Impact of Statin Therapy on Diabetes Incidence: Implications for Primary Prevention.

PURPOSE OF REVIEW: The present review aims to summarize current evidence, explore underlying mechanisms, and help guide clinicians regarding statin therapy and diabetes risk in primary prevention. RECENT FINDINGS: The observational and genetic epidemiology, as well as evidence from randomized controlled trials and meta-analyses, illustrate a modest, dose-dependent increase in risk of diabetes from statin therapy. Risk of new onset diabetes from statins appears to be greatest in those near the diagnostic threshold for diabetes or with diabetes risk factors prior to statin initiation. The risk of incident diabetes is vastly offset by the cardiovascular protection offered from statin therapy and should not deter guideline recommended statin initiation in primary prevention.

Effect of vigorous-intensity physical activity on incident cognitive impairment in high-risk hypertension.

INTRODUCTION: We investigated the effect vigorous physical activity (VPA) on the risk of incident mild cognitive impairment (MCI) and probable dementia among individuals with high-risk hypertension. METHODS: Baseline self-reported frequency of VPA was categorized into low VPA (<1 session/week), and high VPA (≥1 session/week). We used multivariate Cox regression analysis to examine the association of VPA categories with incident MCI and probable dementia events. RESULTS: Participants in the high VPA category, compared with low VPA, experienced lower events rates (per 1000 person-years) of MCI (13.9 vs 19.7), probable dementia (6.3 vs 9.0), and MCI/probable dementia (18.5 vs 25.8). In the multivariate Cox regression model, high VPA, compared with low VPA, was associated with lower risk of MCI, probable dementia, and MCI/probable dementia (HR [95% CI]: 0.81 [0.68-0.97], 0.80 [0.63-1.03], and 0.82 [0.70-0.96]), respectively. DISCUSSION: This study provides evidence that VPA may preserve cognitive function in high-risk patients with hypertension. HIGHLIGHTS: Hypertension is associated with an increased risk of cognitive impairment Physical activity (PA) is associated with a lower risk of decline in cognition The effect of ≥1 sessions of vigorous-intensity PA (VPA) per week was assessed This analysis included SPRINT MIND trial participants with high-risk hypertension ≥1 VPA sessions/week was associated with lower risk of future cognitive impairment.

Relationship Between Sarcopenia and Intensive Blood Pressure Control Efficacy and Safety: A Secondary Analysis of SPRINT.

BACKGROUND: Sarcopenia and hypertension are independently associated with worse cardiovascular disease (CVD) risk and survival. While individuals with sarcopenia may benefit from intensive blood pressure (BP) control, the increased vulnerability of this population raises concerns for potential harm. This study aimed to evaluate clinical and safety outcomes with intensive (target <120 mm Hg) versus standard (<140 mm Hg) systolic BP targets in older hypertensive adults with sarcopenia compared with nonsarcopenic counterparts in the SPRINT (Systolic Blood Pressure Intervention Trial). METHODS: Sarcopenia was defined using surrogates of the lowest sex-stratified median of the sarcopenia index (serum creatinine/cystatin C×100) for muscle wasting and gait speed ≤0.8 m/s for muscle weakness. Outcomes included CVD events, all-cause mortality, and serious adverse events. RESULTS: Of 2571 SPRINT participants with sarcopenia index and gait speed data available (aged ≥75 years), 502 (19.5%) met the criteria for sarcopenia, which was associated with higher risks of CVD events (adjusted hazard ratio, 1.49 [95% CI, 1.15-1.94]; P=0.003) and all-cause mortality (adjusted hazard ratio, 1.46 [95% CI, 1.09-1.94]; P=0.010). In participants with sarcopenia, intensive (versus standard) BP control nearly halved the risk of CVD events (adjusted hazard ratio, 0.57 [95% CI, 0.36-0.88]; P=0.012) without increasing serious adverse events. Similar risk reduction was seen for all-cause mortality in participants with sarcopenia (adjusted hazard ratio, 0.66 [95% CI, 0.41-1.08]; P=0.102), but the effect was only significant in those without chronic kidney disease. CONCLUSIONS: Older hypertensive adults with sarcopenia randomized to intensive BP control experienced a lower risk of CVD without increased adverse events compared with standard BP control. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01206062.

