Lp(a) - an overlooked risk factor.

Lipoprotein(a) (Lp(a)) is an increasingly discussed and studied risk factor for atherosclerotic cardiovascular disease and aortic valve stenosis. Many genetic and epidemiological studies support the important causal role that Lp(a) plays in the incidence of cardiovascular disease. Although dependent upon the threshold and unit of measurement of Lp(a), most estimates suggest between 20 and 30% of the world's population have elevated serum levels of Lp(a). Lp(a) levels are predominantly mediated by genetics and are not significantly modified by lifestyle interventions. Efforts are ongoing to develop effective pharmacotherapies to lower Lp(a) and to determine if lowering Lp(a) with these medications ultimately decreases the incidence of adverse cardiovascular events. In this review, the genetics and pathophysiological properties of Lp(a) will be discussed as well as the epidemiological data demonstrating its impact on the incidence of cardiovascular disease. Recommendations for screening and how to currently approach patients with elevated Lp(a) are also noted. Finally, the spectrum of pharmacotherapies under development for Lp(a) lowering is detailed.

Association of pulse pressure with death, myocardial infarction, and stroke among cardiovascular outcome trial participants.

Background: Prior evidence demonstrates that pulse pressure (PP), a surrogate marker of arterial stiffness, is an independent risk factor for mortality and major adverse cardiovascular (CV) events. Objectives: The study aimed to identify the association of PP with death, myocardial infarction, and stroke among participants enrolled in large CV outcome clinical trials and determine if this association was impacted by pre-existing CV disease, or specific CV risk factors. Methods: A total of 65,382 individuals, ages 19 to 98 years, that were enrolled in one of five CV outcome trials were analyzed. Baseline demographics, history, blood pressures, and medications were collected. Univariate and multivariable analyses were conducted to explore temporal patterns, risks, and adjusted survival rates. Results: Mean baseline PP was 52 ± 12 mmHg. For every 10 mmHg increase in PP, there was an increased risk of death, stroke, or myocardial infarction (hazard ratio (HR) 1.11, 95 % CI 1.08 to 1.14, p < 0.001). Similarly, a PP ≥ 60 mmHg demonstrated an HR of 1.27 (95 % CI 1.19 to 1.36, p < 0.001) compared with PP < 60 mmHg. A similar association existed for all subgroups analyzed except for participants with a history of stroke where increasing PP did not increase risk (HR 1.02, 95 % CI 0.95 to 1.10, p = 0.53). PP was a better predictor of adverse outcomes when compared to both systolic and diastolic blood pressures using the AIC and C-index. Conclusions: Among participants enrolled in CV outcome trials, baseline PP is associated with increased risk of death, myocardial infarction, and stroke for those with pre-existing CV disease and risk factors with the exception of a prior history of stroke.

Aldosterone Synthase Inhibition With Lorundrostat for Uncontrolled Hypertension: The Target-HTN Randomized Clinical Trial.

Importance: Excess aldosterone production contributes to hypertension in both classical hyperaldosteronism and obesity-associated hypertension. Therapies that reduce aldosterone synthesis may lower blood pressure. Objective: To compare the safety and efficacy of lorundrostat, an aldosterone synthase inhibitor, with placebo, and characterize dose-dependent safety and efficacy to inform dose selection in future trials. Design, Setting, and Participants: Randomized, placebo-controlled, dose-ranging trial among adults with uncontrolled hypertension taking 2 or more antihypertensive medications. An initial cohort of 163 participants with suppressed plasma renin (plasma renin activity [PRA] ≤1.0 ng/mL/h) and elevated plasma aldosterone (≥1.0 ng/dL) were enrolled, with subsequent enrollment of 37 participants with PRA greater than 1.0 ng/mL/h. Interventions: Participants were randomized to placebo or 1 of 5 dosages of lorundrostat in the initial cohort (12.5 mg, 50 mg, or 100 mg once daily or 12.5 mg or 25 mg twice daily). In the second cohort, participants were randomized in a 1:6 ratio to placebo or lorundrostat, 100 mg once daily. Main Outcomes and Measures: The primary end point was change in automated office systolic blood pressure from baseline to study week 8. Results: Between July 2021 and June 2022, 200 participants were randomized, with final follow-up in September 2022. Following 8 weeks of treatment in participants with suppressed PRA, changes in office systolic blood pressure of -14.1, -13.2, -6.9, and -4.1 mm Hg were observed with 100 mg, 50 mg, and 12.5 mg once daily of lorundrostat and placebo, respectively. Observed reductions in systolic blood pressure in individuals receiving twice-daily doses of 25 mg and 12.5 mg of lorundrostat were -10.1 and -13.8 mm Hg, respectively. The least-squares mean difference between placebo and treatment in systolic blood pressure was -9.6 mm Hg (90% CI, -15.8 to -3.4 mm Hg; P = .01) for the 50-mg once-daily dose and -7.8 mm Hg (90% CI, -14.1 to -1.5 mm Hg; P = .04) for 100 mg daily. Among participants without suppressed PRA, 100 mg once daily of lorundrostat decreased systolic blood pressure by 11.4 mm Hg (SD, 2.5 mm Hg), which was similar to blood pressure reduction among participants with suppressed PRA receiving the same dose. Six participants had increases in serum potassium above 6.0 mmol/L that corrected with dose reduction or drug discontinuation. No instances of cortisol insufficiency occurred. Conclusions and Relevance: Among individuals with uncontrolled hypertension, use of lorundrostat was effective at lowering blood pressure compared with placebo, which will require further confirmatory studies. Trial Registration: ClinicalTrials.gov Identifier: NCT05001945.

