Latest from Medscape
Medscape
11 minutes ago
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- Medscape
Muscle Gains vs Heart Strain: A Deadly Trade-off?
Sudden cardiac deaths (SCDs) appear to be more frequent among men who practice bodybuilding, particularly those competing at high levels. A global study of more than 20,000 athletes is the first to report the incidence of sudden death in this population. As the author noted in the European Heart Journal , the aim was not to demonize bodybuilding but to promote safer practices. Bodybuilding focuses on increasing muscle mass and definition through physical exercise and a targeted diet. Unlike traditional sports, bodybuilding competitions evaluate the aesthetics of the body rather than athletic performance. Researchers identified 20,286 men who had competed in the International Fitness and Bodybuilding Federation (IFBB) events between 2005 and 2020. Using web-based searches, they determined which athletes died. Over a mean follow-up period of 8.1 ± 3.8 years, there were 121 deaths. Among the 99 cases with documented causes, 73 were sudden. The mean age at the time of death was 45 years. Of the 55 nontraumatic sudden deaths — excluding those from car accidents, suicide, or homicide — 46 were classified as SCDs. The overall incidence of deaths (sudden and nonsudden) was 63.61 per 100,000 person-years. Among active competitors, those who died within 1 year of their last IFBB event, the rate rose to 80.58. The incidence of SCDs was 24.18 in the entire cohort and 32.83 among competing athletes, who had a mean age of just 35 years at death. Professional bodybuilders had a fivefold higher risk for SCD than recreational bodybuilders (hazard ratio, 5.23 [3.58-7.64]). Available autopsies showed the presence of cardiomegaly and severe ventricular hypertrophy in 4 out of 5 cases. Risk Factors The study pointed to a broader issue in addition to bodybuilders, which could also affect nonprofessional athletes who practice strength training. What are the possible causes? Univadis Italy , a Medscape Network platform, asked Marco Vecchiato, MD, a specialist and researcher in the Sports and Exercise Medicine Division at the University of Padua, Padua, Italy, and the coordinator of the study. 'Our study had epidemiological purposes and was not designed to identify, in a cause-effect manner, the mechanisms underlying these premature deaths. However, the literature in the field has advanced some plausible hypotheses, suggesting that a combination of factors could contribute significantly to the increased risk,' said Vecchiato. These include: Intense training regimens, such as high-intensity workouts, place major strain on the cardiovascular (CV) and muscular systems. Extreme dietary practices, such as high protein intake and repeated weight cycling between off-season and on-season periods, can place significant stress on metabolic and CV systems. Dehydration techniques, such as rapid fluid loss before events using hydro-saline protocols or diuretics, can be dangerous. The use of doping substances, especially anabolic steroids and similar agents, can severely harm the CV, kidneys, liver, and nervous system. Doping Impact 'It is important to underline that, to date, there are no studies that have exclusively investigated the risk for death and SCD in a population of bodybuilders with the guarantee of not taking doping substances. However, recent evidence published in first-time journals and with long-term monitoring suggested a clear difference in terms of cumulative mortality between athletes with and without a history of anabolic steroid abuse,' said Vecchiato. He noted that performance-enhancing drug use is likely to be widespread at the highest competitive levels. In the US, where bodybuilding is more structured and athletes face intense competitive and aesthetic pressure with serious psychophysical consequences, many athletes speak openly about the use of performance-enhancing drugs. However, in Italy, 'The issue remains mostly hidden and is often not perceived as a medical risk but as 'a necessary means' to obtain a certain physique,' he said. Uncertain Rules Athletes are generally required to undergo regular medical checkups, but does the same apply to bodybuilders? 'In Italy, there are numerous bodybuilding federations, each with its own rules and requirements for membership. Some of these clearly state the obligation to present a competitive sports medical certificate, while others do not mention any specific medical requirements, thus allowing membership even in the absence of a health assessment. In these cases, the activity is not formally classified as a sport but rather as an activity for aesthetic purposes, which allows you to bypass some obligations required for competitive sports, including medical certification,' Vecchiato explained. Although not formally required by regulations, a sports center or gym may still ask a bodybuilder to provide a noncompetitive medical certificate, often for insurance purposes. Under Italian law, such certification is not mandatory for individuals engaging in noncompetitive physical activity unless they are affiliated with a national sports federation or a sports promotion body recognized by the Italian National Olympic Committee, which oversees organized sports and fitness initiatives in the country. 'This heterogeneous regulatory situation means that some athletes are subjected to in-depth sports medical check-ups annually, including a baseline electrocardiogram, stress test, spirometry, urine test, and any further investigations of a higher order, while others receive an evaluation with only an electrocardiogram in resting conditions. Finally, a nonnegligible portion of subjects may never be subjected to any structured medical evaluation, not even when starting or continuing the activity practiced,' he said. 'The first contact with a doctor can therefore only occur after the onset of advanced signs or symptoms, sometimes linked to already structured CV or metabolic damage, making any form of secondary prevention potentially late,' he said. These signs warrant cardiologic or psychological evaluation. 'The general practitioner can play a key role in recognizing warning signs (excessive muscle hypertrophy, extreme weight fluctuations, suspected use of illicit substances, marked and sudden mood changes in the absence of diagnosed mental illnesses, gynecomastia, extensive acne in adults not present during puberty, etc.) and directing them towards cardiological or psychological investigations,' warned Vecchiato. He also noted that 15% of SCDs in this population were traumatic. Obsessive body transformation goals, extreme practices, and substance misuse increase the risk for impulsive or self-harming behavior. This reinforces the need to prioritize the mental health of athletes. Vecchiato concluded that 'in addition to an intensified antidoping practice, the introduction of targeted CV screening and educational campaigns could significantly reduce the associated risks.' Raising awareness can encourage athletes to adopt safer training and nutrition programs and diets, to be supervised by a physician, and to refuse doping.
