FDA Approves Drug for Heart Disorder Caused by Transthyretin-Mediated Amyloidosis
FDA approved Attruby (acoramidis) to treat adults with cardiomyopathy (disorder that affects heart muscle) of wild-type or variant (hereditary) transthyretin-mediated amyloidosis (ATTR-CM) to reduce death and hospitalization related to heart problems.
ACTION: The U.S. Food and Drug Administration has approved Attruby (acoramidis) to treat adults with cardiomyopathy (disorder that affects heart muscle) of wild-type or variant (hereditary) transthyretin-mediated amyloidosis (ATTR-CM) to reduce death and hospitalization related to heart problems.
Attruby is taken orally, twice daily. Recommended dosing is available in the prescribing information.
DISEASE OR CONDITION: ATTR-CM is a rare and serious disease that affects the heart muscle. In patients with ATTR-CM, there is a build-up of protein deposits in the heart, causing the walls of the heart to become stiff, and making the left ventricle unable to properly relax and fill with blood (called cardiomyopathy). As the condition progresses, the heart can become unable to pump blood out adequately, causing heart failure.
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There are two types of ATTR-CM, hereditary ATTR-CM (hATTR-CM) and wild-type ATTR-CM (wATTR-CM). In hATTR-CM, which can run in families, there’s a variant in the transthyretin gene, which results in protein deposits in the heart. In wATTR-CM, there is no variant in the transthyretin gene.
While the true prevalence of ATTR-CM is unknown, increasing awareness and enhanced diagnostic tools have led to increasing estimates of the number of patients with ATTR-CM.
EFFECTIVENESS: The efficacy and safety of Attruby were evaluated in a multicenter, international, randomized, double-blind, placebo-controlled study in 611 adult patients with wild-type or hereditary (variant) ATTR-CM (NCT03860935).
The primary endpoint of the study included all-cause mortality and cumulative frequency of cardiovascular-related hospitalizations (CVH) over 30 months. At 30 months, more patients taking Attruby vs placebo were alive (81% vs 74%) and there were fewer CVH in those taking Attruby vs placebo (mean number of 0.3 vs 0.6 per year).
SAFETY INFORMATION: The most common adverse reactions were diarrhea and upper abdominal pain. Most of these gastrointestinal adverse reactions were categorized as mild and resolved without drug discontinuation.
DESIGNATIONS: Attruby received orphan drug designation for this indication.
Source: FDA Approves Drug for Heart Disorder Caused by Transthyretin-Mediated Amyloidosis. FDA. Published: November 25, 2024.
Re-envisioning the Lifespan Approach to Cardiovascular Disease Prevention and Treatment in Women
The anticipated life course of women supports a broadening focus on CVD toward that of lifelong care and emphasize key transitional stages for women - early risk factor onset, pregnancy, menopausal transition, and so on. This review is a call to action to re-envision a health system approach for lifespan prevention, detection, and treatment pathways to reduce CVD risk in women.
KEY FINDINGS:
- Mortality: CVD deaths in women exceed combined deaths from breast and lung diseases.
- Gap in Care: Insufficient sex-specific evidence continues to hinder lifesaving care.
- Call to Action: Transition from episodic care to a lifelong cardiovascular health system for women.
BACKGROUND: Despite the common misconception that respiratory or oncological diseases pose the greatest threat to women, Cardiovascular Disease (CVD) accounts for more female deaths than breast cancer, lung cancer, and chronic lung disease combined, with a comparable mortality to that of men. Historically, both the public and the medical community have underestimated CVD risks in women, leading to diagnostic delays and a scarcity of sex-specific evidence to guide clinical interventions. While advances have been made in the diagnosis, treatment and outcomes of CVD in women, there often remains insufficient evidence to guide effective, lifesaving care of women.
DETAILS: This review of sex-specific and traditional CVD risk and risk-enhancing factors in women identifies areas of knowledge gaps to consider for investigation. A focus on the coronary vasculature reveals physiological differences of clinical relevance which can be interrogated. Inspection of and addressing disadvantage and gender bias in both the medical and lay communities should continue to be addressed. As CVD results from traditional risk factors and emerging risk-enhancing factors, a focus on the detection of preclinical cardiovascular disease may be of particular importance for women. Unique risk markers originate early in pre-menopausal women, as this is considered a healthy period of life. Awareness and implementation of the existing knowledge of sex-specific risk factors and sex-specific thresholds to educate women and physicians are needed. The anticipated life course of women supports a broadening focus on CVD toward that of lifelong care and emphasize key transitional stages for women-early risk factor onset, pregnancy, menopausal transition, and so on. This review is a call to action to re-envision a health system approach for lifespan prevention, detection, and treatment pathways to reduce CVD risk in women.
