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Prospective Cohort: Combined CRP, LDL Cholesterol, and Lipoprotein(a) Levels Predict 30-Year Cardiovascular Risk in Women

8 Dec, 2024 | 20:58h | UTC

Background: Current 10-year risk models do not fully capture lifetime cardiovascular disease (CVD) risk. Inflammation, low-density lipoprotein (LDL) cholesterol, and lipoprotein(a) are distinct pathways associated with atherosclerosis. While their value in predicting 5- to 10-year cardiovascular risk is established, data on their combined long-term predictive utility, particularly over three decades in women, are limited.

Objective: To determine whether a single baseline measurement of high-sensitivity C-reactive protein (CRP), LDL cholesterol, and lipoprotein(a) provides additive and independent predictive value for 30-year cardiovascular outcomes in initially healthy women.

Methods: This prospective cohort study included 27,939 initially healthy U.S. women (mean age, 54.7 years) from the Women’s Health Study, enrolled between 1992 and 1995. Baseline levels of high-sensitivity CRP, LDL cholesterol, and lipoprotein(a) were measured. Participants were followed for 30 years for a first major adverse cardiovascular event (myocardial infarction, coronary revascularization, stroke, or cardiovascular death). Adjusted hazard ratios (HRs) for each biomarker’s quintiles were estimated, as well as combined models including all three biomarkers simultaneously.

Results: Over 30 years, 3,662 first major cardiovascular events occurred. Higher baseline quintiles of CRP, LDL cholesterol, and lipoprotein(a) were each associated with elevated 30-year risk. Compared to the lowest quintile, adjusted HRs for the top quintile were 1.70 (95% CI, 1.52–1.90) for CRP, 1.36 (95% CI, 1.23–1.52) for LDL cholesterol, and 1.33 (95% CI, 1.21–1.47) for lipoprotein(a). Each marker contributed independently, and models incorporating all three showed the greatest risk discrimination. Participants with all three biomarkers in the highest quintile had a HR of 2.63 (95% CI, 2.16–3.19) for the primary endpoint.

Conclusions: A single combined baseline assessment of high-sensitivity CRP, LDL cholesterol, and lipoprotein(a) strongly predicted CVD events over 30 years. These findings suggest extending beyond traditional 10-year estimates to identify long-term risk, reinforcing the need for early prevention strategies addressing multiple biological pathways.

Implications for Practice: Measuring these three biomarkers early may inform more personalized, prolonged preventive efforts. While lowering LDL cholesterol remains foundational, addressing inflammation and lipoprotein(a) could further optimize long-term CVD prevention. Nonetheless, caution is advised before embracing new interventions lacking robust long-term data.

Study Strengths and Limitations: Strengths include the extended 30-year follow-up, a large, well-characterized cohort, and standardized biomarker assessments. Limitations include a predominantly White, female population, limiting generalizability. Single-time-point biomarker measurements and evolving statin use over time add complexity. Despite these constraints, the study underscores the multifactorial nature of long-term CVD risk.

Future Research: Further investigations should evaluate targeted interventions on inflammation and lipoprotein(a), potentially through long-term clinical trials and more diverse populations. Such research could clarify the benefits of a multimodal risk-reduction strategy.

Reference: Ridker PM, Moorthy MV, Cook NR, Rifai N, Lee I-M, Buring JE. Inflammation, Cholesterol, Lipoprotein(a), and 30-Year Cardiovascular Outcomes in Women. N Engl J Med 2024;391:2087-2097. DOI: http://doi.org/10.1056/NEJMoa2405182

 


Phase 2 RCT: Zerlasiran Lowers Lipoprotein(a) Levels by Over 80% in Patients With ASCVD

24 Nov, 2024 | 20:18h | UTC

Background: Elevated lipoprotein(a) [Lp(a)] is a genetically determined risk factor for atherosclerotic cardiovascular disease (ASCVD) and aortic stenosis. Traditional lipid-lowering therapies, including statins and lifestyle modifications, do not effectively reduce Lp(a) levels. Small-interfering RNA (siRNA) therapies targeting hepatic production of apolipoprotein(a) offer a potential approach to lowering Lp(a) concentrations.

Objective: To evaluate the efficacy and safety of zerlasiran, an siRNA targeting apolipoprotein(a) synthesis, in reducing serum Lp(a) concentrations in patients with ASCVD.

Methods: In this randomized, double-blind, placebo-controlled phase 2 trial, 178 adults with stable ASCVD and elevated Lp(a) levels (≥125 nmol/L) were enrolled across 26 sites in Europe and South Africa. Participants were randomized to receive subcutaneous zerlasiran at doses of 450 mg every 24 weeks (n=45), 300 mg every 16 weeks (n=42), or 300 mg every 24 weeks (n=44), or matching placebo every 16 weeks (n=23) or every 24 weeks (n=24). The primary outcome was the time-averaged percent change in Lp(a) concentration from baseline to week 36.

