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.

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.

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.

The cost-effectiveness of intensive low-density lipoprotein cholesterol lowering in people with peripheral artery disease.

BACKGROUND: People with peripheral artery disease are at a high risk of major adverse cardiovascular events (MACE) and major adverse limb events (MALE). Randomized controlled trials suggest that intensive lowering of low-density lipoprotein cholesterol (LDL-C) with proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors is an effective strategy to prevent these events. This study estimated the potential benefit and cost-effectiveness of administrating PCSK9 inhibitors to a cohort of participants with peripheral artery disease. METHODS: A total of 783 participants with intermittent claudication (IC; n = 582) or chronic limb-threatening ischemia (CLTI; n = 201) were prospectively recruited from three hospitals in Australia. Serum LDL-C was measured at recruitment, and the occurrence of MACE and MALE was recorded over a median (interquartile range) follow-up of 2.2 years (0.3-5.7 years). The potential benefit of administering a PCSK9 inhibitor was estimated by calculating the absolute risk reduction and numbers needed to treat (NNT) based on relative risk reductions reported in published randomized trials. The incremental cost-effectiveness ratio per quality-adjusted life year gained was estimated. RESULTS: Intensive LDL-C lowering was estimated to lead to an absolute risk reduction in MACE of 6.1% (95% confidence interval [CI], 2.0-9.3; NNT, 16) and MALE of 13.7% (95% CI, 4.3-21.5; NNT, 7) in people with CLTI compared with 3.2% (95% CI, 1.1-4.8; NNT, 32) and 5.3% (95% CI, 1.7-8.3; NNT, 19) in people with IC. The estimated incremental cost-effectiveness ratios over a 10-year period were $55,270 USD and $32,800 USD for participants with IC and CLTI, respectively. CONCLUSIONS: This analysis suggests that treatment with a PCSK9 inhibitor is likely to be cost-effective in people with CLTI.

Statin adherence and risk of all-cause, cancer, and cardiovascular mortality among dyslipidemia patients: A time-dependent analysis.

BACKGROUND AND AIM: Results have been mixed and uncertainty still remains regarding the impact of statin adherence on premature deaths. Thus, we investigated the association between statin adherence and risks of all-cause, cancer, and cardiovascular mortality among dyslipidemia patients in South Korea. METHODS AND RESULTS: We used data from the National Health Insurance Service (NHIS) National Sample Cohort for the years 2003-2013, which included data on 107,954 middle-aged and elderly dyslipidemia patients. Among these patients, a time-dependent Cox proportional hazards model was used to estimate the hazard ratios (HRs) of all-cause, cancer, and cardiovascular mortality depending on proportion of days covered (PDC) by statin medication. A total of 3073 (2.85%) individuals died within the study period. Of these individuals, 1143 (1.06%) died from cancer, and 687 (0.64%) died from cardiovascular diseases. Relative to good medication adherence (>80%), moderate (50-80%) (hazard ratio [HR]: 1.28, 95% confidence interval [CI]: 1.14-1.43) and poor (<50%) (HR: 1.58, 95% CI: 1.41-1.78) adherence were associated with increased risk of all-cause mortality. Poor adherence was also associated with increased risk of cancer (HR: 1.33, 95% CI: 1.16-1.52) and cardiovascular (HR: 1.27, 95% CI: 1.06-1.51) mortality. CONCLUSION: Such findings reveal that relative to good statin adherence, moderate and/poor adherence is associated with increased risks of all-cause, cancer, and cardiovascular mortality. Clinicians should assess for dyslipidemia, link statin adherence problems to potential mortality risk, and monitor outcomes in both medication adherence and disease complications.

Triglyceride to high-density lipoprotein cholesterol ratio and risk of atherosclerotic cardiovascular disease in a Chinese population.