Small dense low-density lipoprotein cholesterol and coronary artery calcification in the Multi-Ethnic Study of Atherosclerosis.

AIMS: Elevated small dense LDL cholesterol (sd-LDL-C) increases atherosclerotic cardiovascular disease (CVD) risk. Although coronary artery calcification (CAC) is widely used for predicting CVD events, few studies have examined the relationship between sd-LDL-C and CAC. METHODS AND RESULTS: This study included 4672 individuals with directly measured baseline sd-LDL-C and CAC from the Multi-Ethnic Study of Atherosclerosis [mean (standard deviation) age: 61.9 (10.4) years; 52.5% women; 47.3% with baseline CAC (mean score >0)]. We used multi-variable general linear models and restricted cubic splines with the goodness of fit testing to evaluate the association of sd-LDL-C with the presence of CAC. Odds ratios [OR (95% confidence interval)] were adjusted for demographics and cardiovascular risk factors, including estimated total LDL-C. Higher quartiles of sd-LDL-C were associated with the presence of CAC, even after accounting for total LDL-C. Compared with the lowest quartile of sd-LDL-C, participants in Quartiles 2, 3, and 4 had higher odds for the presence of baseline CAC [Quartile 2 OR: 1.24 (1.00, 1.53); Quartile 3 OR: 1.51 (1.19, 1.93); and Quartile 4 OR 1.59 (1.17, 2.16)]. Splines suggested a quadratic curvilinear relationship of continuous sd-LDL-C with CAC after adjustment for demographics and CVD risk factors (quadratic vs. first-order sd-LDL-C terms likelihood ratio test: P = 0.015), but not after accounting for total LDL-C (quadratic vs. first-order terms: P = 0.156). CONCLUSION: In a large, multi-ethnic sample without known CVD, higher sd-LDL-C was associated with the presence of CAC, above and beyond total LDL-C. Whether selective direct measurement of sd-LDL-C is indicated to refine cardiovascular risk assessment in primary prevention warrants further investigation.

Higher levels of small dense particles of LDL cholesterol, better known as the 'bad cholesterol', are associated with a greater risk for the presence of coronary artery calcium, a strong marker for heart disease, even when accounting for estimated total (small dense + large body particles) LDL cholesterol.This risk is stronger in older individuals.Peak risk seems to occur between 49 and 71 mg/dL and does not increase further at higher levels.

Preventive Cardiovascular Care for Hypercholesterolemia in US Emergency Departments: A National Missed Opportunity.

BACKGROUND: Hypercholesterolemia (HCL) affects nearly half of Emergency Department (ED) patients who present with possible acute coronary syndrome (ACS). However, it is unknown whether US ED providers obtain lipid panels, calculate 10-year atherosclerotic cardiovascular disease (ASCVD) risk, and prescribe cholesterol-lowering medications for these patients. METHODS: We conducted a nationwide cross-sectional ED survey from April 18, 2023, to May 12, 2023. An electronic survey assessing current preventive HCL care practices for patients being evaluated for ACS. A convenience sample was obtained by sharing the survey with ED medical directors, chairs, and senior leaders using emergency medicine professional organization listservs and snowball sampling. Responding EDs were categorized as being associated with an academic medical center (AMC) or not (non-AMC). RESULTS: During the 4-week study period, 110 EDs (50 AMC and 60 non-AMC EDs) across 39 states responded. Just 1.8% (2/110) stated that their providers obtain a lipid panel on at least half of patients with possible ACS and only one ED (0.9%) responded that its providers calculate 10-year ASCVD risk and prescribe cholesterol medication for the majority of eligible patients. Most reported never obtaining lipid panels (60.9%, 67/110), calculating 10-year ASCVD risk (55.5%, 61/110), or prescribing cholesterol-lowering medications (52.7%, 58/110). CONCLUSIONS: The vast majority of US ED providers do not provide preventive cardiovascular care for patients presenting with possible ACS. Most ED providers do not evaluate for HCL, calculate ASCVD risk, or prescribe cholesterol-lowering medications for these patients.