Results: Zerlasiran significantly reduced Lp(a) levels compared to placebo. The placebo-adjusted time-averaged percent reductions were −85.6% (95% CI, −90.9% to −80.3%) for 450 mg every 24 weeks, −82.8% (95% CI, −88.2% to −77.4%) for 300 mg every 16 weeks, and −81.3% (95% CI, −86.7% to −76.0%) for 300 mg every 24 weeks. Median percent reductions at week 36 exceeded 90% in all zerlasiran groups. The most common adverse events were mild injection site reactions, occurring in up to 7.1% of participants. No serious adverse events were attributed to the study drug.

Conclusions: Zerlasiran was well-tolerated and produced substantial reductions in Lp(a) levels over 36 weeks in patients with ASCVD.

Implications for Practice: If validated in larger, long-term studies that assess cardiovascular outcomes, zerlasiran may offer a novel treatment for patients with elevated Lp(a), addressing a significant unmet need in cardiovascular risk management. Clinicians should, however, exercise caution until the impact on hard endpoints such as myocardial infarction and stroke, as well as long-term safety, are confirmed.

Study Strengths and Limitations: Strengths include the randomized, double-blind design and significant Lp(a) reductions observed. Limitations involve the predominantly White, male study population, limiting generalizability. The study did not assess clinical endpoints like cardiovascular events, so the impact on actual cardiovascular risk remains unknown. Additionally, the moderate sample size and duration may not detect rare adverse events or long-term effects, necessitating further investigation.

Future Research: Larger, long-term phase 3 trials are needed to confirm these findings, assess the impact on cardiovascular events, and evaluate efficacy and safety in more diverse populations.

Reference: Nissen SE, Wang Q, Nicholls SJ, et al. Zerlasiran—A Small-Interfering RNA Targeting Lipoprotein(a): A Phase 2 Randomized Clinical Trial. Journal of the American Medical Association. Published online November 18, 2024. DOI: http://doi.org/10.1001/jama.2024.21957

 


Meta-analysis: Low/Moderate-Intensity Statins with Ezetimibe May Offer Better LDL-C Reduction and Safety over High-Intensity Statins

24 Nov, 2024 | 20:01h | UTC

Background: Despite widespread use of high-intensity statin therapy, achieving target LDL-C levels and reducing cardiovascular events remain challenging in patients with or at high risk of atherosclerotic cardiovascular disease (ASCVD). High-intensity statins can have dose-dependent adverse effects, limiting their tolerability. Combining low/moderate-intensity statins with ezetimibe, a cholesterol absorption inhibitor, may enhance lipid-lowering efficacy with fewer side effects.

Objective: To compare the clinical effectiveness and safety of low/moderate-intensity statins combined with ezetimibe versus high-intensity statin monotherapy in reducing major adverse cardiovascular events (MACEs) and lowering LDL-C levels.

Methods: A systematic review and meta-analysis were conducted according to PRISMA guidelines. Fifteen studies (6 randomized controlled trials [RCTs] and 9 observational studies) encompassing 251,450 participants were included. The primary outcome was a composite of cardiovascular death or major cardiovascular events. Secondary outcomes included lipid-lowering efficacy and safety measures such as muscle-related adverse events and liver enzyme elevations.

Results: Observational studies indicated that combination therapy was associated with lower rates of the primary composite outcome (HR = 0.76; 95% CI [0.73, 0.80]), cardiovascular death (HR = 0.80; 95% CI [0.74, 0.88]), all-cause death (HR = 0.84; 95% CI [0.78, 0.91]), and non-fatal stroke (HR = 0.81; 95% CI [0.75, 0.87]). RCTs showed that combination therapy resulted in a greater number of patients achieving LDL-C levels < 70 mg/dL (RR = 1.27; 95% CI [1.21, 1.34]) and significant reductions in LDL-C (MD = –7.95 mg/dL; 95% CI [–10.02, –5.89]) and total cholesterol (MD = –26.77 mg/dL; 95% CI [–27.64, –25.89]). Combination therapy also reduced muscle-related adverse events (RR = 0.52; 95% CI [0.32, 0.85]) and liver enzyme elevations (RR = 0.51; 95% CI [0.29, 0.89]) in RCTs.

Conclusions: Combining low/moderate-intensity statins with ezetimibe may offer superior lipid-lowering effects and better safety profiles compared to high-intensity statin monotherapy. While observational studies suggest improved clinical outcomes, these findings need confirmation from large-scale, long-term RCTs.

Implications for Practice: The combination therapy could be a viable option for patients intolerant to high-intensity statins or those requiring additional LDL-C lowering to reach target levels. However, clinicians should interpret these potential benefits cautiously due to reliance on observational data for clinical outcomes and the lack of robust RCT evidence.