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Kidney Juxtaglomerular Cells' Renin Shutdown Mechanism in Blood Pressure Regulation
Juxtaglomerular cells monitor calcium levels to toggle renin release. Studying live tissue outperforms isolated cell models for understanding renin regulation. Targeting renin suppression could yield novel hypertension therapies and reduce related complications.
KEY FINDINGS: The findings demonstrate that juxtaglomerular cells shut down renin production through calcium-mediated mechanisms observed directly in kidney tissue. This approach highlights the brakes on hormone systems, differing from traditional focus on activation pathways.
BACKGROUND: Juxtaglomerular cells in the kidney serve as key sensors for blood pressure homeostasis. These cells release renin, a hormone that elevates blood pressure when levels drop too low. They rely on intracellular calcium as an on-off switch to control renin production, preventing hypotension.
DETAILS: Juxtaglomerular cells function as the body's primary baroreceptors, constantly assessing systemic blood pressure through mechanosensory mechanisms in the afferent arterioles. When pressure falls, these cells detect reduced stretch and rising intracellular calcium, triggering renin release to activate the renin-angiotensin-aldosterone system (RAAS). This study shifts focus to the inhibitory phase: how elevated calcium levels or other signals in intact kidney tissue suppress renin synthesis, acting as a regulatory "brake" to prevent overactivation. Traditional research emphasized renin induction using isolated cell cultures, which overlooked tissue-specific interactions like interstitial signaling and vascular coupling. By contrast, this work analyzed living kidney slices, revealing precise calcium-dependent shutdown pathways that halt transcription and secretion in real-time. This tissue-level insight explains why excessive renin persists in hypertension, potentially due to faulty off-switches, and opens avenues for therapies targeting suppression rather than blockade alone—such as modulating calcium channels or downstream inhibitors.
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Fish-Oil Supplementation and Cardiovascular Events in Patients Receiving Hemodialysis
In this trial involving participants receiving hemodialysis, fish oil (n-3 fatty acids) was compared with corn-oil placebo. The rate of serious cardiovascular events was lower with daily fish-oil supplementation.
KEY FINDINGS: The rate of serious cardiovascular events among participants receiving maintenance hemodialysis was lower with daily supplementation with n-3 fatty acids than with placebo.
BACKGROUND: Cardiovascular disease is the leading cause of death in patients receiving hemodialysis, yet effective preventive therapies remain limited. Supplementation with n-3 polyunsaturated fatty acids, especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), may have cardiovascular benefits in the general population, but efficacy among patients receiving hemodialysis is uncertain.
DETAILS: In a double-blind, randomized, placebo-controlled trial conducted at 26 sites in Canada and Australia, we assigned adult patients receiving maintenance hemodialysis to daily supplementation with fish oil (4 g of n-3 polyunsaturated fatty acids [1.6 g of EPA and 0.8 g of DHA]) or corn-oil placebo. The primary end point was a composite of all serious cardiovascular events including sudden and nonsudden cardiac death, fatal and nonfatal myocardial infarction, peripheral vascular disease leading to amputation, and fatal and nonfatal stroke. Secondary end points included extension of the primary end point to include noncardiac causes of death, the individual components of the primary end point, and a first cardiovascular event or death from any cause. In a double-blind, randomized, placebo-controlled trial conducted at 26 sites in Canada and Australia, we assigned adult patients receiving maintenance hemodialysis to daily supplementation with fish oil (4 g of n-3 polyunsaturated fatty acids [1.6 g of EPA and 0.8 g of DHA]) or corn-oil placebo. The primary end point was a composite of all serious cardiovascular events including sudden and nonsudden cardiac death, fatal and nonfatal myocardial infarction, peripheral vascular disease leading to amputation, and fatal and nonfatal stroke. Secondary end points included extension of the primary end point to include noncardiac causes of death, the individual components of the primary end point, and a first cardiovascular event or death from any cause.
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Copyright © Massachusetts Medical Society. All rights reserved.
Source: Lok, C. E., Farkouh, M., Hemmelgam, B. R., et al. Fish-Oil Supplementation and Cardiovascular Events in Patients Receiving Hemodialysis. NEJM. 2025; Published: November 7, 2025. DOI: 10.1056/NEJMoa2513032.
Prenatal PM2.5 Exposure Induces Offspring Hypertension via Nrf2/NLRP3 Pathway
Overall, prenatal fine particulate matter exposure induces excessive inflammation and oxidative stress in paraventricular nucleus microglia through the Nrf2/NLRP3 signaling pathway, resulting in central and peripheral sympathetic overactivation, leading to hypertension and left ventricular hypertrophy.