Lipoprotein(a) and the pooled cohort equations for ASCVD risk prediction: The Multi-Ethnic Study of Atherosclerosis.

BACKGROUND AND AIMS: Lipoprotein(a) [Lp(a)] is an independent risk factor for atherosclerotic cardiovascular disease (ASCVD) but is not included in the Pooled Cohort Equations (PCE). We aimed to assess how well the PCE predict 10-year event rates in individuals with elevated Lp(a), and whether the addition of Lp(a) improves risk prediction. METHODS: We compared observed versus PCE-predicted 10-year ASCVD event rates, stratified by Lp(a) level and ASCVD risk category using Poisson regression, and evaluated the association between Lp(a) > 50 mg/dL and ASCVD risk using Cox proportional hazards models in the Multi-Ethnic Study of Atherosclerosis (MESA). We evaluated the C-index and net reclassification improvement (NRI) with addition of Lp(a) to the PCE. RESULTS: The study population included 6639 individuals (20%, n = 1325 with elevated Lp(a)). The PCE accurately predicted 10-year event rates for individuals with elevated Lp(a) with observed event rates falling within predicted limits. Elevated Lp(a) was associated with increased risk of CVD events overall (HR 1.27, 95% CI 1.00-1.60), particularly in low (HR 2.45, 95% CI 1.40-4.31), and high-risk (HR 1.41, 95% CI 1.02-1.96) individuals. Continuous NRI (95% CI) with the addition of Lp(a) to the PCE for CVD was 0.0963 (0.0158-0.1953) overall, and 0.2999 (0.0876, 0.5525) among low-risk individuals. CONCLUSIONS: The PCE performs well for event rate prediction in individuals with elevated Lp(a). However, Lp(a) is associated with increased CVD risk, and the addition of Lp(a) to the PCE improves risk prediction, particularly among low-risk individuals. These results lend support for increasing use of Lp(a) testing for risk assessment.

Proprotein Convertase Subtilisin/Kexin Type 9 Inhibition: The Big Step Forward in Lipid Control.

The breakthrough discovery of proprotein convertase subtilisin/kexin type 9 (PCSK9) 20 years ago revolutionised the current understanding of cholesterol homeostasis. Genetic studies have shown that gain-of-function mutations in PCSK9 lead to elevated LDL cholesterol and increased risk of atherosclerotic cardiovascular disease, while loss-of-function mutations in PCSK9 result in lifelong low levels of circulating LDL cholesterol and dramatic reduction in atherosclerotic cardiovascular disease. Therapies inhibiting PCSK9 lead to a higher density of LDL receptor on the surface of hepatocytes, resulting in greater ability to clear circulating LDL. Thus far, randomised controlled trials have shown that subcutaneous fully human monoclonal antibodies targeting PCSK9, evolocumab and alirocumab, and PCSK9 silencing with inclisiran result in drastic reductions in LDL cholesterol. Additionally, several novel strategies to target PCSK9 are in development, including oral antibody, gene silencing, DNA base editing and vaccine therapies. This review highlights the efficacy, safety and clinical use of these various approaches in PCSK9 inhibition.

Estrogen-Based Gender-Affirming Hormone Therapy and Subclinical Cardiovascular Disease in Transgender Women with HIV.