BACKGROUND AND AIMS: Triglyceride (TG) to high-density lipoprotein cholesterol (HDL-C) ratio may play a role in predicting cardiovascular events. We aimed to prospectively explore the association between the TG/HDL-C ratio and atherosclerotic cardiovascular disease (ASCVD), ischemic stroke, as well as coronary heart disease (CHD) in a Chinese population. METHODS AND RESULTS: This prospective cohort study included 9368 participants from four Chinese populations in the People's Republic of China-United States of America (PRC-USA) Collaborative Study of Cardiovascular and Cardiopulmonary Epidemiology. Over a follow-up period of 20 years, 624 cases of ASCVD events including 458 ischemic stroke events and 166 CHD events were recorded. The relationship between the TG/HDL-C ratio and the endpoints was evaluated through multivariate Cox proportional hazard models adjusted for potential confounding variables, including age, sex, urban or rural residence, northern or southern China, occupational type, education, physical exercise, smoking status, drinking status, body mass index, hypertension, high low-density lipoprotein cholesterol, diabetes, and antihypertensive medication use at baseline. With the lowest TG/HDL-C tertile as the reference, the middle and highest tertiles had the hazard ratios (HRs) and 95% confidence intervals (CIs) of 1.13 (0.91, 1.40), 1.36 (1.10, 1.67) respectively for ASCVD (p for trend = 0.0028), and 1.19 (0.93, 1.54),1.47 (1.15, 1.87) respectively for ischemic stroke (p for trend = 0.0016). However, no significant association was found for CHD events. CONCLUSION: TG/HDL-C ratio was positively associated with the risk of ASCVD and ischemic stroke events in the Chinese population.

Lipid-lowering nutraceuticals update on scientific evidence.

: Cardiovascular diseases (CVDs) are the main cause of mortality worldwide. Risk factors of CVD can be classified into modifiable (smoking, hypertension, diabetes, hypercholesterolemia) through lifestyle changes or taking drug therapy and not modifiable (age, ethnicity, sex and family history). Elevated total cholesterol (TC) and low-density lipoprotein-cholesterol (LDL-C) levels have a lead role in the development of coronary heart disease (CHD), while high levels of high-density lipoprotein-cholesterol (HDL-C) seem to have a protective role.The current treatment for dyslipidemia consists of lifestyle modification or drug therapy even if not pharmacological treatment should be always considered in addition to lipid-lowering medications.The use of lipid-lowering nutraceuticals alone or in association with drug therapy may be considered when the atherogenic cholesterol goal was not achieved.These substances can be classified according to their mechanisms of action into natural inhibitors of intestinal cholesterol absorption, inhibitors of hepatic cholesterol synthesis and enhancers of the excretion of LDL-C. Nevertheless, many of them are characterized by mixed or unclear mechanisms of action.The use of these nutraceuticals is suggested in individuals with borderline lipid profile levels or with drug intolerance, but cannot replace standard lipid-lowering treatment in patients at high, or very high CVD risk.Nutraceuticals can also have vascular effects, including improvement in endothelial dysfunction and arterial stiffness, as well as antioxidative properties. Moreover, epidemiological and clinical studies reported that in patients intolerant of statins, many nutraceuticals with demonstrated hypolipidemic effect are well tolerated.

A Randomized Clinical Trial of the Efficacy and Safety of Interferon ß-1a in Treatment of Severe COVID-19.

To the best of our knowledge, there is no published study on the use of interferon ß-1a (IFN ß-1a) in the treatment of severe COVID-19. In this randomized clinical trial, the efficacy and safety of IFN ß-1a were evaluated in patients with severe COVID-19. Forty-two patients in the interferon group received IFN ß-1a in addition to the national protocol medications (hydroxychloroquine plus lopinavir-ritonavir or atazanavir-ritonavir). Each 44-µg/ml (12 million IU/ml) dose of interferon ß-1a was subcutaneously injected three times weekly for two consecutive weeks. The control group consisted of 39 patients who received only the national protocol medications. The primary outcome of the study was time to reach clinical response. Secondary outcomes were duration of hospital stay, length of intensive care unit stay, 28-day mortality, effect of early or late administration of IFN on mortality, adverse effects, and complications during the hospitalization. Between 29 February and 3 April 2020, 92 patients were recruited, and a total of 42 patients in the IFN group and 39 patients in the control group completed the study. As the primary outcome, time to the clinical response was not significantly different between the IFN and the control groups (9.7 ± 5.8 versus 8.3 ± 4.9 days, respectively, P = 0.95). On day 14, 66.7% versus 43.6% of patients in the IFN group and the control group, respectively, were discharged (odds ratio [OR], 2.5; 95% confidence interval [CI], 1.05 to 6.37). The 28-day overall mortality was significantly lower in the IFN than the control group (19% versus 43.6%, respectively, P = 0.015). Early administration significantly reduced mortality (OR, 13.5; 95% CI, 1.5 to 118). Although IFN did not change the time to reach the clinical response, adding it to the national protocol significantly increased discharge rate on day 14 and decreased 28-day mortality. (This study is in the Iranian Registry of Clinical Trials under identifier IRCT20100228003449N28.).