Study Strengths and Limitations: Strengths include a comprehensive search strategy and a large patient population. Limitations involve heavy reliance on observational studies for clinical outcomes.

Future Research: Large, well-designed RCTs with longer follow-up periods are needed to confirm the clinical benefits and safety of the combination therapy over high-intensity statin monotherapy across diverse populations.

Reference: Sydhom P, et al. The clinical effectiveness and safety of low/moderate-intensity statins & ezetimibe combination therapy vs. high-intensity statin monotherapy: a systematic review and meta-analysis. BMC Cardiovascular Disorders. 2024; DOI: https://doi.org/10.1186/s12872-024-04144-y

 


Phase 2 RCT: Oral Muvalaplin Significantly Reduces Lipoprotein(a) Levels in High-Risk Patients

20 Nov, 2024 | 14:22h | UTC

Background: Elevated lipoprotein(a) [Lp(a)] levels are an independent risk factor for atherosclerotic cardiovascular disease and calcific aortic valve stenosis. Current therapeutic options to lower Lp(a) are limited, and no approved pharmacotherapies specifically target Lp(a) reduction.

Objective: To evaluate the efficacy and safety of muvalaplin, an oral small-molecule inhibitor of Lp(a) formation, in reducing Lp(a) levels in patients at high risk of cardiovascular events.

Methods: In this phase 2, randomized, double-blind, placebo-controlled trial, 233 adults aged 40 years or older with Lp(a) concentrations of 175 nmol/L or greater and high cardiovascular risk (due to atherosclerotic cardiovascular disease, diabetes, or familial hypercholesterolemia) were enrolled across 43 sites worldwide. Participants were randomized to receive muvalaplin at doses of 10 mg/d (n = 34), 60 mg/d (n = 64), or 240 mg/d (n = 68), or placebo (n = 67) for 12 weeks. The primary endpoint was the placebo-adjusted percentage change from baseline in Lp(a) levels at week 12, measured using both an intact Lp(a) assay and a traditional apolipoprotein(a)-based assay.

Results

At week 12, muvalaplin achieved significant, dose-dependent reductions in Lp(a) levels compared with placebo. Using the intact Lp(a) assay, placebo-adjusted reductions were:

  • 47.6% (95% CI, 35.1%-57.7%) for 10 mg/d
  • 81.7% (95% CI, 78.1%-84.6%) for 60 mg/d
  • 85.8% (95% CI, 83.1%-88.0%) for 240 mg/d

Using the apolipoprotein(a)-based assay, reductions were:

  • 40.4% (95% CI, 28.3%-50.5%) for 10 mg/d
  • 70.0% (95% CI, 65.0%-74.2%) for 60 mg/d
  • 68.9% (95% CI, 63.8%-73.3%) for 240 mg/d

Dose-dependent decreases in apolipoprotein B levels were also observed, with placebo-adjusted reductions ranging from 8.9% to 16.1%. Muvalaplin was well tolerated across all doses, with no significant safety or tolerability concerns reported.

Conclusions: Muvalaplin significantly reduced Lp(a) levels in high-risk patients over a 12-week period and was well tolerated. These findings suggest that muvalaplin could be an effective oral therapy for lowering Lp(a) levels.

Implications for Practice: Muvalaplin may offer a convenient oral option to reduce elevated Lp(a) levels, potentially lowering cardiovascular risk in high-risk patient populations.

Study Strengths and Limitations: Strengths of the study include its randomized, double-blind, placebo-controlled design and the use of both traditional and novel assays to accurately measure Lp(a) levels. Limitations involve the short duration of the trial, the relatively small sample size for each dosage group, and the lack of assessment of long-term cardiovascular outcomes and safety.

Future Research: Long-term studies are necessary to determine whether the reduction in Lp(a) levels with muvalaplin translates into decreased cardiovascular events. Future research should also explore optimal dosing strategies and assess the long-term safety profile of muvalaplin.

Reference: Nicholls SJ, Ni W, Rhodes GM, et al. Oral Muvalaplin for Lowering of Lipoprotein(a): A Randomized Clinical Trial. JAMA. Published online November 18, 2024. DOI: http://doi.org/10.1001/jama.2024.24017

 


RCT: Lipoprotein(a) and LDL-C as Independent Cardiovascular Risk Factors in Statin Trials

5 Nov, 2024 | 17:50h | UTC

Background: Low-density lipoprotein cholesterol (LDL-C) and lipoprotein(a) [Lp(a)] are both known risk factors for atherosclerotic cardiovascular disease (ASCVD). However, the interaction between Lp(a) and LDL-C levels in relation to ASCVD risk, especially in the context of LDL-C-lowering treatments like statins, remains unclear. This study aimed to clarify if LDL-C reduction impacts Lp(a)-associated ASCVD risk.