Purpose: Transgender women (TW) are disproportionately affected by HIV infection and cardiovascular disease (CVD). This study evaluated whether estrogen-based gender-affirming hormone therapy (GAHT) in TW with HIV (TWH-GAHT) is associated with indices of subclinical CVD. Methods: Of the 40 HIV-seropositive persons enrolled, 20-60 years of age, on antiretroviral treatment with undetectable viral load, assessments were performed on 15 TWH; of these persons, 11 were GAHT treated. These TWH-GAHT were matched with HIV+ cisgender men and women based on age, ethnicity/race, body mass index, and antihypertensive medication use. Sex hormones, and cardiometabolic (waist circumference, blood pressure, insulin resistance, lipid profile, and C-reactive protein), vascular (flow-mediated dilation [FMD] and arterial stiffness), and proinflammatory measures were obtained. Results: TWH-GAHT displayed elevated estradiol and suppressed testosterone levels relative to normative ranges. Analyses indicated the TWH-GAHT displayed lower low-density lipoprotein compared with cisgender groups (p < 0.05). Although no difference was seen on FMD, the central augmentation index of aortic stiffness was higher in cisgender HIV+ women than cisgender HIV+ men (p < 0.05). No other group difference on subclinical CVD markers was observed. For TWH, partial correlations indicated associations of certain sex hormones with selected cardiometabolic outcomes and the inflammatory cytokine, interleukin-8. Conclusion: When well matched to HIV+ cisgender men and women, subclinical CVD pathophysiology did not appear elevated in TWH-GAHT, although tendencies emerged suggesting that some subclinical CVD indices may be higher, but others lower than cisgender groups. Longitudinal studies of TWH are needed to more precisely evaluate the moderating effect of GAHT on cardiometabolic pathophysiology.

Emergency Department Observation Unit Patients Want Evaluation and Treatment for Hypercholesterolemia: A Health Belief Model Study.

BACKGROUND: Hypercholesterolemia (HCL) is common among emergency department (ED) and ED observation unit (EDOU) patients with chest pain but is not typically addressed in these settings. The objective of this study was to assess patient attitudes towards EDOU-based HCL care using the Health Belief Model. METHODS: We conducted a cross-sectional survey study among 100 EDOU patients ≥18 years-old evaluated for chest pain in the EDOU of a tertiary care center from September 1, 2020, to November 01, 2021. Five-point Likert-scale surveys were used to assess each Health Belief Model domain: Cues to Action, Perceived Susceptibility, Perceived Barriers, Perceived Self-Efficacy, and Perceived Benefits. Responses were categorized as agree or do not agree. RESULTS: The participants were 49.0% (49/100) female, 39.0% (39/100) non-white, and had a mean age of 59.0 ± 12.4 years. Most (83.0% [83/100, 95% confidence interval (CI), 74.2%-89.8%]) agreed the EDOU is an appropriate place for HCL education and 52.0% (52/100, 95% CI, 41.8%-62.1%) were interested in talking with their EDOU care team about HCL. Regarding Perceived Susceptibility, 88.0% (88/100, 95% CI, 80.0%-93.6%) believed HCL to be bad for their health, while 41.0% (41/100, 95% CI, 31.3%-51.3%) believed medication costs could be a barrier. For Perceived Self-Efficacy, 76.0% (76/100, 95% CI, 66.4%-84.0%) were receptive to taking medications. Overall, 95.0% (95/100, 95% CI, 88.7%-98.4%) believed managing HCL would benefit their health. CONCLUSIONS: This Health Belief Model-based survey indicates high patient interest in EDOU-initiated HCL care. Patients reported high rates of Perceived Susceptibility, Self-Efficacy, and Benefits and a minority found HCL therapy costs a barrier.

Rarely tested or treated but highly prevalent: Hypercholesterolemia in ED observation unit patients with chest pain.