A Retrospective Controlled Cohort Study of the Impact of Glucocorticoid Treatment in SARS-CoV-2 Infection Mortality.

Evidence to support the use of steroids in coronavirus disease 2019 (COVID-19) pneumonia is lacking. We aim to determine the impact of steroid use for COVID-19 pneumonia on hospital mortality. We performed a single-center retrospective cohort study in a university hospital in Madrid, Spain, during March of 2020. To determine the role of steroids in in-hospital mortality, patients admitted with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia and treated with steroids were compared to patients not treated with steroids, and we adjusted with a propensity score for patients on steroid treatment. Survival times were compared using the log rank test. Different steroid regimens were compared and adjusted with a second propensity score. During the study period, 463 out of 848 hospitalized patients with COVID-19 pneumonia fulfilled inclusion criteria. Among them, 396 (46.7%) patients were treated with steroids and 67 patients were not. Global mortality was 15.1%. The median time to steroid treatment from symptom onset was 10 days (interquartile range [IQR], 8 to 13 days). In-hospital mortality was lower in patients treated with steroids than in controls (13.9% [55/396] versus 23.9% [16/67]; hazard ratio [HR], 0.51 [95% confidence interval, 0.27 to 0.96]; P = 0.044). Steroid treatment reduced mortality by 41.8% relative to the mortality with no steroid treatment (relative risk reduction, 0.42 [95% confidence interval, 0.048 to 0.65]). Initial treatment with 1 mg/kg of body weight/day of methylprednisolone versus steroid pulses was not associated with in-hospital mortality (13.5% [42/310] versus 15.1% [13/86]; odds ratio [OR], 0.880 [95% confidence interval, 0.449 to 1.726]; P = 0.710). Our results show that the survival of patients with SARS-CoV-2 pneumonia is higher in patients treated with glucocorticoids than in those not treated. Rates of in-hospital mortality were not different between initial regimens of 1 mg/kg/day of methylprednisolone and glucocorticoid pulses.

Bayesian credible subgroup identification for treatment effectiveness in time-to-event data.

Due to differential treatment responses of patients to pharmacotherapy, drug development and practice in medicine are concerned with personalized medicine, which includes identifying subgroups of population that exhibit differential treatment effect. For time-to-event data, available methods only focus on detecting and testing treatment-by-covariate interactions and may not consider multiplicity. In this work, we introduce the Bayesian credible subgroups approach for time-to-event endpoints. It provides two bounding subgroups for the true benefiting subgroup: one which is likely to be contained by the benefiting subgroup and one which is likely to contain the benefiting subgroup. A personalized treatment effect is estimated by two common measures of survival time: the hazard ratio and restricted mean survival time. We apply the method to identify benefiting subgroups in a case study of prostate carcinoma patients and a simulated large clinical dataset.

Interplay of Coronary Artery Calcium and Risk Factors for Predicting CVD/CHD Mortality: The CAC Consortium.

OBJECTIVES: This study sought to evaluate the association and burden of coronary artery calcium (CAC) with long-term, cause-specific mortality across the spectrum of baseline risk. BACKGROUND: Although CAC is a known predictor of short-term, all-cause mortality, data on long-term and cause-specific mortality are inadequate. METHODS: The CAC Consortium cohort is a multicenter cohort of 66,636 participants without coronary heart disease (CHD) who underwent CAC testing. The following risk factors (RFs) were considered: 1) current cigarette smoking; 2) dyslipidemia; 3) diabetes mellitus; 4) hypertension; and 5) family history of CHD. RESULTS: During the 12.5-years median follow-up, 3,158 (4.7%) deaths occurred; 32% were cardiovascular disease (CVD) deaths. Participants with CAC scores ≥400 had a significantly increased risk for CHD and CVD mortality (hazard ratio [HR]: 5.44; 95% confidence interval [CI]: 3.88 to 7.62; and HR: 4.15; 95% CI: 3.29 to 5.22, respectively) compared with CAC of 0. Participants with ≥3 RFs had a smaller increased risk for CHD and CVD mortality (HR: 2.09; 95% CI: 1.52 to 2.85; and HR: 1.84; 95% CI: 1.46 to 2.31, respectively) compared with those without RFs. Across RF strata, CAC added prognostic information. For example, participants without RFs but with CAC ≥400 had significantly higher all-cause, non-CVD, CVD, and CHD mortality rates compared with participants with ≥3 RFs and CAC of 0. CONCLUSIONS: Across the spectrum of RF burden, a higher CAC score was strongly associated with long-term, all-cause mortality and a greater proportion of deaths due to CVD and CHD. Absence of CAC identified people with a low risk over 12 years of follow-up, with most deaths being non-CVD in nature, regardless of RF burden.