Supplements for Lipid Lowering: What Does the Evidence Show?

PURPOSE: In this review, the regulation, proposed hypolipidemic mechanism, and efficacy of common dietary supplements (DSs) marketed for cardiovascular health are discussed. RECENT FINDINGS: Data demonstrate modest but inconsistent lipid-lowering effects with common DSs such as probiotics, soluble fibers, plant sterols, green tea, berberine, guggul, niacin, and garlic. Furthermore, data is limited regarding turmeric, hawthorn, and cinnamon. Red yeast rice has shown to be a beneficial DS, but its safety and efficacy are dependent upon its production quality and monacolin K content, respectively. Finally, soy proteins and omega-3 fatty acid-rich foods can have significant health benefits if used to displace other animal products as part of a healthier diet. Despite the rising use of DSs, data demonstrate unpredictable results. Patients should be educated on the difference between these DSs and evidence-based lipid-lowering medications proven to improve cardiovascular outcomes.

Newer alternatives for resistant hypertension: Beyond 2022 paradigms.

Given the increased incidence of resistant hypertension and no novel agents to manage hypertension for more than 15 years, there has been an increase in the development of newer agents with unique mechanisms that will hopefully aid in getting this subset of patients under control. More recent classes of agents include nonsteroidal mineralocorticoid receptor blockers, aminopeptidase A inhibitors, dual endothelin A and B antagonists and aldosterone synthetase inhibitors, and novel agents affecting angiotensinogen mRNA in the liver. All these agents are under different levels of development and, if all goes well, should be available to the public within the next 2-5 years. In addition to these agents, renal denervation is anticipated to be approved in the United States within the next 6-9 months, whereas it has already been authorized in certain European countries. Thus, by 2025 and later, we will have a more extensive armamentarium to help quell the rise in resistant hypertension. From early actuarial data associating elevated blood pressure with mortality to the first trials of blood pressure-lowering medications to contemporary American and European hypertension guidelines, the beneficial impact of blood pressure lowering in individuals with hypertension is well established1,2-4. Population-level decreases in incident cardiovascular disease and mortality over the past 50 years reflect this well-established impact. Yet, the year-over-year decline in the incidence of cardiovascular disease has now plateaued, and concomitantly rates of uncontrolled hypertension have increased5,6. Additionally, how the global COVID-19 pandemic impacts cardiovascular disease and hypertension-related outcomes is yet to be determined, but early data suggests population-level increases in blood pressure7.

National, regional, and urban-rural patterns in fixed-terrestrial broadband internet access and cardiac rehabilitation utilization in the United States.

Objective: Sparse patterns in fixed-terrestrial broadband internet access are predominantly observed among older adults and low income areas, which are interrelated factors also associated with low center-based cardiac rehabilitation (CR) utilization in the United States (US). Telehealth CR is proposed to increase CR utilization under an assumption that fixed-terrestrial broadband internet access is readily available nationwide and parallels CR utilization demand. We aimed to characterize national, geographical, and urban-rural patterns in fixed-terrestrial broadband internet access, CR eligibility rates, and center-based utilization throughout the US. Methods: Centers for Disease Control data were used to estimate CR eligibility rates and center-based utilization for 2017-2018 among Medicare fee-for-service beneficiaries aged ≥65 years. Census Bureau data for 2018 were used to estimate fixed-terrestrial broadband internet access among households of adults aged ≥65 years. Results: Southern states exhibited the highest percentage of households without broadband internet [median (IQR): 32% (24-39)] coupled with the highest CR eligibility rates [per 1,000 beneficiaries, median (IQR): 18 (15-21)] and lowest participation rates [percentage completing ≥1 session, median (IQR): 25% (17-33)]. Compared with urban areas, rural areas demonstrated significantly higher eligibility rates [15.5 (13.2-18.4) vs. 17.4 (14.5-21.0)], participation rates [30.6% (22.0-39.4) vs. 34.6% (22.6-48.3)], and percentage of households without broadband internet [23.8% (18.1-29.2) vs. 31.6% (26.5-37.6)], respectively. Conclusion: Overlapping patterns in fixed-terrestrial broadband internet access and CR eligibility rates and center-based utilization suggest telehealth CR policies need to account for the possibility that lack of broadband-quality internet access could be a barrier to accessing telehealth CR delivery models.

Geographical and Urban-Rural Disparities in Cardiac Rehabilitation Eligibility and Center-Based Use in the US.

This cross-sectional study analyzes county-level eligibility, participation, adherence, and completion rates for cardiac rehabilitation services among Medicare beneficiaries.