BACKGROUND: Hypercholesterolemia (HCL) is common among Emergency Department (ED) patients with chest pain but is typically not addressed in this setting. This study aims to determine whether a missed opportunity for Emergency Department Observation Unit (EDOU) HCL testing and treatment exists. METHODS: We conducted a retrospective observational cohort study of patients ≥18 years old evaluated for chest pain in an EDOU from 3/1/2019-2/28/2020. The electronic health record was used to determine demographics and if HCL testing or treatment occurred. HCL was defined by self-report or clinician diagnosis. Proportions of patients receiving HCL testing or treatment at 1-year following their ED visit were calculated. HCL testing and treatment rates at 1-year were compared between white vs. non-white and male vs. female patients using multivariable logistic regression models including age, sex, and race. RESULTS: Among 649 EDOU patients with chest pain, 55.8% (362/649) had known HCL. Among patients without known HCL, 5.9% (17/287, 95% CI 3.5-9.3%) had a lipid panel during their index ED/EDOU visit and 26.5% (76/287, 95% CI 21.5-32.0%) had a lipid panel within 1-year of their initial ED/EDOU visit. Among patients with known or newly diagnosed HCL, 54.0% (229/424, 95% CI 49.1-58.8%) were on treatment within 1-year. After adjustment, testing rates were similar among white vs. non-white patients (aOR 0.71, 95% CI 0.37-1.38) and men vs. women (aOR 1.32, 95% CI 0.69-2.57). Treatment rates were similar among white vs. non-white (aOR 0.74, 95% CI 0.53-1.03) and male vs. female (aOR 1.08, 95% CI 0.77-1.51) patients. CONCLUSIONS: Few patients were evaluated for HCL in the ED/EDOU or outpatient setting after their ED/EDOU encounter and only 54% of patients with HCL were on treatment during the 1-year follow-up period after the index ED/EDOU visit. These findings suggest a missed opportunity to reduce cardiovascular disease risk exists by evaluating and treating HCL in the ED or EDOU.

Chest pain observation unit: A missed opportunity to initiate smoking cessation therapy.

BACKGROUND: Emergency Department Observation Unit (EDOU) patients with chest pain have a high prevalence of smoking, a key cardiovascular disease risk factor. While in the EDOU, there is an opportunity to initiate smoking cessation therapy (SCT), but this is not standard practice. This study aims to describe the missed opportunity for EDOU-initiated SCT by determining the proportion of smokers who receive SCT in the EDOU and within 1-year of EDOU discharge and to evaluate if SCT rates vary by race or sex. METHODS: We performed an observational cohort study of patients ≥18 years old being evaluated for chest pain in a tertiary care center EDOU from 3/1/2019-2/28/2020. Demographics, smoking history, and SCT were determined by electronic health record review. Emergency, family medicine, internal medicine, and cardiology records were reviewed to determine if SCT occurred within 1-year of their initial visit. SCT was defined as behavioral interventions or pharmacotherapy. Rates of SCT in the EDOU, 1-year follow-up period, and the EDOU through 1-year of follow-up were calculated. SCT rates from the EDOU through 1-year were compared between white vs. non-white and male vs. female patients using a multivariable logistic regression model including age, sex, and race. RESULTS: Among 649 EDOU patients, 24.0% (156/649) were smokers. These patients were 51.3% (80/156) female and 46.8% (73/156) white, with a mean age of 54.4 ± 10.5 years. From the EDOU encounter through 1-year of follow-up, only 33.3% (52/156) received SCT. In the EDOU, 16.0% (25/156) received SCT. During the 1-year follow-up period, 22.4% (35/156) had outpatient SCT. After adjusting for potential confounders, SCT rates from the EDOU through 1-year were similar among whites vs. non-whites (aOR 1.19, 95% CI 0.61-2.32) and males vs. females (aOR 0.79, 95% CI 0.40-1.56). CONCLUSIONS: SCT was rarely initiated in the EDOU among chest pain patients who smoke and most patients who did not receive SCT in the EDOU never received SCT at 1-year of follow-up. Rates of SCT were similarly low among race and sex subgroups. These data suggest an opportunity exists to improve health by initiating SCT in the EDOU.

Association of Lp(a) (Lipoprotein[a]) and Hypertension in Primary Prevention of Cardiovascular Disease: The MESA.