Objective: This meta-analysis examined whether LDL-C reduction with statins affects ASCVD risk mediated by elevated Lp(a) levels.

Methods: Data from 27,658 participants across six statin trials were analyzed, including both placebo and statin groups. ASCVD risk was assessed using multivariable Cox proportional hazards models with adjustments for various cardiovascular risk factors. The study evaluated continuous associations between Lp(a) levels, LDL-C levels, and ASCVD risk.

Results: Elevated Lp(a) levels were associated with higher ASCVD risk across all LDL-C levels, even among patients with the lowest LDL-C achieved through statin therapy. Statin-treated patients with Lp(a) >50 mg/dL exhibited a significantly higher ASCVD risk, even in the lowest quartile of achieved LDL-C (HR 1.38, 95% CI 1.06–1.79). The highest risk was observed in individuals with both elevated Lp(a) and LDL-C levels (HR 1.90, 95% CI 1.46–2.48).

Conclusions: Lp(a) and LDL-C are independent risk factors for ASCVD, with LDL-C lowering alone insufficient to mitigate the risk associated with elevated Lp(a).

Implications for Practice: These findings underscore the need for distinct strategies to manage patients with elevated Lp(a), particularly as LDL-C reduction alone does not fully address the associated ASCVD risk.

Study Strengths and Limitations: This study’s strength lies in its large participant pool and robust statistical analysis; however, variability in Lp(a) measurement methods across trials may limit precision.

Future Research: Investigations into therapies specifically targeting Lp(a) may offer additional ASCVD risk reduction beyond LDL-C lowering alone.

Reference: Bhatia HS, et al. Independence of Lipoprotein(a) and Low-Density Lipoprotein Cholesterol–Mediated Cardiovascular Risk: A Participant-Level Meta-Analysis. Circulation. 2024;150:00–00. DOI: http://doi.org/10.1161/CIRCULATIONAHA.124.069556

 


Meta-Analysis: Long-Term Low-Carbohydrate Diets Improve Dyslipidemia but Not Glycemic Control in Type 2 Diabetes – J Diabetes Investig

17 Aug, 2024 | 19:14h | UTC

Study Design and Population: This systematic review and meta-analysis examined the impact of long-term low-carbohydrate diets (LCD) on glycemic control and other metabolic parameters in adults with type 2 diabetes. Six randomized controlled trials (RCTs) involving 524 participants were included, with intervention durations ranging from 12 to 24 months.

Main Findings: The meta-analysis found no significant difference in glycated hemoglobin (HbA1c) levels between participants on long-term LCD and those on control diets (SMD -0.11, 95% CI -0.33 to 0.11, P = 0.32). Similarly, there were no significant differences in weight loss, blood pressure, or low-density lipoprotein (LDL) cholesterol levels. However, LCDs were associated with a significant increase in high-density lipoprotein (HDL) cholesterol (SMD 0.22, 95% CI 0.04 to 0.41, P = 0.02) and a decrease in triglyceride levels (SMD -0.19; 95% CI -0.37 to -0.02; P = 0.03).

Implications for Practice: While long-term LCDs do not appear to improve glycemic control in individuals with type 2 diabetes, they may be beneficial for managing dyslipidemia, specifically by increasing HDL cholesterol and reducing triglycerides. These findings suggest that LCDs could be considered as part of a strategy for addressing cardiovascular risk factors in this population, but they should not be relied upon for glycemic management.

Reference: Ichikawa, T., Okada, H., Hironaka, J., Nakajima, H., Okamura, T., Majima, S., … & Fukui, M. (2024). Efficacy of long‐term low carbohydrate diets for patients with type 2 diabetes: A systematic review and meta‐analysis. Journal of Diabetes Investigation. https://doi.org/10.1111/jdi.14271.

 


Consensus Recommendations: Cardiovascular Risks in People With Narcolepsy – J Am Hear Assoc

10 Aug, 2024 | 21:48h | UTC

Introduction: The Journal of the American Heart Association recently published a consensus guideline by a panel of sleep and cardiology experts to address the heightened cardiovascular risks in individuals with narcolepsy. Given the increased prevalence of hypertension and cardiometabolic comorbidities in this population, the panel developed recommendations aimed at mitigating these risks.

Key Points:

1 – Increased Cardiovascular Risk in Narcolepsy:

– Individuals with narcolepsy, both Type 1 (NT1) and Type 2 (NT2), exhibit higher rates of cardiovascular and cardiometabolic diseases, such as hypertension, obesity, and diabetes, compared to the general population.

– The association of narcolepsy with conditions like obstructive sleep apnea (OSA) and restless legs syndrome further elevates cardiovascular risk.

2 – Monitoring and Early Detection:

– Clinicians should annually monitor blood pressure, weight, and waist circumference in patients with narcolepsy, even in the absence of existing cardiovascular disease.

