Lipid Lowering Drugs in Acute Coronary Syndromes (ACS).

PURPOSE OF REVIEW: The purpose of this review is to critically discuss whether more aggressive lipid-lowering strategies are needed in patients with acute coronary syndromes (ACS). RECENT FINDINGS: Currently, available data on early (in-hospital/discharge) administration of potent lipid-lowering drugs, such as proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitors in patients during the vulnerable post-ACS phase, have clearly demonstrated clinical efficacy of the "strike early and strike strong" approach not only for rapid reduction of low-density lipoprotein cholesterol (LDL-C) to unprecedentedly low levels, but also for associated favorable composition of coronary plaque. Intensive lipid-lowering therapy with rapid achievement of the LDL-C treatment goal in ACS patients seems reasonable. However, whether such profound LDL-C reduction would result in additional benefit on the reduction of future CV events still has to be established. Thus, data addressing CV outcomes in such vulnerable patients at extreme CV risk are urgently needed.

Prevalence and factors associated with lipid-lowering medications use for primary and secondary prevention of cardiovascular diseases among Malaysians: the REDISCOVER study.

BACKGROUND: Lipid-lowering medications (LLM) are commonly used for secondary prevention, as well as for primary prevention among patients with high global cardiovascular risk and with diabetes. This study aimed to determine the prevalence of LLM use among high-risk individuals [participants with diabetes, high Framingham general cardiovascular (FRS-CVD) score, existing cardiovascular disease (CVD)] and the factors associated with it. METHODS: This is a cross-sectional analysis from the baseline recruitment (years 2007 to 2011) of an ongoing prospective study involving 11,288 participants from 40 rural and urban communities in Malaysia. Multiple logistic regression was used to identify characteristics associated with LLM use. RESULTS: Majority (74.2%) of participants with CVD were not on LLM. Only 10.5% of participants with high FRS-CVD score, and 17.1% with diabetes were on LLM. Participants who were obese (OR = 1.80, 95% CI: 1.15-2.83), have diabetes (OR = 2.38, 95% CI: 1.78-3.19), have hypertension (OR = 2.87, 95% CI: 2.09-3.95), and attained tertiary education (OR = 2.25, 95% CI: 1.06-4.78) were more likely to be on LLM. Rural residents had lower odds of being on LLM (OR = 0.58, 95% CI: 0.41-0.82). In the primary prevention group, participants with high FRS-CVD score (OR = 3.81, 95% CI: 2.78-5.23) and high-income earners (OR = 1.54, 95% CI: 1.06-2.24) had higher odds of being on LLM. CONCLUSIONS: LLM use among high CVD-risk individuals in the primary prevention group, and also among individuals with existing CVD was low. While CVD risk factors and global cardiovascular risk score were positively associated with LLM use, sociodemographic disparities were observed among the less-educated, rural residents and low-income earners. Measures are needed to ensure optimal and equitable use of LLM.

Lipid-lowering medication use and cancer-specific survival among endometrial or lung cancer patients: an Australian nationwide cohort study.

PURPOSE: Inconsistent results of lipid-lowering medications (LLMs) on improved cancer survival need more investigations. We tested the hypothesis that adherence to the drug would be associated with a lower cancer-specific mortality in a homogeneous population who has ever used the drug. METHODS: Utilising data from the Australian Cancer database, linked to the Pharmaceutical Benefits Scheme data and the National Death Index, we identified two separate cohorts of 4519 and 3083 women patients with newly diagnosed endometrial and lung cancer respectively between 2003 and 2013. Adherence to this drug was calculated by proportion of days covered. Cox regression models with time-varying covariates were used to estimate the multivariable-adjusted cause-specific hazard ratios (HRs) and 95% confidence intervals (CIs) for the association of adherence to LLMs, statins, lipophilic and hydrophilic statins, and cancer-specific mortality. RESULTS: Each 10% increase in 1-year adherence to LLMs reduced cancer-specific mortality among women with endometrial cancer (adjusted HR=0.93, 95% CI 0.90-0.96) or lung cancer (adjusted HR=0.95, 95% CI 0.93-0.97). The inverse associations remained unchanged in different subgroup analyses. The reductions in lung cancer mortality were not apparent for women who adhered to lipophilic statins albeit better endometrial cancer survival appeared in the lipophilic statin group and borderline statistical improvement in the hydrophilic statin group. CONCLUSIONS: Among LLM users, adherence to this drug is inversely associated with reduced cancer-specific mortality. Together with previous evidence, randomised controlled trials are called for to confirm whether LLMs could be considered as an adjuvant treatment to improve prognosis.