BACKGROUND: This study explored the longitudinal relationship of Lp(a) (lipoprotein[a]) and hypertension to cardiovascular outcomes in a large multiethnic cohort free of baseline cardiovascular disease. METHODS: Individuals from the MESA (Multi-Ethnic Study of Atherosclerosis; N=6674) were grouped as follows: group 1: Lp(a) <50 mg/dL and no hypertension; group 2: Lp(a) ≥50 mg/dL and no hypertension; group 3: Lp(a) <50 mg/dL and hypertension; and group 4: Lp(a) ≥50 mg/dL and hypertension. Kaplan-Meier curves and multivariable Cox proportional hazard models were used to assess the relationship of Lp(a) and hypertension with time to cardiovascular disease events. RESULTS: Mean follow-up time was 13.9 (5.0) years and 809 participants experienced a cardiovascular disease event. A statistically significant interaction was found between Log[Lp(a)] and hypertension status (P=0.091). Compared with the reference group (Lp[a] <50 mg/dL and no hypertension), those with Lp[a] ≥50 mg/dL and no hypertension had no increased risk for cardiovascular disease events (hazard ratio, 1.09 [95% CI, 0.79-1.50]). However, those with Lp(a) <50 mg/dL and hypertension or Lp(a) ≥50 mg/dL and hypertension demonstrated a statistically significant increase in risk compared to the reference group (hazard ratio, 1.66 [95% CI, 1.39-1.98]) and (hazard ratio, 2.07 [95% CI, 1.63-2.62]), respectively. Among those with hypertension, Lp(a) was associated with a significant increase in cardiovascular disease risk (hazard ratio, 1.24 [95% CI, 1.01-1.53]). CONCLUSIONS: Although the major contribution to cardiovascular risk was hypertension, elevated Lp(a) significantly modified the association of hypertension with cardiovascular disease. More research is needed to understand mechanistic links among Lp(a), hypertension, and cardiovascular disease.

Familial Hypercholesterolemia: From Clinical Suspicion to Novel Treatments.

Familial hypercholesterolemia (FH) is the most common monogenic disorder in humans. It affects millions of people globally, increasing the risk of developing cardiovascular disease (CVD) at a younger age due to elevated levels of low-density lipoprotein cholesterol (LDL-C) from birth. While effective traditional and novel treatments are available, the most significant challenge with FH is the lack of timely diagnosis. As a result, many patients remain undertreated leading to an increased risk of CVD. To mitigate risk, initiating early and aggressive LDL-C-lowering therapies is recommended. Moreover, given its autosomal dominant inheritance patterns, it is also recommended to perform cascade lipid and/or genetic testing of all first-degree relatives. This review highlights the importance of early FH diagnosis and available treatment options. Greater awareness and improved screening efforts can help diagnose and treat more individuals, ultimately reducing the CVD risk associated with FH.

Assessment of Atherosclerotic Cardiovascular Disease Risk in Primary Prevention.

PURPOSE: The objective of this report was to review the application of the pooled cohort equations in primary prevention and the assessment of cardiovascular health. REVIEW METHODS: Literature review was conducted using the PubMed database. In addition, the 2018 Multi-Society Guidelines on Management of Blood Cholesterol and the 2019 American College of Cardiology/American Heart Association Guidelines on the Primary Prevention of Cardiovascular Disease were reviewed. SUMMARY: Primary prevention refers to individuals with no history of atherosclerotic cardiovascular disease, severe hypercholesterolemia, or diabetes. For these adults, aged 40-75 yr, who have a low-density lipoprotein-cholesterol of ≥70 mg/dL and <190 mg/dL, the pooled cohort equations should be used to provide a quantitative assessment of 10-yr atherosclerotic cardiovascular disease risk. From here, individuals are grouped as low risk (<5%), borderline risk (5 to <7.5%), intermediate risk (7.5 to <20%), or high risk (≥20%). Statin therapy should be strongly advised in those with an atherosclerotic cardiovascular disease risk of ≥20%, while statin therapy can be considered in those with a risk between 5% and <20%, especially if risk enhancing factors are present. If uncertainty still exists regarding treatment, a coronary artery calcium score can help further refine risk. All individuals, regardless of atherosclerotic cardiovascular disease risk, should have a cardiovascular health assessment using Life's Essential 8, which includes diet, physical activity, nicotine exposure, body mass index, blood glucose, blood lipids, blood pressure, and sleep.