Medscape
an hour ago
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- Medscape
ACC Revises Obesity Control Strategies in Heart Failure
A new Scientific Statement from the American College of Cardiology (ACC) has named two anti-obesity drugs as options for symptom control in patients with heart failure. The benefit for these incretin mimics, semaglutide and tirzepatide, is attributed to symptom control, according to the statement. The document, published on June 13 in the Journal of the American College of Cardiology , states that each medication has the potential to reduce cardiovascular (CV) events related to heart failure, but neither has yet done so on the basis of level 1 evidence. The new recommendation appl ies only to heart failure with preserved ejection fraction (HFpEF). The safety and efficacy of these drugs has yet to be established for heart failure with reduced ejection fraction (HFrEF), according to the ACC statement. The new anti-obesity drugs were approved initially for type 2 diabetes. On the basis of substantial weight loss and their relative safety, the FDA subsequently granted indications for obesity alone in patients with at least one additional obesity-related comorbidity, such as hypertension, dyslipidemia, or obstructive sleep apnea. Current Indications for Incretin Mimetics Semaglutide has an indication for patients with CV disease, but not heart failure specifically, and obesity on the basis of the 2023 SELECT trial. Tirzepatide has an indication for patients with sleep apnea and obesity in the absence of diabetes on the basis of the 2024 SURMOUNT-OSA trial. In the 2023 STEP-HFpEF trial with semaglutide and the 2025 SUMMIT trial with tirzepatide, each agent was associated with a reduction in symptoms of heart failure in patients with HFpEF. However, the study designs and outcomes differed. For one, the HFpEF entry criterion was a left ventricular ejection fraction ≥ 45% in STEP-HFpEF but ≥ 50% in the SUMMIT trial. In dual primary endpoints, both included changes in the Kansas City Cardiomyopathy Questionnaire (KCCQ), but the first of the two trials evaluated weight change, while the second evaluated a composite endpoint of CV death and heart failure-related events. By listing semaglutide and tirzepatide as options within a comprehensive review of the treatment of obesity in heart failure, the new document steps in front of current regulatory guidance. In a table that juxtaposed FDA-approved indications for these drugs to evidence-based benefits as defined by the statement, only the latter identifies a role in heart failure. 'The intent of the Writing Committee in including this table was to highlight that there are no FDA-approved heart failure indications for the use of incretin-based anti-obesity medications to date,' said Michelle M. Kittleson, MD, PhD, director of Heart Failure Research at Cedars-Sinai Medical Center in Los Angeles, who chaired the committee. 'While clinicians might identify individuals with heart failure who meet the standard FDA-approved indications, it is important to also identify which of those patients also meet inclusion criteria for th e heart failure trials were benefit was shown,' Kittleson said. Semaglutide acts on the GLP-1 receptor alone. Tirzepatide is an agonist of both the GLP-1 receptor and glucose-dependent insulinotropic polypeptide. Both drugs are associated with strong signals of CV benefit overall and in heart failure specifically, even if the evidence in HFpEF is 'stronger,' according to the statement. Incretin drugs mimic hormones that downregulate appetite. They are considered third-generation anti-obesity agents on the basis of their targeted mechanism and a low relative risk for adverse events. More than a dozen such agents are now in various stages of development, according to the ACC statement. Semaglutide and Tirzepatide Trials Differ In the STEP-HFpEF trial, which like SUMMIT trial, was placebo controlled, the 7.8-point gain ( P <.0001) in the KCCQ on active therapy vs placebo was statistically significant, as was the percent body weight loss (-13.3% vs -2.6%; P < .001). The SUMMIT trial found a 6.9-point gain in the KCCQ score ( P < .001) relative to placebo, while the rate the composite event endpoint of CV death from events associated with heart failure was lower (9.9% vs 15.3%; P = .026), but CV deaths occurred in only 13 patients. Heart failure events were observed in 81 patients over 2 years of follow-up. In both studies, significant gains in the secondary endpoints of physical and exercise function were associated with the assigned weight-loss