Modifiable Factors Associated with Non-adherence to Antihypertensive or Antihyperlipidemic Drugs Are Dissimilar: a Multicenter Study Among Patients with Diabetes in Indonesia.

BACKGROUND: To develop targeted and tailored interventions for addressing medication non-adherence, it is important to identify underlying factors. OBJECTIVE: To identify factors associated with non-adherence as well as subtypes of non-adherence to antihypertensive or antihyperlipidemic drugs among patients with type 2 diabetes in Indonesia. DESIGN: An observational multicenter cross-sectional survey. PARTICIPANTS: Patients with type 2 diabetes using either antihypertensive or antihyperlipidemic drugs in four regions in Indonesia. MAIN MEASURES: Non-adherence and its subtypes of intentional and unintentional non-adherence were assessed using the Medication Adherence Report Scale. Necessity and concern beliefs were assessed with the Beliefs about Medicines Questionnaire. We applied binary and multinomial logistic regression to assess associations of medication beliefs, sociodemographic factors, and clinical-related factors to non-adherence and report odds ratios (OR) with 95% confidence intervals (CI). KEY RESULTS: Of 571 participating patients (response rate 97%), 45.5% and 52.7% were non-adherent to antihypertensive and antihyperlipidemic drugs, respectively. Older age was associated with non-adherence to antihypertensive drugs (60-69 years) (OR, 5.65; 95% CI, 2.68-11.92), while higher necessity beliefs (OR, 0.92; 95% CI, 0.88-0.95) were associated with less non-adherence. Factors associated with non-adherence to antihyperlipidemic drugs were female gender (OR, 1.84; 95% CI, 1.03-3.27) and higher concern beliefs (OR, 1.10; 95% CI, 1.03-1.18), while higher necessity beliefs (OR, 0.89; 95% CI, 0.83-0.96) were associated with less non-adherence. CONCLUSIONS: The main factors associated with non-adherence to antihypertensive and antihyperlipidemic drugs are modifiable. In general, beliefs about the necessity of the drug are important but for antihyperlipidemic drugs concerns are important as well. Healthcare providers should pay attention to identify and address medication beliefs during patient counselling.

Lifetime risk assessment in cholesterol management among hypertensive patients: observational cross-sectional study based on electronic health record data.

BACKGROUND: In hypertensive patients, reducing plasma low-density lipoprotein cholesterol level (LDL-C) is one of the main interventions for preventing chronic cardiovascular diseases (CVD). However, LDL-C control remains generally insufficient, also in patients with hypertension. We analyzed Electronic Health Record (EHR) data of 7117 hypertensive patients to find the most potential age and sex subgroups in greatest need for improvement in real life dyslipidemia treatment. Taking into account the current discussion on lifetime CVD risk, we focused on the age dependence in LDL-C control. METHODS: In this observational cross-sectional study, based on routine electronic health record (EHR) data, we investigated LDL-C control of hypertensive, non-diabetic patients without renal dysfunction or CVD, aged 30 years or more in Finnish primary care setting. RESULTS: More than half (54% of women and 53% of men) of untreated patients did not meet the LDL-C target of < 3 mmol/l and one third (35% of women and 33% of men) of patients did not reach the target even with the lipid-lowering medication (LLM). Furthermore, higher age was strongly associated with better LDL-C control (p < 0.001) and lower LDL-C level (p < 0.001) in individuals with and without LLM. Higher age was also strongly associated with LLM prescription (p < 0.001). In total, about half of the patients were on LLM (53% of women and 51% of men). CONCLUSIONS: Our findings indicate that dyslipidemia treatment among Finnish primary care hypertensive patients is generally insufficient, particularly in younger age groups who might benefit the most from CVD risk reduction over time. Clinicians should probably rely more on the lifetime risk of CVD, especially when treating working age hypertensive patients.

Statins as a free pass: Body mass index and other cardiovascular risk factors among lipid-lowering medication users and nonusers in the California Men's Health Study.