Relationship of low-density lipoprotein-cholesterol and lipoprotein(a) to cardiovascular risk: The Multi-Ethnic Study of Atherosclerosis (MESA).

BACKGROUND AND AIMS: Plasma low-density lipoprotein cholesterol (LDL-C) and lipoprotein(a) (Lp(a)) are both associated with coronary heart disease (CHD). This study investigated whether elevated plasma Lp(a) concentration was associated with increased CHD risk when LDL-C was low (≤100 mg/dL) in individuals not on statin therapy. METHODS: Participants from the Multi-Ethnic Study of Atherosclerosis (MESA) (n = 4,585) were categorized into four groups: Group 1: LDL-C ≤ 100 mg/dL, Lp(a) < 50 mg/dL; Group 2: LDL-C > 100 mg/dL, Lp(a) < 50 mg/dL; Group 3: LDL-C ≤ 100 mg/dL, Lp(a) ≥ 50 mg/dL; and Group 4: LDL-C > 100 mg/dL, Lp(a) ≥ 50 mg/dL. The relationship of Lp(a) and LDL-C with time to CHD events was assessed with Kaplan Meier curves and multivariable Cox proportional hazard models. RESULTS: Participants were followed for a mean of 13.4 years and a total of 315 CHD events occurred. Compared to participants with LDL-C ≤ 100 mg/dL and Lp(a) < 50 mg/dL, those with LDL-C > 100 mg/dL and Lp(a) < 50 mg/dL (Group 2) demonstrated no increased risk for CHD events (HR: 0.92; 95% CI: 0.69, 1.21). However, participants with LDL-C ≤ 100 mg/dL and Lp(a) ≥ 50 mg/dL (Group 3) and those with LDL-C > 100 mg/dL and Lp(a) ≥ 50 mg/dL (Group 4) exhibited significantly increased risk of CHD events compared to Group 1 (HR: 1.83; 95% CI: 1.02, 3.27) and Group 2 (HR: 1.61; 95% CI: 1.15, 2.26), respectively. CONCLUSIONS: When Lp(a) was elevated, risk of CHD events increased, regardless of baseline LDL-C.

Newer and Emerging LDL-C Lowering Agents and Implications for ASCVD Residual Risk.

Multiple lines of evidence demonstrate that low-density lipoprotein-cholesterol causes atherosclerotic cardiovascular disease. Thus, targeting and lowering low-density lipoprotein-cholesterol is the principal strategy to reduce cardiovascular disease risk in primary and secondary prevention. Statin therapy is the foundation of lipid-lowering treatment, but adherence rates are low, and many individuals do not attain target low-density lipoprotein-cholesterol values. Additionally, most statin-treated patients are still at considerable atherosclerotic cardiovascular disease risk, emphasizing the need for more aggressive low-density lipoprotein-cholesterol-lowering therapies. The purpose of this review is to discuss new and emerging approaches to further lower low-density lipoprotein-cholesterol, including inhibition of ATP-citrate lyase, proprotein convertase subtilisin-kexin type 9, angiopoietin-related protein 3, and cholesteryl ester transfer protein.

Better prediction of stroke in atrial fibrillation with incorporation of cancer in CHA2DS2VASC score: CCHA2DS2VASC score.