Comparative Effects of Low-Dose Rosuvastatin, Placebo, and Dietary Supplements on Lipids and Inflammatory Biomarkers.

BACKGROUND: Supplements are commonly used by individuals with indications for lipid-lowering therapy, but evidence of their effectiveness to lower low-density lipoprotein cholesterol (LDL-C) is lacking, particularly when compared with statins. OBJECTIVES: The trial objective was to compare the efficacy of a low-dose statin with placebo and 6 common supplements in impacting lipid and inflammatory biomarkers. METHODS: This was a single-center, prospective, randomized, single-blind clinical trial among adults with no history of atherosclerotic cardiovascular disease (ASCVD), an LDL-C of 70 to 189 mg/dL, and an increased 10-year risk of ASCVD. Participants were randomized to rosuvastatin 5 mg daily, placebo, fish oil, cinnamon, garlic, turmeric, plant sterols, or red yeast rice. The primary endpoint was the percent change in LDL-C from baseline for rosuvastatin 5 mg daily compared with placebo and each supplement after 28 days. The primary endpoint was evaluated in a hierarchical fashion with rosuvastatin first compared with placebo, then each supplement in a prespecified order using analysis of covariance. RESULTS: A total of 190 participants completed the study. The percent LDL-C reduction with rosuvastatin was greater than all supplements and placebo (P < 0.001). The difference in LDL-C reduction with rosuvastatin compared with placebo was -35.2% (95% CI: -41.3% to -29.1%; P < 0.001). None of the dietary supplements demonstrated a significant decrease in LDL-C compared with placebo. Adverse event rates were similar across study groups. CONCLUSIONS: Among individuals with increased 10-year risk for ASCVD, rosuvastatin 5 mg daily lowered LDL-C significantly more than placebo, fish oil, cinnamon, garlic, turmeric, plant sterols, and red yeast rice. (Supplements, Placebo, or Rosuvastatin Study [SPORT]; NCT04846231).

Individualized exercise prescription and cardiac rehabilitation following a spontaneous coronary artery dissection or aortic dissection.

Aims: Prescribed aerobic-based exercise training is a low-risk fundamental component of cardiac rehabilitation (CR). Secondary prevention therapeutic strategies following a spontaneous coronary artery dissection (SCAD) or aortic dissection (AD) should include CR. Current exercise guidance for post-dissection patients recommends fundamental training components including target heart rate zones are not warranted. Omitting fundamental elements from exercise prescriptions risks safety and makes it challenging for both clinicians and patients to understand and implement recommendations in real-world practice. We review the principles of exercise prescription for CR, focusing on translating guidelines and evidence from well-studied high-risk CR populations to support the recommendation that exercise testing and individualized exercise prescription are important for patients following a dissection. Methods and results: When patients self-perceive exercise intensity there is a tendency to underestimate intensities within metabolic domains that should be strictly avoided during routine exercise training following a dissection. However, exercise testing associated with CR enrolment has gained support and has not been linked to adverse events in optimally medicated post-dissection patients. Graded heart rate and blood pressure responses recorded throughout exercise testing provide key information for developing an exercise prescription. An exercise prescription that is reflective of medical history, medications, and cardiorespiratory fitness optimizes patient safety and yields improvements in blood pressure control and cardiorespiratory fitness, among other benefits. Conclusion: This clinical practice and education article demonstrates how to develop and manage a CR exercise prescription for post-acute dissection patients that can be safe and effective for maintaining blood pressure control and improving cardiorespiratory fitness pre-post CR.

Effects of Finerenone, a Novel Nonsteroidal Mineralocorticoid Receptor Antagonist, on Cardiovascular Disease, Chronic Kidney Disease, and Blood Pressure.

PURPOSE OF REVIEW: Finerenone, an FDA-approved nonsteroidal mineralocorticoid receptor (MR) antagonist, has been evaluated in context of chronic kidney disease (CKD) and associated cardiovascular disease (CVD). In this review, we summarize pre-clinical and clinical studies focused on the impact of finerenone on these disease processes. RECENT FINDINGS: Activation of the MR upregulates genes encoding for facilitators of tissue damage. Finerenone binding to a helix domain in this receptor inhibits receptor function. Studies in murine models of kidney disease, heart failure, hypertension, and vascular injury demonstrate significant protective effects of finerenone against further disease progression, as well as association with reduced oxidative stress, inflammation, and fibrosis. Phase 1-3 clinical trials with finerenone show safety and efficacy in improving renal and cardiovascular outcomes in patients with CKD. Research thus far encourages the addition of finerenone to the standard of care for certain CKD patients, especially those especially at risk for or with pre-existing cardiovascular disease. Continued study of the effect of finerenone in diverse patient populations and different disease states is needed.

The obesity paradox in heart failure: What is the role of cardiorespiratory fitness?

The obesity paradox describes a survival benefit for higher body mass index in patients with heart failure. But other factors like cardiorespiratory fitness may play a role in heart failure development, severity, and survival. Although more research is needed to better understand the relationships between body mass index and fitness in patients with heart failure, evidence indicates that recommending weight loss and an exercise program is appropriate for most patients.