To lower risk from cardiovascular disease (CVD), national guidelines recommend lifestyle changes followed by use of lipid-lowering medications when appropriate. Previous studies have questioned whether individuals taking these medications are less likely to modify their dietary intake and physical activity, resulting in increased body mass index (BMI). We assessed BMI and CVD clinical risk factors over time between lipid-lowering medication users and nonusers in a diverse cohort of middle-aged and older men. The cohort consisted of 63,357 men who enrolled in the California Men's Health Study between 2002 and 2003 and were not taking lipid-lowering medications at baseline. Lipid-lowering medication use was determined over twelve years of follow-up. BMI and other CVD risk factors were assessed with longitudinal linear mixed effect models adjusting for possible confounders. Overall, lipid-lowering medication users had higher BMI than nonusers (p < .0001); however, there was a decrease over time for both groups (p < .0001). Total cholesterol, LDL-C, and triglycerides decreased for users and nonusers (p < .0001). While HDL-C was higher for nonusers (p < .05), over time this measure increased in both groups (p < .0001). We found no evidence of increases in BMI after initiation of lipid-lowering medication in this cohort. Instead, BMI decreased and several cholesterol-related CVD risk factors improved for lipid-lowering medication users and nonusers. This suggests that men placed on lipid-lowering medications do not view them as a panacea for their increased risk of cardiovascular disease. Instead, they appear to perceive them as one component of a multi-pronged strategy including lifestyle and nutrition as suggested by current guidelines.

Muscle Mass and Body Fat in Relation to Cardiovascular Risk Estimation and Lipid-Lowering Eligibility.

This cross-sectional population-based study aimed to evaluate the relationships of muscle-mass and body-fat phenotypes to 10-yr risk of cardiovascular disease (CVD) events and eligibility for lipid management. Participants were Korean adults (N = 7315; 3163 men, 4152 women) aged 40-79 yr, free from stroke and coronary heart disease, who provided complete data for estimating 10-yr CVD risk and body composition during the Fifth Korea National Health and Nutrition Examination Survey (2009-2010). Four levels of combined muscle mass and body fat were determined using sex-specific quintiles of appendicular skeletal muscle mass divided by height squared, and sex-specific quintiles of total body fat percentage. Ten-year CVD risk was calculated using Pooled Cohort Equations and Framingham risk scores. Lipid-lowering medication eligibility was determined using American College of Cardiology/American Heart Association (ACC/AHA) and Adult Treatment Panel (ATP) III guidelines. Compared with the reference group, the risk of CVD events was higher in men with low muscle mass, high body fat, or the 2 factors combined. CVD risk was lower in women with low muscle mass, higher in women with high body fat, and nonsignificant in women with the 2 factors. Participants with low muscle mass and high body fat had higher odds for medication eligibility using the ACC/AHA guidelines but not the ATP III guidelines. Higher estimated 10-yr CVD risk was associated with combined phenotypes of low muscle mass and high fat in men but not in women. Also, the relationship of these phenotypes to lipid-lowering medication eligibility was guideline-specific.

A systematic review of interventions to improve adherence to statin medication: What do we know about what works?

Suboptimal adherence to statin medication is common and leads to serious negative health consequences but may respond to intervention. This review evaluated the effectiveness of interventions intended to improve adherence to statin medication. Data sources included peer-reviewed publications from Cochrane Register of Randomized Controlled Trials (RCTs), PubMed, CINAHL, and EMBase indexed between 01 October 2008 and 18 October 2015 and studies from reference lists and technical experts. RCTs that evaluated an intervention targeting adherence to self-administered statin medication for primary or secondary prevention were eligible. Two investigators independently reviewed trials, extracted data, and evaluated risk of bias. Twenty-nine RCTs reporting on 39,769 patients met inclusion. Identified RCTs exhibited methodological weaknesses: all but one failed to set inclusion parameters for medication adherence; nearly half lacked sufficient power to detect meaningful effects; and the majority had a risk of bias. Interventions were categorized into five classes (simplification of regimen, prescription cost coverage, reminders, education and information, and multi-faceted) and effects were pooled within each class. Prescription cost coverage, Hedges' g=0.15, 95%CI [0.11:0.21], simplification of drug regimen, Hedges' g=0.38, 95%CI [0.22:0.55], the provision of education, Hedges' g=0.19, 95%CI [0.01:0.37], and the use of multi-faceted interventions, Hedges' g=0.16, 95%CI [0.05:0.27], had small positive effects on statin adherence relative to usual care and reminders were promising, Hedges' g=0.0.27, 95%CI [-0.05:0.60]. In conclusion, there are some successful interventions to improve adherence to statin medication but the effects are small and additional methodologically rigorous trials are needed.

