Sex-related differences in premature cardiovascular disease in familial hypercholesterolemia

BACKGROUND: Familial hypercholesterolemia (FH) is associated with an increased prevalence of premature atherosclerotic cardiovascular disease (ASCVD), however, little is known about sex-specific differences in premature ASCVD and its risk factors. OBJECTIVE: The present study seeks to assess the burden and risk factors for premature ASCVD among men and women with FH. METHODS: In this study we retrospectively examined sex-specific differences in ASCVD prevalence, risk factor burdens, and lipid treatment outcomes in 782 individuals with clinically or genetically confirmed FH treated in 5 U.S. lipid and genetics clinics. A generalized linear model using Binomial distribution with random study site effect and sex-stratified analysis was used to determine the strongest predictors of premature ASCVD, and lipid treatment outcomes. Covariates included age, sex, diabetes mellitus (DM), hypertension, and current smoking. RESULTS: Among the cohort, 98/280 men (35%) and 89/502 women (18%) had premature ASCVD (defined as \u3c55 years in men and \u3c65 years in women). Women with premature ASCVD had higher mean treated total cholesterol (216 vs. 179 mg/dl, p=\u3c0.001) and LDL-C (135 vs. 109 mg/dl, p= 0.005). CONCLUSION: These data confirm that high percentages of women and men with FH develop premature ASCVD, and suggest that FH may narrow the observed sex difference in premature ASCVD onset. These data support more aggressive prevention and treatment strategies in FH, including in women, to reduce non-lipid risk factors and residual hypercholesterolemia

Racial disparities in modifiable risk factors and statin usage in Black patients with familial hypercholesterolemia

Background Black men and women are at higher risk for, and suffer greater morbidity and mortality from, atherosclerotic cardiovascular disease (ASCVD) compared with adults of European Ancestry (EA). Black patients with familial hypercholesterolemia are at particularly high risk for ASCVD complications because of lifelong exposure to elevated levels of low-density-lipoprotein cholesterol. Methods and Results This retrospective study analyzed ASCVD prevalence and risk factors in 808 adults with heterozygous familial hypercholesterolemia from 5 US-based lipid clinics, and compared findings in Black versus EA patients. Multivariate logistic regression models were used to determine the strongest predictors of ASCVD as a function of race. No significant difference was noted in the prevalence of ASCVD in Black versus EA patients with familial hypercholesterolemia (39% versus 32%, respectively

Effect of health information technology interventions on lipid management in clinical practice: A systematic review of randomized controlled trials

BACKGROUND: Large gaps in lipid treatment and medication adherence persist in high-risk outpatients in the United States. Health information technology (HIT) is being applied to close quality gaps in chronic illness care, but its utility for lipid management has not been widely studied. OBJECTIVE: To perform a qualitative review of the impact of HIT interventions on lipid management processes of care (screening or testing; drug initiation, titration or adherence; or referrals) or clinical outcomes (percent at low density lipoprotein cholesterol goal; absolute lipid levels; absolute risk scores; or cardiac hospitalizations) in outpatients with coronary heart disease or at increased risk. METHODS: PubMed and Google Scholar databases were searched using Medical Subject Headings related to clinical informatics and cholesterol or lipid management. English language articles that described a randomized controlled design, tested at least one HIT tool in high risk outpatients, and reported at least 1 lipid management process measure or clinical outcome, were included. RESULTS: Thirty-four studies that enrolled 87,874 persons were identified. Study ratings, outcomes, and magnitude of effects varied widely. Twenty-three trials reported a significant positive effect from a HIT tool on lipid management, but only 14 showed evidence that HIT interventions improve clinical outcomes. There was mixed evidence that provider-level computerized decision support improves outcomes. There was more evidence in support of patient-level tools that provide connectivity to the healthcare system, as well as system-level interventions that involve database monitoring and outreach by centralized care teams. CONCLUSION: Randomized controlled trials show wide variability in the effects of HIT on lipid management outcomes. Evidence suggests that multilevel HIT approaches that target not only providers but include patients and systems approaches will be needed to improve lipid treatment, adherence and quality

Rapid Diet Assessment Screening Tools for Cardiovascular Disease Risk Reduction across Healthcare Settings: A Scientific Statement from the American Heart Association

It is critical that diet quality be assessed and discussed at the point of care with clinicians and other members of the healthcare team to reduce the incidence and improve the management of diet-related chronic disease, especially cardiovascular disease. Dietary screening or counseling is not usually a component of routine medical visits. Moreover, numerous barriers exist to the implementation of screening and counseling, including lack of training and knowledge, lack of time, sense of futility, lack of reimbursement, competing demands during the visit, and absence of validated rapid diet screener tools with coupled clinical decision support to identify actionable modifications for improvement. With more widespread use of electronic health records, there is an enormous unmet opportunity to provide evidence-based clinician-delivered dietary guidance using rapid diet screener tools that must be addressed. In this scientific statement from the American Heart Association, we provide rationale for the widespread adoption of rapid diet screener tools in primary care and relevant specialty care prevention settings, discuss the theory- A nd practice-based criteria of a rapid diet screener tool that supports valid and feasible diet assessment and counseling in clinical settings, review existing tools, and discuss opportunities and challenges for integrating a rapid diet screener tool into clinician workflows through the electronic health record.

