PURPOSE OF REVIEW: Lipoprotein(a) [Lp(a)] is causally associated with cardiovascular diseases, and elevated levels are highly prevalent. However, there is a lack of available therapies to address Lp(a)-mediated risk. Though aspirin has progressively fallen out of favor for primary prevention, individuals with high Lp(a) may represent a high-risk group that derives a net benefit. RECENT FINDINGS: Aspirin has been demonstrated to have a clear benefit in secondary prevention of cardiovascular disease, but recent primary prevention trials have at best demonstrated a small benefit. However, individuals with elevated Lp(a) may be of high risk enough to benefit, particularly given interactions between Lp(a) and the fibrinolytic system / platelets, and the lack of available targeted medical therapies. In secondary analyses of the Womens Health Study (WHS) and the Aspirin in Reducing Events in the Elderly (ASPREE) trial, aspirin use was associated with a significant reduction in cardiovascular events in carriers of genetic polymorphisms associated with elevated Lp(a) levels. Further studies are needed, however, as these studies focused on narrower subsets of the overall population and genetic markers. SUMMARY: Individuals with elevated Lp(a) may benefit from aspirin therapy in primary prevention, but further study with plasma Lp(a) levels, broader populations, and randomization of aspirin are needed.

Lipoprotein(a) (Lp(a)) is an established risk factor for multiple cardiovascular diseases. Several lines of evidence including mechanistic, epidemiologic, and genetic studies support the role of Lp(a) as a causal risk factor for atherosclerotic cardiovascular disease (ASCVD) and aortic stenosis/calcific aortic valve disease (AS/CAVD). Limited therapies currently exist for the management of risk associated with elevated Lp(a), but several targeted therapies are currently in various stages of clinical development. In this review, we detail evidence supporting Lp(a) as a causal risk factor for ASCVD and AS/CAVD, and discuss approaches to managing Lp(a)-associated risk.

Objective

Methamphetamine use is associated with systolic dysfunction, pulmonary arterial hypertension and may also be associated with diastolic dysfunction. The impact of methamphetamine cessation on methamphetamine-associated heart failure (MethHF) remains poorly characterised. We aimed to longitudinally characterise methamphetamine-associated heart failure patients with reduced (METHrEF) and preserved (METHpEF) left ventricular ejection fraction (EF), and evaluate the relationship between methamphetamine cessation and clinical outcomes.

Methods

We performed a retrospective cohort study, and reviewed medical records of patients with METHrEF, METHpEF and heart failure controls without methamphetamine use. Echocardiographic variables were recorded for up to 12 months, with clinical follow-up extending to 24 months.

Results

Among METHrEF patients (n=28, mean age 51±9 years, 82.1% male), cessation was associated with improvement in EF (+10.6±13.1%, p=0.009) and fewer heart failure admissions per year compared with continued use (median 0.0, IQR 0.0-1.0 vs median 2.0, IQR 1.0-3.0, p=0.039). METHpEF patients (n=28, mean age 50±8 years, 60.7% male) had higher baseline right ventricular systolic pressure (median 53.44, IQR 43.70-84.00 vs median 36.64, IQR 29.44-45.95, p=0.011), and lower lateral E/E' ratio (8.1±3.6 vs 11.2±4., p<0.01) compared with controls (n=32). Significant improvements in echocardiographic parameters and clinical outcomes were not observed following cessation in this group.

Conclusions

METHrEF patients who cease methamphetamine use have significant improvement in left ventricular systolic function and fewer heart failure admissions, suggesting that METHrEF may be reversible. Echocardiographic parameters suggest that some patients with METHpEF may have pulmonary hypertension in the absence of overt signs of left ventricular diastolic dysfunction, but additional study is needed to characterise this patient cohort.

Background Despite its high prevalence and clinical significance, clinical measurement of lipoprotein(a) is rare but has not been systematically quantified. We assessed the prevalence of lipoprotein(a) testing overall, in those with various cardiovascular disease (CVD) conditions and in those undergoing cardiac testing across 6 academic medical centers associated with the University of California, in total and by year from 2012 to 2021. Methods and Results In this observational study, data from the University of California Health Data Warehouse on the number of individuals with unique lipoprotein(a) testing, unique CVD diagnoses (using International Classification of Diseases, Tenth Revision [ICD-10], codes), and other unique cardiac testing were collected. The proportion of total individuals, the proportion of individuals with a given CVD diagnosis, and the proportion of individuals with a given cardiac test and lipoprotein(a) testing any time during the study period were calculated. From 2012 to 2021, there were 5 553 654 unique adults evaluated in the University of California health system, of whom 18 972 (0.3%) had lipoprotein(a) testing. In general, those with lipoprotein(a) testing were more likely to be older, men, and White race, with a greater burden of CVD. Lipoprotein(a) testing was performed in 6469 individuals with ischemic heart disease (2.9%), 836 with aortic stenosis (3.1%), 4623 with family history of CVD (3.3%), 1202 with stroke (1.7%), and 612 with coronary artery calcification (6.1%). For most conditions, the prevalence of testing in the same year as the diagnosis of CVD was relatively stable, with a small upward trend over time. Lipoprotein(a) testing was performed in 10 753 individuals (1.8%) who had lipid panels, with higher rates with more specialized testing, including coronary computed tomography angiography (6.8%) and apolipoprotein B (63.0%). Conclusions Lipoprotein(a) testing persists at low rates, even among those with diagnosed CVD, and remained relatively stable over the study period.

