NNT = 167); and amputations: OR 0.59 (95% CI 0.33 - 1.07) (NNT = 333), HR 0.74 (95% CI 0.62 - 0.89) (NNT = 50). High doses of statins (vs. combined low and moderate doses) were significantly better protective against ACM OR 0.69 (95% CI 0.43 - 1.09) (NNT = 17), HR 0.74 (95% CI 0.62 - 0.89) (NNT = 16 - 200) but work less significantly for MACE OR 0.77 (95% CI 0.49 - 1.21) (NNT = 25). Amputations were less frequent in patients on high doses HR 0.78 (95% CI 0.69 - 0.90) (NNT = 53 - 1 000). CONCLUSION: Higher dosing of statins confers a significant improvement in patient outcomes, especially ACM and amputations, although the quality of the evidence was variable. Such findings require confirmation in larger, PAD specific trials.

Association of dyslipidemia with the severity and mortality of coronavirus disease 2019 (COVID-19): a meta-analysis.

BACKGROUND: The numbers of confirmed cases of coronavirus disease 2019 (COVID-19) and COVID-19 related deaths are still increasing, so it is very important to determine the risk factors of COVID-19. Dyslipidemia is a common complication in patients with COVID-19, but the association of dyslipidemia with the severity and mortality of COVID-19 is still unclear. The aim of this study is to analyze the potential association of dyslipidemia with the severity and mortality of COVID-19. METHODS: We searched the PubMed, Embase, MEDLINE, and Cochrane Library databases for all relevant studies up to August 24, 2020. All the articles published were retrieved without language restriction. All analysis was performed using Stata 13.1 software and Mantel-Haenszel formula with fixed effects models was used to compare the differences between studies. The Newcastle Ottawa scale was used to assess the quality of the included studies. RESULTS: Twenty-eight studies involving 12,995 COVID-19 patients were included in the meta-analysis, which was consisted of 26 cohort studies and 2 case-control studies. Dyslipidemia was associated with the severity of COVID-19 (odds ratio [OR] = 1.27, 95% confidence interval [CI] 1.11-1.44, P = 0.038, I2 = 39.8%). Further, patients with dyslipidemia had a 2.13-fold increased risk of death compared to patients without dyslipidemia (95% CI 1.84-2.47, P = 0.001, I2 = 66.4%). CONCLUSIONS: The results proved that dyslipidemia is associated with increased severity and mortality of COVID-19. Therefore, we should monitor blood lipids and administer active treatments in COVID-19 patients with dyslipidemia to reduce the severity and mortality.

Remnant Cholesterol and Cardiovascular Mortality in Patients With Type 2 Diabetes and Incident Diabetic Nephropathy.

CONTEXT: The association between remnant cholesterol (remnant-C) and cardiovascular mortality in patients with type 2 diabetes (T2D) and incident diabetic nephropathy remains unclear. OBJECTIVE: To examinie the association between remnant-C and cardiovascular mortality in patients with T2D, chronic kidney disease (CKD) stages 3 to 5, and newly diagnosed DN. METHODS: This study determined the baseline lipid profile and searched for deaths with cardiovascular disease (CVD) within 2 years of baseline among 2282 adults enrolled between January 1, 2015 and December 31, 2016, who had T2D, CKD stages 3 to 5, and newly diagnosed DN. Adjusted logistic regression models were used to assess the associations between lipid, especially remnant-C concentration (either as continuous or categorical variables), and risk of cardiovascular mortality. RESULTS: In multivariable-adjusted analyses, low-density lipoprotein cholesterol (LDL-C) (odds ratio [OR], 1.022; 95% CI, 1.017-1.026, per 10 mg/dL), high-density lipoprotein cholesterol (HDL-C) (OR, 0.929; 95% CI, 0.922-0.936, per 5 mg/dL), non-HDL-C (OR, 1.024; 95% CI, 1.021-1.028, per 10 mg/dL), and remnant-C (OR, 1.115; 95% CI, 1.103-1.127, per 10 mg/dL), but not triglycerides were associated with cardiovascular mortality. Atherogenic dyslipidemia (triglycerides > 150 mg/dL [1.69 mmol/L] and HDL-C < 40 mg/dL in men or < 50 mg/dL in women) was also associated with cardiovascular mortality (OR, 1.073; 95% CI, 1.031-1.116). Remnant-C greater than or equal to 30 mg/dL differentiated patients at a higher risk of cardiovascular mortality from those with lower concentrations, especially with interaction with LDL-C level greater than 100 mg/dL: The highest risk was found in patients with higher levels both of remnant-C and LDL-C (OR, 1.696; 95% CI, 1.613-1.783). CONCLUSION: In patients with T2D, CKD stages 3 to 5, and incident DN, remnant-C was associated with a higher risk of death with CVD. Different from the general population, the interaction of remnant-C and LDL-C was associated with the highest risk of cardiovascular mortality.

Compliance in Primary Prevention With Statins and Associations With Cardiovascular Risk and Death in a Low-Risk Population With Type 2 Diabetes Mellitus.