Three-year outcomes related to coronary stenting; a registry-based real-life population study.

Objectives. Developments in medication and coronary interventions have improved coronary artery disease (CAD) treatment. We studied long-term outcomes in an observational, real-life population of CAD patients undergoing percutaneous coronary intervention (PCI) depending on the presentation and the stent type used. Design and results. Register included 789 consecutive patients undergoing PCI. Follow up period was three years with primary composite outcome (MACE) of all cause -mortality, myocardial infarction and target lesion revascularization. Mean age was 65 ± 11 and 69% were male. New-generation drug-eluting stents (DES-2) were associated with lower adjusted rates of MACE (HR 0.47; 95% CI 0.29-0.77) but not mortality (HR 0.50; 95% CI 0.22-1.14) in comparison to bare-metal stents. Patients with STEMI (14.4%) or NSTEMI (13.7%) had higher crude mortality rates than those with unstable (4.5%) or stable CAD (3.1%; p < .001). The association diminished after adjustments in NSTEMI (HR 2.01; 95% CI 0.88-4.58). Among smokers 45% quitted and 36% achieved recommended cholesterol levels. Conclusions. The overall prognosis was good. Irrespective of comorbidities, NSTEMI was not associated with worse outcome than stable CAD. DES-2 was associated with lower rates of MACE than BMS without affecting mortality rate. Patients succeeded better in smoking cessation than reaching recommended cholesterol levels.

Intervención educativa para la prevención de complicaciones en pacientes con dislipidemia / Educational intervention for the prevention of complications in patients with dyslipidemia

RESUMEN Introducción: actualmente, la enfermedad ateroesclerótica está entre las principales causas de muerte, incapacidad y demencia en adultos mayores. Su causalidad es multifactorial, pero es indiscutible la relación de la dislipidemia con los riesgos de eventos cardiovasculares. Objetivo: dotar de información necesaria a pacientes, para modificar estilos de vida y lograr un impacto positivo en la reducción de la morbimortalidad, producida por enfermedades ateroescleróticas. Materiales y métodos: se aplicó un proyecto de intervención a través de acciones educativas a un grupo de pacientes adultos (n=234) con dislipidemia. Atendidos en la Unidad de Salud Oziel Montecristo, por el equipo I (blanco) del municipio de Campinas, Departamento de São Paulo. Entre enero a julio del 2016. Los participantes fueron sometidos a una encuesta antes y después de recibir la información. Resultados: el grupo etáreo que predominó fue entre 20-50 años con 55,5 %. La escolaridad primaria fue más significativa en el 41 %. Otros factores de riesgo reportados fue obesidad, 46,5 %; fumadores, 9,4 %; con etilismo crónico, 8,5 % y sedentarismo 71,7 %. Las enfermedades crónicas presentes fueron: hipertensión arterial, 53,4 %; diabetes mellitus, 40,5 %; cardiopatía isquémica y enfermedad renal crónica el 20,9 % y 9,4 %, respectivamente. Se lograron resultados positivos en el auditorio, un número importante de pacientes continuaron en los grupos terapéuticos. Conclusiones: los pacientes se apropiaron de conocimientos importantes sobre la dislipidemia, para practicar estilos de vida saludables, que disminuyan el riesgo de eventos cardiovasculares (AU).