– Screening for lipid levels and hemoglobin A1c is recommended, especially in patients with risk factors like hypertension, obesity, and diabetes.

3 – Lifestyle and Therapeutic Interventions:

– Patients should be educated about the link between narcolepsy and cardiovascular disease. Emphasis should be placed on maintaining optimal sleep duration, regular exercise, healthy eating, and reducing sodium intake.

– The American Heart Association’s “Life’s Essential 8” guidelines should be followed to enhance overall cardiovascular health.

4 – Medication Management:

– Narcolepsy medications, particularly stimulants and sodium oxybate, can increase cardiovascular risk. Clinicians should consider the patient’s cardiovascular profile when prescribing these treatments and explore alternatives with lower cardiovascular impact if necessary.

5 – Sodium Reduction:

– High sodium intake, from both diet and certain narcolepsy medications, is associated with increased blood pressure and cardiovascular disease. Patients should be advised to reduce sodium intake, and clinicians should consider prescribing lower-sodium alternatives when possible.

Conclusion: These expert consensus recommendations underscore the importance of proactive cardiovascular risk management in patients with narcolepsy. By implementing these guidelines, clinicians can help mitigate the long-term cardiovascular risks associated with this chronic sleep disorder.

Guideline Reference: Kwon Y, Gami AS, Javaheri S, et al. Cardiovascular Risks in People With Narcolepsy: Expert Panel Consensus Recommendations. Journal of the American Heart Association. 2024;13. DOI: 10.1161/JAHA.124.035168. Available at: https://doi.org/10.1161/JAHA.124.035168.

 


RCT: No benefit of Apolipoprotein A1 infusions in preventing cardiovascular events post-myocardial infarction

29 Apr, 2024 | 12:42h | UTC

This international, double-blind, placebo-controlled trial investigated the effect of apolipoprotein A1 (CSL112) infusions on cardiovascular outcomes in patients with recent acute myocardial infarction and multivessel coronary disease. A total of 18,219 patients were randomized to receive either four weekly 6 g infusions of CSL112 or a placebo within five days of initial medical contact. Over 90, 180, and 365 days, the trial found no significant difference in the risk of myocardial infarction, stroke, or cardiovascular death between the two groups. Additionally, adverse events were similar across groups, though hypersensitivity was more common in the CSL112 group.

 

Reference (link to abstract – $ for full-text):

Michael Gibson et al. (2024). Apolipoprotein A1 Infusions and Cardiovascular Outcomes after Acute Myocardial Infarction. New England Journal of Medicine. DOI: 10.1056/NEJMoa2400969.

 


Cohort Study: Metabolic biomarkers and long-term risk of psychiatric disorders in over 200,000 individuals

27 Apr, 2024 | 18:29h | UTC

Study Design and Population:

This population-based cohort study assessed 211,200 participants from the Apolipoprotein-Related Mortality Risk (AMORIS) cohort, who underwent occupational health screening primarily in the Stockholm region of Sweden from 1985 to 1996. Participants were followed longitudinally, with statistical analysis performed between 2022 and 2023. The study included extensive biomarker measurements such as glucose, triglycerides, and high-density lipoprotein.

 

Main Findings:

The study found significant associations between certain metabolic biomarkers and the risk of developing psychiatric disorders such as depression, anxiety, and stress-related disorders. Specifically, high levels of glucose (HR, 1.30) and triglycerides (HR, 1.15) were linked to an increased risk of these disorders, while high levels of high-density lipoprotein (HR, 0.88) were associated with a reduced risk. These findings held true across both genders and all disorders tested, with nested case-control analyses confirming these trends.

 

Implications for Practice:

The study suggests that metabolic dysregulation, as indicated by specific biomarkers, may either increase the risk or be a marker of increased risk for the development of common psychiatric disorders. These findings support the potential for closer monitoring and follow-up of individuals with abnormal metabolic profiles to aid in the prevention and early diagnosis of psychiatric conditions.

 

Reference (free full-text):

Chourpiliadis, C. et al. (2024). Metabolic Profile and Long-Term Risk of Depression, Anxiety, and Stress-Related Disorders. JAMA Network Open, 7(4), e244525. DOI: 10.1001/jamanetworkopen.2024.4525


M-A Proportional increase in new-onset diabetes with different intensities of statin therapy

27 Apr, 2024 | 15:41h | UTC

Study Design and Population:

This research is a meta-analysis of individual participant data from large, long-term, randomized, double-blind controlled trials involving statins. The study encompasses 19 trials comparing statin use to placebo and four trials comparing varying intensities of statin therapy, involving a total of 154,664 participants over periods ranging from 4.3 to 4.9 years. Participants were adults enrolled in statin trials with a scheduled duration of at least two years and a participant count of at least 1000.