Background We examined whether primary prevention with statins and high adherence to statins reduce the associated risk of cardiovascular events or death in a low-risk population with type 2 diabetes mellitus (T2D). Methods and Results Using Danish nationwide registers, we included patients with new-onset T2D, aged 40 to 89 years, between 2005 and 2011, who were alive 18 months following the T2D diagnosis (index date). In patients who purchased statins within 6 months following T2D diagnosis, we calculated the proportion of days covered (PDC) within 1 year after the initial 6-month period. We studied the combined end point of myocardial infarction, stroke, or all-cause mortality, whichever came first, with Cox regression. Reported were standardized 5-year risk differences for fixed comorbidity distribution according to statin treatment history, stratified by sex and age. Among 77 170 patients, 42 975 (56%) were treated with statins, of whom 31 061 (72%) had a PDC ≥80%. In men aged 70 to 79 years who were treated with statins, the standardized 5-year risk was 22.9% (95% CI, 21.5%-24.3%), whereas the risk was 29.1% (95% CI, 27.4%-30.7%) in men not treated, resulting in a significant risk reduction of 6.2% (95% CI, 4.0%-8.4%), P<0.0001. The risk reduction associated with statins increased with advancing age group (women: age 40-49 years, 0.0% [95% CI, -1.0% to 1.0%]; age 80-89 years, 10.8% [95% CI, 7.2%-14.4%]). Standardizing to all patients treated with statins, PDC <80% was associated with increased risk difference (reference PDC ≥80%; PDC <20%, 4.2% [95% CI, 2.9%-5.6%]). Conclusions This study supports the use of statins as primary prevention against cardiovascular diseases or death in 18-month surviving low-risk patients with T2D, with the highest effect in the elderly and adherent patients.

Preadmission Statin Therapy and Clinical Outcome in Hospitalized Patients With COVID-19: An Italian Multicenter Observational Study.

ABSTRACT: Statin therapy has been recently suggested as possible adjuvant treatment to improve the clinical outcome in patients with coronavirus disease 2019 (COVID-19). The aim of this study was to describe the prevalence of preadmission statin therapy in hospitalized patients with COVID-19 and to investigate its potential association with acute distress respiratory syndrome (ARDS) at admission and in-hospital mortality. We retrospectively recruited 467 patients with laboratory-confirmed COVID-19 admitted to the emergency department of 10 Italian hospitals. The study population was divided in 2 groups according to the ARDS diagnosis at admission and in-hospital mortality. A multivariable regression analysis was performed to assess the risk of ARDS at admission and death during hospitalization among patients with COVID-19. A competing risk analysis in patients taking or not statins before admission was also performed. ARDS at admission was reported in 122 cases (26.1%). There was no statistically significant difference for clinical characteristics between patients presenting with and without ARDS. One hundred seven patients (18.5%) died during the hospitalization; they showed increased age (69.6 ± 13.1 vs. 66.1 ± 14.9; P = 0.001), coronary artery disease (23.4% vs. 12.8%; P = 0.012), and chronic kidney disease (20.6% vs. 11.1%; P = 0.018) prevalence; moreover, they presented more frequently ARDS at admission (48.6% vs. 19.4%; P < 0.001). At multivariable regression model, statin therapy was not associated neither with ARDS at admission nor with in-hospital mortality. Preadmission statin therapy does not seem to show a protective effect in severe forms of COVID-19 complicated by ARDS at presentation and rapidly evolving toward death.

Effects of Anthocyanins on Vascular Health.

Cardiovascular disorders are leading mortality causes worldwide, often with a latent evolution. Vascular health depends on endothelial function, arterial stiffness, and the presence of atherosclerotic plaques. Preventive medicine deserves special attention, focusing on modifiable cardiovascular risk factors, including diet. A diet rich in fruits and vegetables has well-known health benefits, especially due to its polyphenolic components. Anthocyanins, water-soluble flavonoid species, responsible for the red-blue color in plants and commonly found in berries, exert favorable effects on the endothelial function, oxidative stress, inhibit COX-1, and COX-2 enzymes, exert antiatherogenic, antihypertensive, antiglycation, antithrombotic, and anti-inflammatory activity, ameliorate dyslipidemia and arterial stiffness. The present review aims to give a current overview of the mechanisms involved in the vascular protective effect of anthocyanins from the human diet, considering epidemiological data, in vitro and in vivo preclinical research, clinical observational, retrospective, intervention and randomized studies, dietary and biomarker studies, and discussing preventive benefits of anthocyanins and future research directions.

Poor Metabolic Health Increases COVID-19-Related Mortality in the UK Biobank Sample.

Previous studies link obesity and components of metabolic health, such as hypertension or inflammation, to increased hospitalizations and mortality of patients with COVID-19. Here, in two overlapping samples of over 1,000 individuals from the UK Biobank we investigate whether metabolic health as measured by waist circumference, dyslipidemia, hypertension, type 2 diabetes, and systemic inflammation is related to increased COVID-19 infection and mortality rate. Using logistic regression and controlling for confounding variables such as socioeconomic status, age, sex or ethnicity, we find that individuals with worse metabolic health (measured on average eleven years prior to 2020) have an increased risk for COVID-19-related death (adjusted odds ratio: 1.75). We also find that specific factors contributing to increased mortality are increased serum glucose levels, systolic blood pressure and waist circumference.