ABSTRACT Introduction: currently, atherosclerotic disease is among the main causes of death, disability and dementia in elder people. It is caused by multiple factors, but it is indisputable the relation of dyslipidemia with the risk of cardiovascular events. Objective: to provide the necessary information to patients for them to modify life styles and achieving a positive impact in the reduction of the morbidity and mortality caused by atherosclerotic diseases. Materials and methods: an intervention project was applied through educative actions in a group of adult patients (n=234) with dyslipidemia, treated in the Health Unit ¨Oziel Montecristo¨, by the team I (white), of the municipality Campinas, São Paulo Department, from January to July 2016. The participants answered an inquiry before and after receiving the information. Results: the predominant age group was the 20-50 years one, with 55.5 %. Primary scholarship was the most significant (41 %). Other reported factors were obesity, 46.5 %; smoking, 9.4 %; chronic alcoholism, 8.5 %; and sedentary life style, 71.7 %. The chronic diseases found were: arterial hypertension, 53.4 %; diabetes mellitus, 40.5 %; ischemic heart disease, 20.9 %; and chronic renal disease, 9.4 %. Positive results were achieved in the audience; an important number of patients continued in therapeutic groups. Conclusions: the patients assimilated important knowledge on dyslipidemia, to practice healthy life styles decreasing the risk of cardiovascular events (AU).

Comorbidity burden in systemic sclerosis: beyond disease-specific complications.

Systemic sclerosis (SSc) is a chronic, systemic disease characterized by fibrosis of the skin and internal organs, vasculopathy, and auto-immune activation. On the top of severe organ involvement such as interstitial lung and myocardial fibrosis, pulmonary hypertension, and renal crisis, individuals diagnosed with SSc may suffer from a number of comorbidities. This is a narrative review according to published recommendations and we searched the online databases MEDLINE and EMBASE using as key words the following terms: systemic sclerosis, scleroderma, myocardial fibrosis in combination with micro- and macro-vascular disease, cardiac involvement, atherosclerosis, cardiovascular disease and coronary arteries, infections, cancer, depression, osteoporosis, and dyslipidemia. Although data are usually inconclusive it appears that comorbidities with significant impact on life expectancy, namely cardiovascular disease, infections, and cancer as well as phycological disorders affecting emotional and mental health are highly prevalent in SSc population. Thereafter, the aim of this review is to summarize the occurrence and the clinical significance of such comorbidities in SSc population and to discuss how rheumatologists can incorporate the management of these conditions in daily clinical practice.

Association between plasma lipid levels during acute coronary syndrome and long-term malignancy risk. The ABC-4* study on heart disease.

BACKGROUND: Emerging evidence suggests that patients with coronary artery disease carry an increased risk of developing malignancy, with deleterious effects on long-term prognosis. Our aim was to ascertain whether baseline plasma lipid levels during acute coronary syndrome (ACS) are associated with malignancy in long-term. METHODS: This study included 589 patients admitted with ACS to three centers and discharged alive. Plasma lipid levels were assessed on the first morning after admission. Patients were followed for 17 years or until death. RESULTS: Five hundred seventy-one patients were free from malignancy at enrollment, of them 99 (17.3%) developed the disease during follow-up and 75 (13.1%) died due to it. Compared to patients without malignancy, those with malignancy showed lower plasma levels of total cholesterol (TC), low-density lipoprotein (LDL), and triglycerides (TG). The groups showed similar statin use rates at any time in follow-up. The incidence rate of neoplasia and neoplastic mortality was higher in patients with baseline TC or LDL values ≤ median; they showed 85 and 72% increased incidence rate of developing malignancy and 133 and 122% increased incidence rate of neoplastic death respectively. No differences were observed relative to HDL and TG levels. In survival analysis using Cox regression with parsimonious models, patients with baseline TC or LDL values > median, respectively, showed risks of 0.6(95% CI 0.4-0.9; p = 0.01) and 0.6(95%CI 0.4-0.9; p = 0.02) for malignancy onset, and 0.5(95% CI 0.3-0.8; p = 0.005) and 0.5(95% CI 0.3-0.8; p = 0.004) for neoplastic death. Similar results were obtained using competitive risk analysis with parsimonious models. CONCLUSIONS: This long-term prospective study of an unselected real-world patient sample showed that neoplasia onset and mortality are independently associated with low plasma TC and LDL levels at admission for ACS.

Trajectories of Blood Lipid Concentrations Over the Adult Life Course and Risk of Cardiovascular Disease and All-Cause Mortality: Observations From the Framingham Study Over 35 Years.