 

Main Findings:

The study revealed a dose-dependent increase in the incidence of new-onset diabetes when using statins. Participants receiving low to moderate-intensity statin therapy showed a 10% increase in new-onset diabetes annually compared to placebo, while those on high-intensity statin therapy exhibited a 36% increase. The absolute increases in new-onset diabetes were significantly influenced by the extent of HbA1c measurement. Notably, a large portion of new-onset diabetes cases occurred among participants with baseline glycaemic levels nearing the diabetes diagnostic threshold. Furthermore, the study found a moderate rise in mean glucose levels and HbA1c among those without baseline diabetes, and a significant worsening of glycemia among those with existing diabetes.

 

Implications for Practice:

The findings highlight a moderate, dose-dependent risk of new-onset diabetes associated with statin therapy, especially in individuals close to the diagnostic threshold for diabetes. These results should be considered in the clinical management of statin therapy, balancing the small increases in glycemia against the substantial benefits of statins in reducing cardiovascular risk. Healthcare providers should monitor glycaemic control in patients on statin therapy, particularly those prescribed high-intensity doses.

 

Reference (free full-text):

Cholesterol Treatment Trialists’ (CTT) Collaboration. (2024). Effects of statin therapy on diagnoses of new-onset diabetes and worsening glycaemia in large-scale randomised blinded statin trials: an individual participant data meta-analysis. Lancet Diabetes & Endocrinology, (Online First), 1-12. DOI: https://doi.org/10.1016/S2213-8587(24)00040-8


Pragmatic Cluster-Randomised Trial: Efficacy of a Fixed-Dose Polypill in Reducing Cardiovascular Disease Risk in Rural Iran

21 Apr, 2024 | 21:05h | UTC

Study Design and Population: The PolyPars Study was structured as a two-arm pragmatic cluster-randomised trial within the larger PARS cohort study. It targeted residents aged over 50 in a district in southern Iran, dividing 91 villages into two groups: one receiving a once-daily polypill (containing two antihypertensives, a statin, and aspirin) alongside non-pharmacological interventions, and the other receiving only the non-pharmacological interventions. The trial included 4,415 participants aged 50-75 years, with the primary endpoint being the first occurrence of major cardiovascular events.

Main Findings: Over a median follow-up of 4.6 years, adherence to the polypill was high at 86%. The intervention arm showed a significant reduction in the incidence of the primary outcome, with only 4.0% (88 participants) experiencing major cardiovascular events compared to 8.0% (176 participants) in the control arm. This translates to a hazard ratio of 0.50, indicating a 50% reduction in risk, and an absolute risk reduction of 4.0%.

Implications for Practice: The study demonstrates the significant potential of fixed-dose combination therapy with the polypill to halve the risk of major cardiovascular diseases in a population-level intervention. This finding supports the polypill as a safe and effective strategy for both primary and secondary prevention of cardiovascular diseases, particularly in settings where access to individual medications and consistent medical supervision might be limited.

Reference: Fatemeh Malekzadeh et al. (2024). Effectiveness of polypill for primary and secondary prevention of cardiovascular disease: a pragmatic cluster-randomised controlled trial (PolyPars). Heart, heartjnl-2023-323614. DOI: 10.1136/heartjnl-2023-323614.


Genetic analysis reveals Lipoprotein(a) is significantly more atherogenic than LDL on a per-particle basis

20 Mar, 2024 | 19:24h | UTC

Study Design and Population: This study utilized genome-wide association studies (GWAS) within the UK Biobank population to examine the atherogenicity of lipoprotein(a) (Lp(a)) compared to low-density lipoprotein (LDL), focusing on their apolipoprotein B (apoB) content. The researchers identified two clusters of single nucleotide polymorphisms (SNPs) associated with mass concentrations of Lp(a) and LDL, comprising 107 and 143 variants, respectively. The sample included subjects from the UK Biobank, allowing for a broad and genetically diverse analysis.

Main Findings: The study’s Mendelian randomization approach found that a 50 nmol/L increase in Lp(a)-apoB was associated with a 1.28 times higher odds ratio (OR) for coronary heart disease (CHD) compared to a 1.04 times increase for the same increment in LDL-apoB. Furthermore, a comparison using polygenic scores demonstrated that the hazard ratio (HR) for CHD per 50 nmol/L increase in apoB was significantly higher for the Lp(a) cluster (1.47) than for the LDL cluster (1.04), suggesting that Lp(a) is approximately 6.6 times more atherogenic than LDL on a per-particle basis.

Implications for Practice: These findings highlight the substantial atherogenic potential of Lp(a) compared to LDL, indicating that Lp(a) should be a key focus for drug intervention strategies in populations at risk for CHD. The marked difference in atherogenicity underscores the importance of targeted treatments and monitoring for individuals with elevated Lp(a) levels.