Hypertension (HTN) is a well-established risk factor for cardiovascular diseases (CVDs), including ischemic heart disease, stroke, heart failure, and atrial fibrillation. The prevalence of HTN, as well as mortality rates attributable to HTN, continue to increase, particularly in the United States and among Black populations. The risk of HTN involves a complex interaction of genetics and modifiable risk factors, including dietary patterns. In this regard, there is accumulating evidence that links dietary intake of red meat with a higher risk of poorly controlled blood pressure and HTN. However, research on this topic contains significant methodological limitations, which are described in the review. The report provided below also summarizes the available research reports, with an emphasis on processed red meat consumption and how different dietary patterns among certain populations may contribute to HTN-related health disparities. Finally, this review outlines potential mechanisms and provides recommendations for providers to counsel patients with evidence-based nutritional approaches regarding red meat and the risk of HTN, as well as CVD morbidity and mortality.

Background

The Agatston coronary artery calcium (CAC) score provides robust cardiovascular disease risk prediction but upweights plaque area by a density factor. Density, however, has been shown to be inversely associated with events. Using CAC volume and density separately improves risk prediction, but it is unclear how to apply this method clinically. We aimed to evaluate the association between CAC density and cardiovascular disease across the spectrum of CAC volume to better understand how to incorporate these metrics into a single score.

Methods

We performed an analysis of MESA (Multi-Ethnic Study of Atherosclerosis) participants with detectable CAC to evaluate the association between CAC density and events by level of CAC volume using multivariable Cox regression models.

Results

In a cohort of 3316 participants, there was a significant interaction (P<0.001) between CAC volume and density for coronary heart disease (CHD) risk (myocardial infarction, CHD death, resuscitated cardiac arrest). Models using CAC volume and density resulted in improvement in the C-index (0.703, SE 0.012 versus 0.687, SE 0.013) and a significant net reclassification improvement (0.208 [95% CI, 0.102-0.306]) compared with the Agatston score for CHD risk prediction. Density was significantly associated with lower CHD risk at volumes ≤130 mm³ (hazard ratio, 0.57 per unit of density [95% CI, 0.43-0.75]), but the inverse association at volumes >130 mm³ was not significant (hazard ratio, 0.82 per unit of density [95% CI, 0.55-1.22]).

Conclusions

The lower risk for CHD associated with higher CAC density varied by level of volume, and volume ≤130 mm³ is a potentially clinically useful cut point. Further study is needed to integrate these findings into a unified CAC scoring method.

BACKGROUND: Lipid-lowering therapy (LLT) plays a central role in managing atherosclerotic cardiovascular disease (ASCVD) risk, but its underuse is reported in over 40% of the qualified population in the United States. Studies on factors, particularly actionable factors associated with guideline-directed LLT are limited. METHODS: This study evaluated participants from the Multi-Ethnic Study of Atherosclerosis (MESA) on their qualification for LLT at exam 5 (2010-2012) according to the 2013 American College of Cardiology (ACC)/American Heart Association (AHA) guideline on cholesterol management. Participants were categorized as on-LLT or off-LLT at the following exam (2016-2018). Multi-variable relative risk (RR) models were used to analyze between LLT usage and factors prior to 2013, including age, gender, race/ethnicity, education level and medical insurance, income, smoking, body mass index (BMI), diabetes, hypertension, and presence of coronary artery calcium (CAC). RESULTS: Among the 2114 participants qualified for LLT at exam 5 with an average age of 70.7, 1,129 (53.4%) were on LLT while 985 (46.6%) were off LLT at exam 6. Black participants were less likely to be on LLT compared to the reference white participants (RR 0.80, 95% confidence interval CI 0.71-0.90). Higher BMI showed borderline significant association with LLT. Comorbidities of diabetes and hypertension were positively associated with LLT use (RR 1.39 and 1.23, 95% CI 1.27-1.52 and 1.10-1.36, respectively). CAC score > 0 as an indicator of subclinical ASCVD was strongly associated with LLT too, independent of other demographic or comorbidity factors (RR 1.38, 95% CI 1.21-1.56). CONCLUSIONS: This study identifies key factors influencing LLT use among MESA participants. Black participants were less likely to be on LLT, highlighting healthcare disparities. CAC presence was strongly associated with LLT use, suggesting that CAC measurement could be an actionable factor to improve adherence to LLT guidelines.

Background

Effective therapies for reducing cardiovascular disease (CVD) risk in people with elevated lipoprotein(a) are lacking, especially for primary prevention. Because of the potential association of lipoprotein(a) with thrombosis, we evaluated the relationship between aspirin use and CVD events in people with elevated lipoprotein(a).