Background Elevated total cholesterol ( TC ), low-density lipoprotein cholesterol ( LDL -C), triglycerides, and non-high-density lipoprotein cholesterol (non- HDL -C) and low high-density lipoprotein cholesterol ( HDL -C) concentrations correlate with atherosclerotic cardiovascular disease ( ASCVD ) and mortality. Therefore, understanding how lipid trajectories throughout adulthood impact ASCVD and mortality risk is essential. Methods and Results We investigated 3875 Framingham Offspring participants (54% women, mean age 48 years) attending ≥1 examination between 1979 and 2014. We evaluated longitudinal correlates of each lipid subtype using mixed-effects models. Next, we clustered individuals into trajectories through group-based modeling. Thereafter, we assessed the prospective association of lipid trajectories with ASCVD and mortality. Male sex, greater body mass index, and smoking correlated with higher TC , LDL -C, triglycerides, non- HDL -C, and lower HDL -C concentrations. We identified 5 TC , HDL -C, and LDL -C trajectories, and 4 triglycerides and non- HDL -C trajectories. Upon follow-up (median 8.2 years; 199 ASCVD events; 256 deaths), elevated TC (>240 mg/ dL ), LDL -C (>155 mg/ dL ), or non- HDL -C (>180 mg/ dL ) concentrations conferred >2.25-fold ASCVD and mortality risk compared with concentrations <165 mg/ dL , <90 mg/ dL , and <115 mg/ dL , respectively ([ TC hazard ratio ( HR )ASCVD=4.17, 95% CI 1.94-8.99; TC HR death=2.47, 95% CI 1.28-4.76] [ LDL -C HRASCVD=5.09, 95% CI 1.54-16.85; LDL -C HR death=4.04, 95% CI 1.84-8.89] [non- HDL -C HRASCVD=4.60, 95% CI 1.98-10.70; LDL -C HR death=3.74, 95% CI 2.03-6.88]). Consistent HDL -C concentrations <40 mg/ dL were associated with greater ASCVD and mortality risk than concentrations >70 mg/ dL (HRASCVD=3.81, 95% CI 2.04-7.15; HR death=2.88, 95% CI 1.70-4.89). Triglycerides trajectories were unassociated with outcomes. Conclusions Using a longitudinal modeling technique, we demonstrated that unfavorable lipid trajectories over 35 years confer higher ASCVD and mortality risk later in life.

Combining cholesterol-lowering strategies with imaging data: a visible benefit?

Coronary artery disease is characterised by the development of atherosclerotic plaques and is associated with significant morbidity and mortality on a global level. However, many patients with atherosclerosis are asymptomatic and the prediction of acute coronary events is challenging. The role of imaging studies in characterising plaque morphology and stability is emerging as a valuable prognostic tool, while providing evidence for the beneficial effects of cholesterol-lowering therapy on plaque burden. This review provides an overview of contemporary studies describing the value of imaging strategies for atherosclerotic plaques. Coronary angiography is commonly used in the clinical setting, but requires a significant radiation dose (similar to computed tomography). Magnetic resonance imaging evaluation of coronary vessels would avoid exposure to ionising radiation, but is not yet feasible due to motion artefacts. The roles of alternative imaging techniques, including grey-scale intravascular ultrasound, optical coherence tomography and near-infrared spectroscopy have emerged in recent years. In particular, grey-scale intravascular ultrasound has been effectively applied to detect changes in plaque burden and features of plaques predictive of rupture, as well as plaque characteristics during cholesterol-lowering therapy, providing novel insights into factors that may contribute to treatment effectiveness. Challenges and limitations to the use of imaging techniques are considered in this context, along with future imaging strategies.

Statins and Elderly: From Clinical Trials to Daily Practice.

Elderly patients represent a rising social problem, due to the exponential growth of persons in these age groups and their atherothrombotic burden. The management of this population still raises several challenges, requiring a balance between elevated cardiovascular risk, clinical complexity, frailty and co-morbidities. Statins represent the main pillar in cardiovascular prevention, lowering serum cholesterol and reducing mortality and ischemic events, especially in high-risk patients. Yet, elderly patients have often been excluded from major clinical trials of statins, thus limiting the experience with these drugs in advanced age. Moreover, important barriers to the use of statins in the elderly exist due to potential risks attributed to altered metabolism, comorbidities, polypharmacy and drug-drug interactions and financial constraints. This situation has led to a "statin paradox", since high-risk elderly patients, that would most benefit from the use of statins, may be undertreated with these drugs in real life. The vague indications provided by guidelines mean that this issue is still debated, especially regarding primary prevention. Nevertheless, the benefits in outcome offered by statins cannot be neglected. Efforts should be made in order to focus on the importance of statin use in the elderly and to provide clinicians with adequate tools for case by case decisions.