Proprotein convertase subtilisn/kexin type 9 inhibitors and small interfering RNA therapy for cardiovascular risk reduction: A systematic review and meta-analysis.

BackgroundAtherosclerotic cardiovascular disease (ASCVD) is the leading cause of mortality worldwide. Atherosclerosis occurs due to accumulation of low-density lipoprotein cholesterol (LDL-c) in the arterial system. Thus, lipid lowering therapy is essential for both primary and secondary prevention. Proprotein convertase subtilisn/kexin type 9 (PCSK9) inhibitors (Evolocumab, Alirocumab) and small interfering RNA (siRNA) therapy (Inclisiran) have been demonstrated to lower LDL-c and ASCVD events in conjunction with maximally tolerated statin therapy. However, the degree of LDL-c reduction and the impact on reducing major adverse cardiac events, including their impact on mortality, remains unclear.ObjectiveThe purpose of this study is to examine the effects of PCSK9 inhibitors and small interfering RNA (siRNA) therapy on LDL-c reduction and major adverse cardiac events (MACE) and mortality by conducting a meta-analysis of randomized controlled trials.MethodsUsing Pubmed, Embase, Cochrane Library and clinicaltrials.gov until April 2023, we extracted randomized controlled trials (RCTs) of PCSK9 inhibitors (Evolocumab, Alirocumab) and siRNA therapy (Inclisiran) for lipid lowering and risk of MACE. Using random-effects models, we pooled the relative risks and 95% CIs and weighted least-squares mean difference in LDL-c levels. We estimated odds ratios with 95% CIs among MACE subtypes and all-cause mortality. Fixed-effect model was used, and heterogeneity was assessed using the I2 statistic.ResultsIn all, 54 studies with 87,669 participants (142,262 person-years) met criteria for inclusion. LDL-c percent change was reported in 47 studies (n = 62,634) evaluating two PCSK9 inhibitors and siRNA therapy. Of those, 21 studies (n = 41,361) included treatment with Evolocumab (140mg), 22 (n = 11,751) included Alirocumab (75mg), and 4 studies (n = 9,522) included Inclisiran (284mg and 300mg). Compared with placebo, after a median of 24 weeks (IQR 12-52), Evolocumab reduced LDL-c by -61.09% (95% CI: -64.81, -57.38, pConclusionPCSK9 inhibitors (Evolocumab, Alirocumab) and siRNA therapy (Inclisiran) significantly reduced LDL-c by >40% in high-risk individuals. Additionally, both Alirocumab and Evolocumab reduced the risk of MACE, and Alirocumab reduced cardiovascular and all-cause mortality

The importance of low-density lipoprotein cholesterol measurement and control as performance measures: A joint clinical perspective from the national lipid association and the American society for preventive cardiology

Despite the established role of low-density lipoprotein cholesterol (LDL-C) as a major risk factor for cardiovascular disease (CVD), and the persistence of CVD as the leading cause of morbidity and mortality in the United States, national quality assurance metrics no longer include LDL-C measurement as a required performance metric. This clinical perspective reviews the history of LDL-C as a quality and performance metric and the events that led to its replacement. It also presents patient, healthcare provider, and health system rationales for re-establishing LDL-C measurement as a performance measure to improve cholesterol control in high-risk groups and to stem the rising tide of CVD morbidity and mortality, cardiovascular care disparities, and related healthcare cost

Enhancing the value of PCSK9 monoclonal antibodies by identifying patients most likely to benefit. A consensus statement from the National Lipid Association

Acquisition costs and cost-effectiveness have limited access and recommendations to use proprotein convertase subtilisin/kexin type 9 (PCSK9)–inhibiting monoclonal antibodies (mAbs). Recently, prices were reduced by 60% for alirocumab and evolocumab. This statement systematically reviewed subgroup analyses from statin and PCSK9 mAb trials to identify higher risk groups for which PCSK9 mAbs at the new price could be considered a reasonable (<US$100,000 per quality adjusted life year [QALY]) or high (<US$50,000 per QALY) value. In patients at extremely high risk, with a high burden of athersclerotic cardiovascular disease (ASCVD) or ASCVD with multiple poorly controlled or adverse risk factors, PCSK9 mAbs can provide reasonable value when low-density lipoprotein cholesterol (LDL-C) is ≥70 mg/dL. In patients at very high risk (ASCVD without peripheral arterial disease and lower levels of poorly controlled risk factors), PCSK9 mAbs provide a reasonable value when LDL-C levels are ≥100 mg/dL. High-risk patients (less-extensive ASCVD with well-controlled risk factors) may experience reasonable value when LDL-C levels are ≥130 mg/dL. Patients with heterozygous familial hypercholesterolemia or severe hypercholesterolemia with untreated LDL-C levels ≥220 mg/dL also should experience reasonable or high value from PCSK9 mAbs when LDL-C is ≥100 mg/dL for primary prevention and ≥70 mg/dL for secondary prevention. •Initial pricing limited uptake of highly effective proprotein convertase subtilisin/kexin type 9 monoclonal antibodies.•Recent price reductions call for new guidance in this National Lipid Association statement.•Value assessment may improve access to proprotein convertase subtilisin/kexin type 9 monoclonal antibodies for appropriate patient groups