Sociodemographic and diagnostic characteristics of prescribing a second-line lipid-lowering medication: ezetimibe used as initial medication, switch from statins, or add-on medication.

OBJECTIVE: Ezetimibe is used as a second-line lipid-lowering medication (LLM) if statin therapy is not tolerated or cholesterol targets are not reached by statins alone. We aimed to investigate the impact of sociodemographic factors on ezetimibe initiation as (a) incident LLM therapy, (b) add-on therapy, and (c) switch from statins. METHODS: All individuals aged 30+ who had filled at least one prescription for either statins (N = 581.074) or ezetimibe (N = 7.932) in 2011 were followed in the nationwide Danish registries to explore LLM prescribing patterns from 1 January 2011 to end 2012. Using logistic regression analyses, the odds ratio (OR) with 95% confidence intervals (CIs) was calculated for (a) incident ezetimibe use among LLM initiators (N = 77,472), (b) ezetimibe switching by discontinuing statin users (N = 37,509), and (c) ezetimibe as add-on by non-discontinuing statin users (N = 442,672). RESULTS: Women had higher odds for initiating ezetimibe than men (switch OR = 1.55; 95% CI = 1.32-1.82). While prior use of newer high-potency statins was the strongest predictor (add-on (5.56; 4.95-6.24), income was the strongest socioeconomic predictor for incident LLM use (1.33; 1.14-1.56) and switching (1.64; 1.27-2.13). Both income and education were predictors for add-on therapy, with the educational effect mediated by prior use of high-potency statins. Odds for ezetimibe prescribing were highest in myocardial infarction patients. CONCLUSION: While higher income is a predictor for switching to ezetimibe, both higher education and income are weak predictors for using ezetimibe as add-on therapy. Women and individuals with myocardial infarction are more likely to be prescribed ezetimibe than others, despite lack of evidence of ezetimibe lowering the risk of cardiovascular events.

Five year trends in dyslipidaemia prevalence and management in Switzerland: the CoLaus study.

BACKGROUND AND AIMS: Data from prospective cohorts describing dyslipidaemia prevalence and treatment trends are lacking. Using data from the prospective CoLaus study, we aimed to examine changes in serum lipid levels, dyslipidaemia prevalence and management in a population-based sample of Swiss adults. METHODS AND RESULTS: Cardiovascular risk was assessed using PROCAM. Dyslipidaemia and low-density lipoprotein cholesterol (LDL-C) target levels were defined according to the Swiss Group for Lipids and Atherosclerosis. Complete baseline and follow up (FU) data were available for n = 4863 subjects during mean FU time of 5.6 years. Overall, 32.1% of participants were dyslipidaemic at baseline vs 46.3% at FU (p < 0.001). During this time, lipid lowering medication (LLM) rates among dyslipidaemic subjects increased from 34.0% to 39.2% (p < 0.001). In secondary prevention, LLM rates were 42.7% at baseline and 53.2% at FU (p = 0.004). In multivariate analysis, LLM use among dyslipidaemic subjects, between baseline and FU, was positively associated with personal history of CVD, older age, hypertension, higher BMI and diabetes, while negatively associated with higher educational level. Among treated subjects, LDL-C target achievement was positively associated with diabetes and negatively associated with personal history of CVD and higher BMI. Among subjects treated at baseline, LLM discontinuation was negatively associated with older age, male sex, smoking, hypertension and parental history of CVD. CONCLUSIONS: In Switzerland, the increase over time in dyslipidaemia prevalence was not paralleled by a similar increase in LLM. In a real-life setting, dyslipidaemia management remains far from optimal, both in primary and secondary prevention.

Persistence and Adherence to PCSK9 Inhibitor Monoclonal Antibodies Versus Ezetimibe in Real-World Settings.