Associations between risk of overall mortality, cause-specific mortality and level of inflammatory factors with extremely low and high high-density lipoprotein cholesterol levels among American adults.

BACKGROUND: The health outcomes associated with extremely low or high plasma concentrations of high-density lipoprotein cholesterol (HDL-C) are not well documented mainly because of the small numbers of participants with such values included in the clinical trials. OBJECTIVE: We prospectively investigated the association between extremely low and high HDL-C with: 1) the risk of overall, coronary heart disease (CHD), cerebrovascular and cancer mortality, and, 2) their link with inflammatory factors. METHODS: Analysis was based on subjects ≥18 years old from the National Health and Nutrition Examination Surveys (NHANES). We categorized HDL-C levels as follows: [low HDL-C group ≤30 (extremely low), 30-40 (low), and ≥40 (reference)] [high HDL-C group = 40-80 (reference), 80-100 (high) and ≥100 mg/dl (extremely high). Cox proportional hazard regression models and analysis of covariance accounted for survey design, masked variance and sample weights. RESULTS: After adjustment for age, race and sex, we found that the very low HDL-C category (<30 mg/dl) had a greater risk of total mortality (risk ratio [RR]: 3.00, 95%CI: 2.20-4.09). RR for CHD and stroke mortality was 2.00 and 2.53, respectively; there was no link between cancer and level of HDL-C (p = 0.235). The association between total mortality, CHD and stroke with the level of HDL-C attenuated but remained significant even after adjustment for demographics, dietary, cardiovascular risk factors and treatment for dyslipidemia (all p < 0.001). After adjustments, subjects with extremely high HDL-C levels had a higher risk of mortalities (all p < 0.001). Mexican-American ethnicity, subjects in the low level of HDL-C (30-40 mg/dl) category had higher risk of mortalities than those with a very low level (all p < 0.001). Concentration of C-reactive protein, fibrinogen and white blood count significantly decreased as the level of the HDL-C increased; these findings were robust after adjustment for demographics, dietary, cardiovascular risk factors and treatment for dyslipidemia (all p < 0.001); further subjects with extremely high HDL-C levels have a greater levels of inflammatory factors (all p < 0.001). CONCLUSIONS: Both extremely low and high HDL-C levels were associated with greater risk of mortalities (total, CHD and stroke) and higher level of inflammatory factors, while there was no link between level of HDL-C and risk of cancer. Moreover, we found evidence of an HDL-C paradox in Mexican-American ethnicity participants.

Attainment of lipid goals and long-term mortality after coronary-artery bypass surgery.

INTRODUCTION: There is paucity of data regarding lipid goal attainment after coronary-artery bypass graft surgery (CABG) and its impact on adverse outcomes. We aimed to investigate the attainment of lipid goals and the association between plasma lipid levels achieved after CABG and mortality. METHODS: Retrospective analysis of 1230 patients undergoing CABG. Mortality was examined in relation to most-recent lipid levels attained, categorized by clinically-relevant thresholds, and according to the improvement from pre-operative levels. RESULTS: Low-density lipoprotein cholesterol (LDL-C) < 70 mg/dL was attained by 44% of the patients. After multivariable adjustment, the hazard ratio for long-term mortality was 1.33 (95% confidence interval, 1.05-1.67) and 1.97 (1.55-2.50) for patients attaining LDL-C 70-100 mg/dL and >100 mg/dL, respectively, compared with LDL-C < 70 mg/dL. The hazard ratio was 1.42 (1.07-1.88) and 1.73 (1.33-2.23) for patients attaining high-density lipoprotein cholesterol (HDL-C) 40-50 mg/dL and <40 mg/dL, respectively, compared with HDL-C > 50 mg/dL; and 1.11 (0.85-1.45) and 4.28 (1.89-9.68) for patients with triglycerides 200-500 mg/dL and >500 mg/dL compared with triglycerides <200 mg/dL. A progressive stepwise association was seen between the cumulative status of the lipid measures achieved and long-term mortality, with the lowest risk observed in those with optimal level of all lipid measures ( p < 0.0001). Improvement in any of the lipid measures from pre-operative to latest documented levels was associated with reduced mortality. CONCLUSIONS: Lack of attainment of optimal levels of routine lipid measures after CABG was common and associated both independently and additively with long-term mortality, emphasizing the importance of addressing plasma lipid profile as both a risk marker and a treatment target after CABG.