KEY FINDINGS: Overall, prenatal fine particulate matter exposure induces excessive inflammation and oxidative stress in paraventricular nucleus microglia through the Nrf2/NLRP3 signaling pathway, resulting in central and peripheral sympathetic overactivation, leading to hypertension and left ventricular hypertrophy.
BACKGROUND: Adverse factors during pregnancy can significantly increase the incidence of hypertension in adult offspring. Activation of the sympathetic nervous system is closely associated with the development and progression of hypertension.
DETAILS: Authors established a model of offspring hypertension induced by prenatal fine particulate matter exposure to evaluate the role of the sympathetic nervous system activation. Quantitative immunofluorescence and Western blot analysis were used to assess the levels of activated and inhibitory sympathetic neurons. The effects of the central and peripheral sympathetic nervous systems were evaluated using clonidine and renal sympathetic denervation. In addition, the activation of microglia in the lateral ventricle region and the expression of the Nrf2 (nuclear factor E2-related factor)/ NLRP3 (NLR family pyrin domain-containing 3) signaling pathway were analyzed. The adult offspring showed increased neuronal hyperactivity and sympathetic nervous system activity. Specific inhibition of the central sympathetic nervous system and renal denervation effectively reversed the prenatal fine particulate matter-induced blood pressure elevation in adult offspring. In addition, overactivation of oxidative stress and microglia-mediated inflammation in the paraventricular nucleus was responsible for increased central sympathetic activity in the adult offspring exposed to prenatal fine particulate matter. Furthermore, authors confirmed the critical role of the Nrf2/NLRP3 signaling pathway in oxidative stress and inflammation activation in the paraventricular nucleus of adult offspring.
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Copyright © American Heart Association, Inc. All rights reserved.
Source: Zhang, X., Yang, B., Li, M., et al. Prenatal PM2.5 Exposure Induces Offspring c via Nrf2/NLRP3 Pathway. Hypertension. 2025; 82(11): 1841-1843), Published: November, 2025. DOI: 10.1161/HYPERTENSIONAHA.125.2487.
Oxidized High-Density Lipoprotein Associates with Cardiometabolic Dysfunction in Coronary Artery Disease and Acute Coronary Syndrome
Oxidized HDL levels are highest in patients with ACS. Patients with stable CAD have higher levels than healthy controls. Correspondingly, the parameters of HDL function measured in this study, which all indicate a loss of HDL's atheroprotective function, correlate with these findings. Our study establishes a novel mechanistic pathway linking oxidized HDL to the presence of an ACS.
KEY FINDINGS: HDLLox levels are highest in patients with ACS. Patients with stable CAD have higher levels than healthy controls. Correspondingly, the parameters of HDL function measured in this study, which all indicate a loss of HDL's atheroprotective function, correlate with these findings. Our study establishes a novel mechanistic pathway linking oxidized HDL to the presence of an ACS.
BACKGROUND: High-density lipoprotein (HDL) function, rather than its concentration, plays a crucial role in the development of coronary artery disease (CAD). Diminished HDL antioxidant properties, indicated by elevated oxidized HDL (nHDLLox) and diminished paraoxonase-1 (PON-1) activity, may contribute to vascular dysfunction and inflammation. Data on these associations in CAD patients, including acute coronary syndrome (ACS), remain limited. The aim of this study is to assess the association of oxidized HDL with PON-1 activity, oxidized low-density lipoprotein (LDL), vascular cell adhesion molecule-1 (VCAM-1), IL-6 levels, and nitric oxide (NO) production as markers of vascular health.
DETAILS: Authors assessed HDL function in three groups: 90 CAD patients, 90 healthy controls, and 90 ACS patients. HDL antioxidant function was measured using a validated biochemical assay to quantify oxidized HDL (nHDLox). Plasma PON-1 activity, oxidized LDL, VCAM-1, IL-6, and NO production were also evaluated. ACS patients had nHDLLox levels 140% higher than healthy controls (p < 0.001). Higher nHDLox levels were significantly linked to vascular inflammation, reflected by elevated VCAM-1 levels. Additionally, a reduced PON-1 activity indicates an impaired antioxidant protection in ACS patients. Finally, oxidized LDL levels were elevated, and NO production was reduced, suggesting impaired vascular function.
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Copyright © John Wiley & Sons, Inc. All rights reserved
Source: Sasko, B., Pagonas, N., Christ, M., et al. Oxidized High-Density Lipoprotein Associates with Cardiometabolic Dysfunction in Coronary Artery Disease and Acute Coronary Syndrome. Journal of Internal Medicine. 2025; 298(5): 464-477. Published: November, 2025. DOI: 10.1111/joim.70019.
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