INTRODUCTION: The cardiovascular disease risk reduction benefits of proprotein convertase subtilisin/kexin type 9 inhibitor monoclonal antibodies (PCSK9i mAb) and ezetimibe are dependent on remaining on treatment and being persistent and adherent. We estimated the percentage of patients on therapy, persistent and adherent at 182 and 365 days among US adults with health insurance who initiated a PCSK9i mAb (n = 16,588) or ezetimibe (n = 83,086) between July 2015 and December 2019. METHODS: Using pharmacy fill claims, being on therapy was defined as having a day of medication supply in the last 60 of 182 and 365 days following treatment initiation, being persistent was defined as not having a gap of 60 days or more between the last day of supply from one prescription fill and the next fill, and being adherent was defined by having medication available to take on ≥ 80% of the 182 and 365 days following treatment initiation. We estimated multivariable-adjusted risk ratios for being persistent and adherent comparing patients initiating PCSK9i mAb versus ezetimibe using Poisson regression. RESULTS: At 182 days following initiation, 80% and 68% were on therapy and 76% and 64% were persistent among patients who initiated a PCSK9i mAb and ezetimibe, respectively. Among patients who were on therapy and persistent at 182 days following initiation, 88% and 81% of those who initiated a PCSK9i mAb and ezetimibe, respectively, were on therapy at 365 days. Among those on therapy and persistent at 182 days following initiation, being persistent and being adherent at 365 days were each more common among PCSK9i mAb versus ezetimibe initiators (persistent: 82% versus 76%, multivariable-adjusted risk ratio 1.07; 95% confidence interval [CI] 1.06-1.08; adherent: 74% versus 71%, multivariable-adjusted risk ratio 1.02; 95% CI 1.01-1.03). CONCLUSIONS: These data suggest approaches to increase persistence and adherence to PCSK9i mAb and ezetimibe should be implemented prior to or within 182 days following treatment initiation.

Lipid-Lowering Medication and Outcomes After Anatomical and Functional Imaging in Suspected Coronary Artery Disease.

BACKGROUND: Anatomical and functional imaging identify different phenotypes of coronary artery disease (CAD) that may have implications for lipid-lowering medication (LLM). OBJECTIVES: The aim of this study was to assess the associations between LLM and long-term outcomes after combined anatomical and functional imaging in patients with suspected obstructive CAD. METHODS: Consecutive patients (n = 1,973; 41% men; median age: 63 years) underwent coronary computed tomography angiography (CTA) because of suspected CAD. Patients in whom obstructive CAD was not ruled out by CTA underwent ischemia testing by positron emission tomography. Data on LLM purchases were collected until 2 years, and the combined endpoints of death, myocardial infarction, and unstable angina pectoris were assessed at a median of 6.7 years. RESULTS: After imaging, LLM was used by 24% of patients with no CAD, 51% of patients with nonobstructive CAD, 72% of patients with obstructive CAD on CTA without myocardial ischemia, and 91% of patients with myocardial ischemia. The use of LLM decreased during follow-up, with 77% of patients with myocardial ischemia using LLM for 2 years. The use of LLM was associated with a lower annual rate of adverse events in patients with myocardial ischemia (6.1% vs 2.8%; P = 0.032) or obstructive CAD without myocardial ischemia (2.9% vs 1.4%; P = 0.004) but not in patients with nonobstructive CAD (1.5% vs 1.4%; P = 0.89) or no CAD (0.3% vs 0.3%; P = 0.68). CONCLUSIONS: The CAD phenotype defined by anatomical and functional imaging guides the use of LLM. The presence of myocardial ischemia and anatomical obstructive coronary lesions were associated with a long-term outcome benefit from LLM.

Are Lipid-Lowering and Antihypertensive Medications Used as Complements to Heart-Healthy Diets? A Scoping Review.

In cardiovascular disease (CVD) prevention, whether antihypertensive and lipid-lowering medications are used as complements to heart-healthy diets has not been thoroughly assessed. This scoping review aimed to 1) analyze observational studies that assessed the relationship between diet and antihypertensive/lipid-lowering medication use and 2) evaluate whether medication was used as a complement to heart-healthy dietary intakes. We searched MEDLINE, Embase, Web of Science, and CINAHL through 14 January, 2023, for studies that assessed either 1) intraindividual changes in diet associated with lipid-lowering/antihypertensive medication initiation or use or 2) interindividual differences in diet between users and nonusers of these medications. A total of 17 studies were included. Of those, 3 prospectively assessed the intraindividual changes in diet associated with medication initiation or use, but none documented potential changes in diet prior to medication initiation. The 14 other studies compared dietary intakes of medication users and nonusers, most of which also relied on an incomplete assessment of the temporal dynamics between diet and medication use as they employed cross-sectional (n = 12) or repeated cross-sectional (n = 2) designs. Data from 8 studies, including 4 of the 5 studies from Europe, suggested that medication was used as a complement to heart-healthy diets, whereas data from the 9 other studies, including the 4 conducted in the United States, provided no such evidence, indicating potential between-country differences in this relationship. Finally, no studies investigated how the dynamics between diet and medication use influenced the long-term CVD risk. This scoping review suggests that the current literature on the relationship between lipid-lowering/antihypertensive medication use and diet provides an incomplete perspective on how medication may influence diet in CVD prevention. Prospective studies assessing intraindividual changes in diet associated with medication initiation and use and how these dynamics influence the CVD risk are thus needed.