Reference: Björnson, E., Adiels, M., Taskinen, M.-R., Burgess, S., Chapman, M. J., Packard, C. J., & Borén, J. (2024). Lipoprotein(a) Is Markedly More Atherogenic Than LDL: An Apolipoprotein B-Based Genetic Analysis. Journal of the American College of Cardiology, 83(3), 385-395. DOI: https://doi.org/10.1016/j.jacc.2023.10.039. Access the study here: Link


Observational Study | More data suggesting Rosuvastatin 10mg/Ezetimibe 10mg combo may be an alternative to Rosuvastatin 20mg

31 Jul, 2023 | 14:38h | UTC

Combination Lipid-Lowering Therapy in Patients Undergoing Percutaneous Coronary Intervention – Journal of the American College of Cardiology (link to abstract – $ for full-text)

Commentaries:

Statins post PCI: Moderate intensity plus ezetimibe may be preferable – Cardiology News

Combination Lipid-Lowering Therapy After PCI – American College of Cardiology

Related: Open-label RCT | Moderate-intensity statin plus ezetimibe is noninferior to high-intensity statin monotherapy in patients with atherosclerotic cardiovascular disease.

 

Commentary on Twitter

 


RCT | Pitavastatin effective in the primary prevention of cardiovascular disease in HIV-infected individuals

26 Jul, 2023 | 13:35h | UTC

Pitavastatin to Prevent Cardiovascular Disease in HIV Infection – New England Journal of Medicine (link to abstract – $ for full-text)

Commentaries:

Pitavastatin lowers risk of cardiovascular events in people living with HIV – Aidsmap

Statins reduce cardiovascular risk in people living with HIV, new global study finds – STAT

Pitavastatin Cuts MACE in HIV-Infected Patients: REPRIEVE – TCTMD

 

Commentary on Twitter

 


M-A | Vegetarian diets may modestly improve cardiometabolic profile in high-risk individuals

26 Jul, 2023 | 13:15h | UTC

Vegetarian Dietary Patterns and Cardiometabolic Risk in People With or at High Risk of Cardiovascular Disease: A Systematic Review and Meta-analysis – JAMA Network Open

Commentary: M-A: Vegetarian diets may modestly improve cardiometabolic profile in high-risk individuals – HCP Live

 


USPSTF Statement | Evidence lacking for lipid disorders screening in asymptomatic children and adolescents

20 Jul, 2023 | 11:13h | UTC

Screening for Lipid Disorders in Children and Adolescents: US Preventive Services Task Force Recommendation Statement – JAMA

Evidence Report: Screening for Lipid Disorders in Children and Adolescents: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force – JAMA

Editorial: Still “on the Fence” About Universal Childhood Lipid Screening: The USPSTF Reaffirms an I Statement – JAMA

Patient Page: Screening for Lipid Disorders in Children and Adolescents – JAMA

Commentary: USPSTF: Screening Kids for Lipid Disorders Still Needs More Data – TCTMD

 


Secondary analysis of a RCT | Bempedoic acid reduces CV events in statin-intolerant patients with high CV risk

26 Jun, 2023 | 00:49h | UTC

Summary: This secondary analysis of a Randomized Clinical Trial (RCT) evaluated the efficacy of bempedoic acid in primary prevention of cardiovascular events among statin-intolerant patients at high cardiovascular risk. From a total of 13,970 participants, 4206 met the criteria for primary prevention and were analyzed in this study. Those allocated to receive bempedoic acid showed a significant reduction in major cardiovascular events, reflected in a hazard ratio of 0.70.

The average age of this patient cohort was 68 years, and most participants (66%) were diagnosed with diabetes. Treatment with bempedoic acid also led to a significant 21.3% reduction in low-density lipoprotein cholesterol (LDL-C) levels and a 21.5% decrease in high-sensitivity C-reactive protein levels, suggesting improved cardiovascular health.

This study underscores the potential benefits of lipid-modulating therapy for primary prevention in high-risk patients, who are often undertreated. However, it is important to note the inherent limitations of this secondary analysis. The analysis was performed on a subgroup within a larger clinical trial, which could potentially lead to false-positive findings due to multiple testing. Furthermore, the results may not generalize to younger populations, those with lower pretreatment LDL-C levels, those without diabetes, or those with a lower baseline cardiovascular risk.