drug. On the evidence so far, the authors of the ACC statement concluded that despite the marginal benefit observed in the SUMMIT trial, no firm conclusions can be made about the ability of incretin therapies to protect patients with HFpEF against hard endpoints, Kittleson said. Until more data are available, she cautioned against the risk for 'indication creep,' the willingness to offer these drugs for potential benefits that have yet to be confirmed. Still, she added, 'the goal of the writing group was to strike a tone of cautious optimism guided by the available data.' Part of this optimism has been fueled by the 2023 SELECT trial, which enrolled more than 17,000 patients with overweight with CV disease but no diabetes. Relative to placebo, semaglutide was associated with a 20% reduction ( P < .001) in the composite primary endpoint of CV death, nonfatal myocardial infarction, and nonfatal stroke. Only 24% of patients in this study had heart failure, but the risk reduction in this group was consistent with that of the study population as a whole. Obesity is listed in most guidelines, including a 2024 ACC Expert Consensus Decision Pathway for Treatment of HFrEF, as a common comorbidity of heart failure and potentially treatable risk factor for symptoms and progression of the condition. However, the new statement differs from prior guidelines. Typically, lifestyle modifications are identified as a first step toward weight loss. 'Patients should not be required to try and fail lifestyle changes prior to initiating pharmacotherapy,' according to Olivia Gilbert, MD, a cardiologist specializing in advanced heart failure and transplantation at Atrium Wake Forest Baptist Medical Center, in Wake Forest, North Carolina. Although Gilbert was not part of the writing committee for the new document, she has been involved in developing clinical guidance statements for the ACC. The incretin therapies are more effective than lifestyle medications and safer than procedure-based weight-loss interventions, Gilbert said, providing a basis for suggesting they can be considered first line therapy for patients with symptomatic HFpEF. 'Lifestyle interventions should always be offered in conjunction with obesity medications,' she said.
Medscape
9 hours ago
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- Medscape
Injectable HIV Prevention Drug Gets FDA Nod
Individuals at risk for sexually acquired HIV have a new injectable option for preexposure prophylaxis (PrEP) with the US Food and Drug Administration's (FDA's) approval of lenacapavir, according to a press release from manufacturer, Gilead. Lenacapavir, marketed as Yeztugo, is the first twice-yearly injectable to be indicated for PrEP for adults and adolescents weighing at least 35 kg (approximately 77 lb). Lenacapavir is administered via an injection into the subcutaneous layer of fat in the abdomen. The resulting 'drug depot' may feel like a bump or nodule but resolves or shrinks before the next injection, according to the company. The approval was based on data from a pair of studies, PURPOSE 1 and PURPOSE 2. In the PURPOSE 1 study, published in The New England Journal of Medicine, lenacapavir was 100% effective in preventing HIV infection compared to background HIV incidence in cisgender women and significantly more effective than daily oral combination therapy of emtricitabine and tenofovir disoproxil fumarate (Truvada). Notably, the study included pregnant women and adolescents, and the drug was generally well tolerated. In the PURPOSE 2 study, also published in NEJM, lenacapavir was similarly effective for HIV infection prevention in a population of cisgender men and gender-diverse persons, with only two infections in the more than 2000 individuals randomized to lenacapavir. Overall, the injection was well tolerated but is contraindicated for individuals who test positive for HIV; a negative test is required before each injection, according to the company. The specifics of cost and insurance coverage for lenacapavir remain to be seen, but Gilead's Advancing Access medication assistance program will provide the drug at no cost to eligible patients, according to the press release. Lenacapavir was granted Breakthrough Therapy Designation by the FDA in October 2024 and was approved under the FDA's Priority Review process. Gilead has submitted a marketing authorization application with the European Medicines Agency and filed for regulatory approval in multiple countries worldwide including Australia, Brazil, Canada, and South Africa. The PURPOSE 1 and 2 studies were funded by Gilead.