Optimization of the MACE endpoint composition to increase power in studies of lipid-lowering therapies-a model-based meta-analysis.

Aims: To develop a model-informed methodology for the optimization of the Major Adverse Cardiac Events (MACE) composite endpoint, based on a model-based meta-analysis across anti-hypercholesterolemia trials of statin and anti-PCSK9 drugs. Methods and results: Mixed-effects meta-regression modeling of stand-alone MACE outcomes was performed, with therapy type, population demographics, baseline and change over time in lipid biomarkers as predictors. Randomized clinical trials up to June 28, 2022, of either statins or anti-PCSK9 therapies were identified through a systematic review process in PubMed and ClinicalTrials.gov databases. In total, 54 studies (270,471 patients) were collected, reporting 15 different single cardiovascular events. Treatment-mediated decrease in low density lipoprotein cholesterol, baseline levels of remnant and high-density lipoprotein cholesterol as well as non-lipid population characteristics and type of therapy were identified as significant covariates for 10 of the 15 outcomes. The required sample size per composite 3- and 4-point MACE endpoint was calculated based on the estimated treatment effects in a population and frequencies of the incorporated events in the control group, trial duration, and uncertainty in model parameters. Conclusion: A quantitative tool was developed and used to benchmark different compositions of 3- and 4-point MACE for statins and anti-PCSK9 therapies, based on the minimum population size required to achieve statistical significance in relative risk reduction, following meta-regression modeling of the single MACE components. The approach we developed may be applied towards the optimization of the design of future trials in dyslipidemia disorders as well as in other therapeutic areas.

Impact of conducting a genetic study on the management of familial hypercholesterolemia.

BACKGROUND: Clinically diagnosed familial hypercholesterolemia (FH) may require a genetic test (GT) to confirm diagnosis. GT availability/accessibility is resource-dependent and usually restricted to specialized clinics. While GT has a diagnostic value, it has not yet defined its impact on long-term management and prognosis of FH. OBJECTIVE: The aim was to identify the clinical characteristics associated with the request for a GT in suspected heterozygous FH. METHODS: Retrospective study including adult patients with clinically suspected to be FH. Positive GT (GT+) was defined as having a pathogenic/likely pathogenic variant. Patients were stratified based on whether they had a genetic study conducted, and among those with a genetic study, according to those who did or did not have a GT+. RESULTS: From 4854 patients included, 3090 were performed a GT (GT+: 2113). Median follow-up: 6.2 years. A younger age, FH-related physical signs, premature coronary disease, higher low-density lipoprotein cholesterol (LDLc) and lower body mass index and triglycerides, associated higher odds of being conducted a genetic study. These patients had higher baseline LDLc (252 mg/dL vs. 211 mg/dL among clinically diagnosed patients) and experienced larger reductions over the follow-up (157.7 mg/dL vs. 113.5 mg/dL, respectively). A similar pattern was observed among patients with GT+ (vs. negative GT). LDLc target attainment was low but increased to 66-95% when a triple combination with statin/ezetimibe/proprotein convertase subtilisin kexin type 9-inhibitor was used. Cardiovascular events occurred in 3.2% and 3.1% of patients who conducted/not conducted a genetic study. Patients conducted a genetic analysis and those with GT+ tended to present the events earlier. CONCLUSIONS: Genetic study, vs. having a clinical-only diagnosis, impacts the management of FH. Cardiovascular prognosis was similar in both groups, perhaps as a result of the more intensive management of patients with a genetic study.

Reduction of cardiovascular events with the use of lipid-lowering medication in patients with familial hypercholesterolemia or severe primary hypercholesterolemia: A systematic review.

