Effect of Empagliflozin on Heart Failure Outcomes After Acute Myocardial Infarction
Empagliflozin reduced the risk of HF in patients with left ventricular dysfunction or congestion after acute myocardial infarction.
Summary
Insights From the EMPACT-MI Trial
[Posted 21/May/2024]
AUDIENCE: Cardiology, Emergency Medicine
KEY FINDINGS: Empagliflozin reduced the risk of HF in patients with left ventricular dysfunction or congestion after acute myocardial infarction.
BACKGROUND: Empagliflozin reduces the risk of heart failure (HF) events in patients with type 2 diabetes at high cardiovascular risk, chronic kidney disease, or prevalent HF irrespective of ejection fraction. Whereas the EMPACT-MI trial (Effect of Empagliflozin on Hospitalization for Heart Failure and Mortality in Patients With Acute Myocardial Infarction) showed that empagliflozin does not reduce the risk of the composite of hospitalization for HF and all-cause death, the effect of empagliflozin on first and recurrent HF events after myocardial infarction is unknown.
DETAILS: EMPACT-MI was a double-blind, randomized, placebo-controlled, event-driven trial that randomized 6522 patients hospitalized for acute myocardial infarction at risk for HF on the basis of newly developed left ventricular ejection fraction of 45% or signs or symptoms of congestion to receive empagliflozin 10 mg daily or placebo within 14 days of admission. In prespecified secondary analyses, treatment groups were analyzed for HF outcomes. Over a median follow-up of 17.9 months, the risk for first HF hospitalization and total HF hospitalizations was significantly lower in the empagliflozin compared with the placebo group (118 [3.6%] versus 153 [4.7%] patients with events; hazard ratio, 0.77 [95% CI, 0.60, 0.98]; P=0.031, for first HF hospitalization; 148 versus 207 events; rate ratio, 0.67 [95% CI, 0.51, 0.89]; P=0.006, for total HF hospitalizations). Subgroup analysis showed consistency of empagliflozin benefit across clinically relevant patient subgroups for first and total HF hospitalizations. The need for new use of diuretics, renin-angiotensin modulators, or mineralocorticoid receptor antagonists after discharge was less in patients randomized to empagliflozin versus placebo (all P<0.05).
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Source: Hernandez, A. F., Udell, J. A., Jones, W. S., et al. (2024). Effect of Empagliflozin on Heart Failure Outcomes After Acute Myocardial Infarction: Insights From the EMPACT-MI Trial. XXXXX. 2024; 149: 1627-1638. Published: May, 2024. DOI: 10.1161/CIRCULATIONAHA.124.069217.
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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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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