Introduction: Atrial fibrillation (AF) is associated with an increased risk of stroke. Despite evidence linking cancer and thrombosis, cancer is not part of the CHA2DS2VASc score. Hypothesis: Cancer is an independent risk factor for thromboembolic stroke in patients with AF. Method: The SEER database was utilized to identify patients with lung, colon, breast, and prostate cancers with AF and no prior diagnosis of stroke and. compared to controls within the dataset. The primary endpoint was rates of stroke per 100 person-years. Cox regression modeling and a nested model comparing CHA2DS2VASc score (Model 1) with a complete model including cancer diagnosis (Model 2) were performed. Models were compared using Akaike Information Criterion (AIC) and Net Reclassification Index (NRI). A propensity-matched cohort with equivalent CHA2DS2VASc scores determining stroke-free survival was also performed. Results: A total of 101,185 patients were included in the analysis, with 48,242 in the Cancer and 52,943 in the Non-cancer Group. Stroke rate per 100 person-years was significantly higher in the Cancer Group. The CHA2DS2VASc model (Model 1) was compared against a model including cancer (Model 2) showing improved predictability as assessed by both NRI and AIC. Cox regression analysis calculated a hazard ratio of 1.085 for Cancer, which was comparable to age >75, female sex, and diabetes. Propensity matched Kaplan-Meier curve demonstrated a decreased probability of stroke-free survival in the Cancer Group. Conclusion: Cancers increase the risk of stroke in patients with AF. Consideration should be given to the addition of cancer to the clinical scoring system.

Abacavir antiretroviral therapy and indices of subclinical vascular disease in persons with HIV.

OBJECTIVE: Indices of cardiovascular disease (CVD) risk, vascular endothelial dilation, arterial stiffness and endothelial repair were examined in persons with HIV (PWH) on an antiretroviral therapy (ART) that included abacavir (ABC+) in comparison with PWH on ART without abacavir (ABC-), and with HIV seronegative (HIV-) individuals. APPROACH: The 115 participants (63% men), aged 30-50 years, did not have CVD, metabolic, endocrine, or chronic renal conditions. PWH were on stable ART for six-months or more. Vascular assessments included flow-mediated dilation (FMD), aortic, radial and femoral arterial stiffness (cAIx, crPWV, cfPWV), and thigh and calf arterial compliance (Vmax50). Endothelial repair was indexed by endothelial progenitor cell colony forming units (EPC-CFU). Traditional CVD risk measures included blood pressure, central adiposity, lipids, insulin resistance (HOMA-IR), CRP and ASCVD score. Analyses controlled for demographics (age, sex, education), medications (antihypertensive, statin/fibrate, antipsychotic), and substance abuse (ASSIST). RESULTS: No group differences were observed in central adiposity, HOMA-IR, CRP, or ASCVD risk score. However, the ABC- group displayed greater dyslipidemia. The ABC+ group displayed no difference on FMD, cAIx, cfPWV or calf Vmax50 compared with other groups. When CD4 count and viral load were controlled, no additional differences between the ABC+ and ABC- groups emerged. Analyses of crPWV and thigh Vmax50 suggested supported by a trend toward lower EPC-CFU in the HIV+ groups than the HIV- group. CONCLUSIONS: Findings indicate that ABC treatment of 30-50 year-old PWH on stable ART is not likely to contribute in a robust way to higher CVD risk.

Immune Checkpoint Inhibitors Mediated Lymphocytic and Giant Cell Myocarditis: Uncovering Etiological Mechanisms.

The advent of immune checkpoint inhibitors (ICIs) has revolutionized the field of oncology, but these are associated with immune related adverse events. One such adverse event, is myocarditis, which has limited the continued immunosuppressive treatment options in patients afflicted by the disease. Pre-clinical and clinical data have found that specific ICI targets and precipitate distinct myocardial infiltrates, consistent with lymphocytic or giant cell myocarditis. Specifically, it has been reported that CTLA-4 inhibition preferentially results in giant cell myocarditis with a predominately CD4+ T cell infiltrate and PD-1 inhibition leads to lymphocytic myocarditis, with a predominately CD8+ T cell infiltrate. Our manuscript discusses the latest literature surrounding ICI pathways and targets, while detailing proposed mechanisms behind ICI mediated myocarditis.