Article: Bempedoic Acid for Primary Prevention of Cardiovascular Events in Statin-Intolerant Patients – JAMA (free for a limited period)

Editorial: Bempedoic Acid for High-Risk Primary Prevention of Cardiovascular Disease: Not a Statin Substitute but a Good Plan B – JAMA (free for a limited period)

See also: Visual Abstract

Commentary: Study Suggests Bempedoic Acid Could Find Role in Primary Prevention – HCP Live

Original Study: RCT | Bempedoic acid shows modest reduction in cardiovascular events for statin-intolerant patients

 


M-A | Plant-based diets reduce key atherogenic lipoproteins

30 May, 2023 | 11:48h | UTC

Vegetarian or vegan diets and blood lipids: a meta-analysis of randomized trials – European Heart Journal

Editorial: Plant-based dietary patterns and atherogenic lipoproteins – European Heart Journal

 


RCT | Statins do not prevent early cardiac dysfunction in anthracycline-treated cancer patients

15 May, 2023 | 13:07h | UTC

Statins to prevent early cardiac dysfunction in cancer patients at increased cardiotoxicity risk receiving anthracyclines – European Heart Journal – Cardiovascular Pharmacotherapy (link to abstract – $ for full-text)

 

Commentary on Twitter

 


Consensus Statement | Homozygous Familial Hypercholesterolemia: new treatments and clinical guidance

5 May, 2023 | 14:58h | UTC

2023 Update on European Atherosclerosis Society Consensus Statement on Homozygous Familial Hypercholesterolaemia: new treatments and clinical guidance – European Heart Journal

 


M-A | Mediterranean & low-fat diets may reduce mortality and non-fatal MI in patients with high cardiovascular risk

3 Apr, 2023 | 13:59h | UTC

Summary: This systematic review and network meta-analysis aimed to determine the relative efficacy of different diets for preventing mortality and major cardiovascular events in patients at increased risk of cardiovascular disease. The study identified 40 randomized trials with 35,548 participants across seven dietary programs.

Moderate certainty evidence showed that Mediterranean and low-fat diets, with or without physical activity or other interventions, reduced all-cause mortality and non-fatal myocardial infarction in patients with increased cardiovascular risk. Mediterranean diet programs were also likely to reduce stroke risk.

Other dietary programs generally were not superior to minimal intervention. When compared with one another, no convincing evidence was found that the Mediterranean diet was superior to the low-fat diets in preventing mortality or non-fatal myocardial infarction.

Article: Comparison of seven popular structured dietary programmes and risk of mortality and major cardiovascular events in patients at increased cardiovascular risk: systematic review and network meta-analysis – The BMJ

News Release: Benefits of Mediterranean and low fat diet programmes in patients at risk of cardiovascular disease – BMJ Newsroom

Commentary: Mediterranean, Low-Fat Diets Both Good for Health: Network Meta-analysis – TCTMD

 


M-A | Effects of statin therapy on glycemic control and insulin resistance

31 Mar, 2023 | 13:45h | UTC

Effects of statin therapy on glycemic control and insulin resistance: A systematic review and meta-analysis – European Journal of Pharmacology

Related:

Cohort study: Statin therapy initiation linked to increased risk of diabetes progression.

Meta-Analysis: Medications that Reduce or Increase the Risk of New Onset Diabetes

Observational Study Points to an Increased Risk of Diabetes Among Patients Using Statins

Another Observational Study Showing Association of Statin Use with Risk of New‐Onset Diabetes Mellitus

Cohort Study: Statin Use Associated with a 38% Higher Risk of Incident Type 2 Diabetes

 


Coffee consumption vs. caffeine avoidance: cardiac ectopy, daily steps, and sleep impacts

27 Mar, 2023 | 13:32h | UTC

Summary: A prospective, randomized, case-crossover trial studied the acute health effects of caffeinated coffee consumption in 100 ambulatory adults.

Participants were monitored using continuous electrocardiogram devices, wrist-mounted accelerometers, and ongoing glucose monitoring systems for 14 days. They received daily text messages instructing them to either consume caffeinated coffee or abstain from caffeine.

The primary outcome was the mean number of daily premature atrial contractions. Results indicated that caffeinated coffee consumption didn’t lead to significantly more daily premature atrial contractions compared to caffeine avoidance. However, it was associated with a higher number of daily premature ventricular contractions, increased daily steps, and reduced nightly sleep.

Article: Acute Effects of Coffee Consumption on Health among Ambulatory Adults – New England Journal of Medicine (link to abstract – $ for full-text)

Commentaries:

What to know about new research on coffee and heart risks – Associated Press

CRAVE Trials Offers Most Comprehensive Overview Yet of Impact of Coffee, Caffeine Intake – HCP Live

Acute Effects of Coffee Consumption on Health – American College of Cardiology

 


Dissecting coffee’s impact: high consumption lowers blood pressure, raises LDL-cholesterol

27 Mar, 2023 | 13:25h | UTC

Coffee consumption and associations with blood pressure, LDL-cholesterol and echocardiographic measures in the general population – Scientific Reports

 


M-A | Effects of dairy intake on markers of cardio-metabolic health in adults

23 Mar, 2023 | 12:35h | UTC

Effects of dairy intake on markers of cardio-metabolic health in adults – a systematic review with network meta-analysis – Advances in Nutrition

 

Commentary on Twitter

 


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