BACKGROUND: Lipid-lowering medication is effective in reducing the risk of cardiovascular disease in several clinical scenarios. However, the evidence in patients with familial hypercholesterolemia (FH) and severe primary hypercholesterolemia is less robust. OBJECTIVES: The main objective of the present systematic review was to analyze the association between lipid-lowering medication and cardiovascular risk reduction in patients with FH or severe primary hypercholesterolemia. METHODS: This systematic review was performed according to PRISMA guidelines. A literature search was performed to detect studies that evaluated the association between lipid-lowering medication and cardiovascular events in FH patients. The diagnosis of FH varied in the studies analyzed. Genetic and clinical criteria or a combination of both were used. Likewise, we considered patients with severe primary hypercholesterolemia. RESULTS: Fourteen studies including 21059 patients were considered eligible for this research. This systematic review showed that the vast majority of the studies with statins reported a significant cardiovascular risk reduction. Statin use was associated with a lower risk of major adverse cardiovascular events (3 studies), coronary heart disease (2 studies), cardiovascular death (4 studies), all-cause mortality (4 studies) and combined endpoint of coronary heart disease and mortality (1 study). When analyzing the association between non-statin lipid-lowering medications and the incidence of cardiovascular events, the results were conflicting. CONCLUSION: Despite the low level of evidence, this systematic review showed that statins reduce cardiovascular events in patients with HeFH. Evidence for other lipid-lowering drugs is not conclusive.

Adherence to Statin Therapy and Attainment of LDL Cholesterol Targets in an Outpatient Population of Type 2 Diabetes Patients: Analysis in the DIAbetes and LifEstyle Cohort Twente (DIALECT).

Objective: To assess adherence to statin therapy and its association with sociodemographic data, medical characteristics, LDLc levels, and LDLc target attainment in real-world T2D patients treated in secondary care. Research Design and Methods: Cross-sectional analyses were performed on baseline data of 393 patients in the DIAbetes and LifEstyle Cohort Twente (DIALECT). The medication possession ratio (MPR), calculated with pharmacy dispensing data, was used to determine adherence to statins for an intended period of 24 months. Statins were included in the analyses if they were used for at least six consecutive months with at least three dispenses. Adherence was defined as an MPR ≥80%. Associations with adherence were assessed using descriptive statistics and binary logistic regression. Results: Overall, 80% of the patients had a statin prescription and of those, 89% were adherent. The proportion of patients who reached LDLc targets of ≤2.5 mmol/L and <1.8 mmol/L differed significantly between the adherent, nonadherent and non-statin group (90% vs. 74% vs. 46%; p < 0.01 and 56% vs. 26% vs. 6%; p < 0.01, respectively). Serum LDLc levels were lower in the adherent versus the nonadherent and non-statin group (1.76 ± 0.60 vs. 2.23 ± 0.90 vs. 2.71 ± 0.67 mmol/L; p < 0.01). Higher HbA1c levels were independently associated with nonadherence (OR: 1.05, 95% CI 1.01-1.08; p < 0.01). Mediation adherence (OR: 2.88, 95% CI 1.04-7.97; p = 0.041) and lower BMI (OR: 0.88, 95% CI 0.81-0.96; p < 0.01) were independently associated with attaining the LDLc target of ≤2.5 mmol/L. Conclusion: In patients with T2D treated in secondary care, statin adherence was relatively high and was associated with significantly lower LDLc levels. It is important to identify nonadherence as it appeared an important determinant of failure to reach LDLc targets. The finding that many patients who failed to attain LDLc targets did not receive statin treatment offers an opportunity to improve diabetes care.

Emotional Distress is Associated with Lower Health-Related Quality of Life Among Patients with Diabetes Using Antihypertensive and/or Antihyperlipidemic Medications: A Multicenter Study in Indonesia.

OBJECTIVE: To evaluate the associations between different types of diabetes distress and health-related quality of life (HRQOL) among patients with type 2 diabetes (T2DM) using antihypertensive and/or antihyperlipidemic medications in Indonesia and to explore the differences between those using only antihypertensive, only antihyperlipidemic, or both medications. METHODS: A multicenter cross-sectional study was conducted in Community Health Centers in three cities in Indonesia among patients with T2DM aged at least 18 years who were using antihypertensive and/or antihyperlipidemic medications. Diabetes distress subscales (emotional, regimen-related, interpersonal, and physician-related distress) and HRQOL were assessed using a validated diabetes distress scale-17 and EQ-5D-5L scale, respectively. Multiple linear regression models were used to evaluate the associations between different types of diabetes distress and HRQOL adjusting for confounders. RESULTS: Most of the 503 participants were females (67.6%) and aged 60-69 years (40.8%). Emotional distress was negatively associated with HRQOL among the whole group of patients (ß: -0.08; 95% confidence interval (CI): -0.10, -0.05; p < 0.001). This association was similar across all therapeutic subgroups. Regimen-related distress (ß: -0.06; 95% CI: -0.09, -0.03; p < 0.001) and interpersonal distress (ß: -0.02; 95% CI: -0.05, -0.01; p = 0.022) were negatively associated, whereas physician-related distress (ß: 0.04; 95% CI: 0.01, 0.07; p = 0.037) was positively associated with HRQOL among the whole group. These associations were also observed among those using only antihypertensive medication. CONCLUSION: Emotional distress affects HRQOL in T2DM patients treated for cardiovascular comorbidities, independent of antihypertensive and/or antihyperlipidemic medication use.