Medscape
11 hours ago
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- Medscape
Early, Aggressive BP Lowering Tied to Better ICH Outcomes
Initiating intensive blood pressure (BP) lowering within a few hours of intracerebral hemorrhage (ICH) was associated with better neurologic outcomes, fewer serious adverse events, and better mortality compared to the more conservative standard treatment, new research confirmed. Best results were found when treatment was administered within 3 hours of ICH symptoms, a pooled analysis of the four Intensive BP Reduction in Acute Cerebral Hemorrhage Trials (INTERACT1-4) showed. While current guidelines set a target systolic BP of < 180 mm Hg within 1 hour of ICH symptom onset, the intensive treatment systolic target is < 140 Hg within 1 hour. The new findings were published online on June 18 in The Lancet Neurology . Timing Dependent? In addition to evaluating the safety and efficacy of early intensive treatment for ICH, the investigators also aimed to assess the impact of treatment timing. The INTERACT1-3 studies included 10,269 adults with acute ACH who presented within 6 hours of symptom onset and had a systolic BP of > 150 mm Hg. INTERACT4 included 1043 patients with suspected acute stroke who had a systolic BP of ≥ 150 mm Hg within 2 hours of symptom onset. In addition, 1029 study participants had a hemorrhagic form of stroke. All were randomly assigned to receive either intensive or guideline recommended BP-lowering treatment with locally available BP drugs within 1 hour. Scores on the modified Rankin scale were used to determine functional recovery, the primary outcome measure for the pooled analysis. Additionally, a CT substudy of nearly 3000 INTERACT participants was conducted to measure hematoma volume. Mean systolic BP rates at 1 hour were significantly lower for the intensive treatment group compared to the guideline group (149.6 mm Hg vs 158.8 mm Hg, respectively; P < .0001). Poor physical function, defined as a modified Rankin scale score of 3-6 at the end of follow-up, was significantly less likely after intensive BP lowering (odds ratio [OR], .85; P = .0001). The intensive group also had reduced odds of neurologic deterioration within 7 days compared to the guideline group (OR, .76; P = .0002), as well as lower odds of any serious adverse event (OR, .84; P = .0003) or death (OR, .83; P = .002). CT substudy results showed no significant effect on either relative or absolute hematoma growth in the first 24 hours from intensive vs guideline treatment. However, when intensive BP lowering was initiated within 3 hours of symptom onset, functional recovery was improved and hematoma growth was reduced in almost 25% of the patients with serial CT scans, investigators noted. Patients with mild-to-moderate severity, as measured by ICH scores, had even greater reductions in hematoma growth after early intensive BP-lowering treatment. The new pooled analysis of all four INTERACT trials confirms findings from INTERACT4, presented at the 2024 European Stroke Organization Conference Annual Meeting and reported by Medscape Medical News . 'Time Is Brain' In an accompanying editorial, David J. Werring, PhD, Department of Translational Neuroscience and Stroke, University College London Queen Square Institute of Neurology, London, noted that several previous studies showed no benefit of BP lowering in acute ischemic stroke, 'probably because acutely elevated blood pressure has a role in maintaining brain perfusion.' However, the pathophysiology of stroke from ICH 'is different, with a major role for hematoma expansion within the first few hours, a therapeutic target which might be reduced' by intensive BP lowering, he wrote. Still, Werring noted that possible benefits need to be weighed against possible risks; and he pointed out several study limitations, such as the low severity of ICH overall and the inclusion of INTERACT3 data, which may have introduced confounding from BP lowering being just one component of its treatment 'bundle,' alongside strict glucose control and anticoagulant reversal. 'Notwithstanding these important limitations, the data presented make a compelling case for ultra-early intensive blood pressure reduction as a potentially useful intervention to improve outcomes in people with acute ICH,' he wrote, adding that more research is needed. 'Meanwhile, the clear message from this meta-analysis is that earlier treatment is better, meaning that, once again, time is brain for patients with ICH,' Werring concluded.
Medscape
12 hours ago
- Health
- Medscape
Key Highlights in Ovarian Cancer From ASCO 2025
Novel drug combinations that improve outcomes, outstanding questions about treatment sequence, and encouraging results in chemotherapy resistant disease are among the ovarian cancer highlights presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting. Stephanie Gaillard, from Johns Hopkins School of Medicine, Baltimore, Maryland, begins with the ROSELLA trial of relacorilant plus nab-paclitaxel vs nab-paclitaxel alone in patients with platinum-resistant ovarian cancer. The results showed improved progression-free survival (PFS) and overall survival (OS) in this difficult-to-treat population. Next, she discusses the TRUST trial in advanced ovarian cancer, comparing radical upfront surgical therapy followed by chemotherapy with neoadjuvant chemotherapy followed by surgery, followed by further chemotherapy. Although PFS was improved by upfront surgery, OS was not, leaving the treatment sequence open to question. Dr Gaillard then reports on an updated survival analysis from the OVATION-2 study of intraperitoneal IMNN-001 plus neoadjuvant chemotherapy in newly diagnosed advanced epithelial ovarian cancer. The approach achieved impressive OS, alongside the previously reported PFS benefit. Finally, she reports on a phase 2 study of pembrolizumab and lenvatinib in recurrent or persistent clear cell ovarian carcinoma. The combination showed encouraging response rates and PFS in a population known to be highly resistant to chemotherapy.