Methods and results

We used data from the MESA (Multi-Ethnic Study of Atherosclerosis), a prospective cohort study of individuals free of baseline cardiovascular disease. Due to potential confounding by indication, we matched aspirin users to nonusers using a propensity score based on CVD risk factors. We then evaluated the association between aspirin use and coronary heart disease (CHD) events (CHD death, nonfatal myocardial infarction) stratified by baseline lipoprotein(a) level (threshold of 50 mg/dL) using Cox proportional hazards models with adjustment for CVD risk factors. After propensity matching, the study cohort included 2183 participants, including 1234 (57%) with baseline aspirin use and 423 (19%) with lipoprotein(a) >50 mg/dL. Participants with lipoprotein(a) >50 mg/dL had a higher burden of CVD risk factors, more frequent aspirin use (61.7% versus 55.3%, P=0.02), and higher rate of incident CHD events (13.7% versus 8.9%, P<0.01). Aspirin was associated with a significant reduction in CHD events among those with elevated lipoprotein(a) (hazard ratio, 0.54 [95% CI, 0.32-0.94]; P=0.03). Those with lipoprotein(a) >50 mg/dL and aspirin use had similar CHD risk as those with lipoprotein(a) ≤50 mg/dL regardless of aspirin use.

Conclusions

Aspirin use was associated with a significantly lower risk for CHD events in participants with lipoprotein(a) >50 mg/dL without baseline CVD. The results of this observational propensity-matched study require confirmation in studies with randomization of aspirin use.

Background

We aimed to evaluate for occult systolic dysfunction and the effect of methamphetamine cessation among patients with methamphetamine use (MU) and heart failure with preserved ejection fraction (HFpEF).

Methods

A retrospective cohort of patients with HFpEF with serial echocardiograms was stratified by MU and evaluated using myocardial strain analysis on echocardiograms at baseline and 1 year to measure global longitudinal strain (GLS). Contemporaneous controls with an ICD diagnosis of HF within 3 days of an MU case were chosen.

Results

Patients with MU (n = 31) were younger (49 ± 10 vs 59 ± 16 years, p < 0.01) and more frequently male (55% vs 26%, p = 0.04) than controls (n = 23). There was no baseline difference in ejection fraction (EF) (median 66% [IQR 58,71%] vs 62% [56,69%], p = 0.33) or GLS (-13.0% [-16.3,-10.9%] vs -14.8% [-16.0,-11.3%], p = 0.40). At one-year follow-up, MU cessation (n = 15) was associated with improvement in GLS (absolute change -4.4% [-6.5,-1.7%], p < 0.01), while no absolute change was observed with continued MU (n = 16) (0.74% [-1.2,2.8%], p = 0.22) or controls without MU (-0.6% [-2.1,2.8%], p = 0.78). Of those with abnormal baseline GLS, normalization was observed in 46% with MU cessation, none with continued MU, and 5% of controls (p < 0.001). Among MU patients, improvement in GLS was associated with decreased HF admissions per year [HR 0.74 per 1% change in GLS, 95% CI 0.55,0.98, p = 0.04].

Conclusions

Patients with MU and HFpEF may have occult systolic dysfunction as demonstrated by abnormal GLS, and MU cessation at 1 year is associated with improvement in GLS and a reduction in risk of HF admissions.

Background

The burden of substance abuse among patients with heart failure and its association with subsequent emergency department visits and hospital admissions are poorly characterized.

Methods

We evaluated the medical records of patients with a diagnosis of heart failure treated at the University of California-San Diego from 2005 to 2016. We identified substance abuse via diagnosis codes or urine drug screens. We used Poisson regression to evaluate the incidence rate ratios (IRR) of substance abuse for emergency department visits or hospitalizations with a primary diagnosis of heart failure, adjusted for age, sex, race, medical insurance status, and medical diagnoses.

Results

We identified 11,268 patients with heart failure and 15,909 hospital encounters for heart failure over 49,712 person-years of follow-up. Substance abuse was diagnosed in 15.2% of patients. Disorders such as methamphetamine abuse (prevalence 5.2%, IRR 1.96, 95% confidence interval [CI] 1.85-2.07), opioid use and abuse (8.2%, IRR 1.54, 95% CI 1.47-1.61), and alcohol abuse (4.5%, IRR 1.51, 95% CI 1.42-1.60) were associated with a greater number of hospital encounters for heart failure, with associations that were comparable to diagnoses such as atrial fibrillation (37%, IRR 1.78, 95% CI 1.73-1.84), ischemic heart disease (24%, IRR 1.67, 95% CI 1.62-1.73), and chronic kidney disease (26%, IRR 1.57, 95% CI 1.51-1.62).

Conclusions

Although less prevalent than common medical comorbidities in patients with heart failure, substance-abuse disorders are significant sources of morbidity that are independently associated with emergency department visits and hospitalizations for heart failure. Greater recognition and treatment of substance abuse may improve outcomes among patients with heart failure.