Endothelium as a Therapeutic Target in Diabetes Mellitus: From Basic Mechanisms to Clinical Practice.

Endothelium plays an essential role in human homeostasis by regulating arterial blood pressure, distributing nutrients and hormones as well as providing a smooth surface that modulates coagulation, fibrinolysis and inflammation. Endothelial dysfunction is present in Diabetes Mellitus (DM) and contributes to the development and progression of macrovascular disease, while it is also associated with most of the microvascular complications such as diabetic retinopathy, nephropathy and neuropathy. Hyperglycemia, insulin resistance, hyperinsulinemia and dyslipidemia are the main factors involved in the pathogenesis of endothelial dysfunction. Regarding antidiabetic medication, metformin, gliclazide, pioglitazone, exenatide and dapagliflozin exert a beneficial effect on Endothelial Function (EF); glimepiride and glibenclamide, dipeptidyl peptidase-4 inhibitors and liraglutide have a neutral effect, while studies examining the effect of insulin analogues, empagliflozin and canagliflozin on EF are limited. In terms of lipid-lowering medication, statins improve EF in subjects with DM, while data from short-term trials suggest that fenofibrate improves EF; ezetimibe also improves EF but further studies are required in people with DM. The effect of acetylsalicylic acid on EF is dose-dependent and lower doses improve EF while higher ones do not. Clopidogrel improves EF, but more studies in subjects with DM are required. Furthermore, angiotensin- converting-enzyme inhibitors /angiotensin II receptor blockers improve EF. Phosphodiesterase type 5 inhibitors improve EF locally in the corpus cavernosum. Finally, cilostazol exerts favorable effect on EF, nevertheless, more data in people with DM are required.

Lipoprotein Subfractions and Glucose Homeostasis in Prediabetes and Diabetes in Taiwan.

AIMS: Prediabetes and diabetes are associated with increased insulin resistance and decreased insulin production, dyslipidemia, and increased cardiovascular disease (CVD) risk. Our goals were to assess lipoprotein subfractions using novel assays in such subjects. METHODS: Fasting normal, prediabetic, and diabetic Taiwanese men and women (n=2,049) had their serum glucose, glycosylated hemoglobin, insulin, total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), HDL3-C, apolipoprotein E-HDL-C, direct low-density lipoprotein cholesterol (LDL-C), small dense LDL-C (sdLDL-C), LDL-TG, and remnant lipoprotein cholesterol (RLP-C) levels measured using novel assays. HDL2-C, LDL-C, and large-buoyant LDL-C (lbLDL-C) were calculated. RESULTS: Prediabetic male and female subjects had significantly higher levels of TG, RLP-C, sdLDL-C, the sdLDL-C/LDL-C ratio, and LDL-TG than normal subjects, and statin treatment abolished this effect in men, but not in women. Diabetic male and female subjects had significantly higher TG and sdLDL-C/LDL-C ratios, and significantly lower levels of HDL-C, HDL2-C, HDL3-C, and apoE HDL-C than normal subjects, as did prediabetic women. Median direct LDL-C levels were ＞100 mg/dL in all groups, even in those receiving statin therapy. Calculated LDL-C significantly underestimated direct LDL-C by ＞10% in diabetic subjects. CONCLUSIONS: Our data indicate that prediabetic subjects were more likely to have significantly elevated RLP-C, sdLDL-C, and LDL-TG, while diabetic subjects were more likely to have significantly decreased HDL-C, HDL2-C, HDL3-C, and apoE HDL-C than normal subjects, and calculated LDL-C significantly underestimated their direct LDL-C. In our view, direct LDL-C and sdLDL-C should be measured and optimized in both diabetic and prediabetic subjects to reduce CVD risk.