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Reframing Aspirin’s Role in Primary Prevention: Evolving evidence has refined our understanding of aspirin’s role in primary prevention. While earlier trials established cardiovascular benefits, more recent data emphasize the importance of patient selection to optimise outcomes. A 2019 meta-analysis (N=164,225) showed aspirin reduced serious vascular events by 12% and non-fatal MI by ~20%, with a manageable rise in major bleeding [HR 1.43; NNH 210] (1); the Antithrombotic Trialists’ Collaboration echoed that absolute benefits in primary prevention, though smaller than in secondary prevention, remain clinically relevant in high-risk individuals, especially those with diabetes or multiple cardiovascular risk factors. (2)

This evolution is reflected in current guidelines. The USPSTF (United States Preventive Services Task Force, 2022) recommends individualized use of aspirin in adults aged 40–59 years with a ≥10% 10-year CVD risk. The ESC (European Society of Cardiology, 2021) suggests aspirin for patients with diabetes who are at high or very high cardiovascular risk and have no contraindications. The ACC/AHA (American College of Cardiology/American Heart Association, 2019) supports aspirin use in adults aged 40–70 years who are at high ASCVD risk and have a low risk of bleeding. Together, these guidelines support a risk-based approach, where judicious aspirin use offers preventive value in selected individuals. (3)

India’s Premature CVD Burden Requires a Different Lens: Indians develop CVD nearly a decade earlier than Western populations, with the age of developing MI being 53 years in Indians compared to 58 years in Western countries. (4) Premature deaths account for 62% of CVD mortality, and one-third of acute coronary syndrome cases occur before age 50. Despite this burden, less than half of patients with hypertension and diabetes are treated, and only ~20% achieve control. (5) Conventional 10-year risk scores often underestimate risk in younger Indians, making lifetime risk tools likely more appropriate. Genetic predisposition, inflammatory states, thin-fat phenotype, and poor cardiometabolic risk factor control heighten ASCVD risk, supporting earlier, more aggressive prevention, including aspirin when indicated. (4)

Lifetime Risk Depends on Classic Modifiable Factors: A pooled analysis by the Global Cardiovascular Risk Consortium (2025) highlighted the long-term impact of five key risk factors—cardio-metabolic (hypertension, diabetes, dyslipidemia), partially modifiable (smoking), and metabolic lifestyle-related (abnormal BMI)—which together account for ~50% of global CVD burden. At age 50, individuals with all five had a lifetime CVD risk of 38% in men and 24% in women, while those without gained 10–13 additional CVD-free years. Midlife modification of blood pressure and smoking provided the greatest gains in both CVD-free and overall survival, indicating the importance of early, integrated risk factor control for primary prevention. (6) In India, control of cardio-metabolic risk is poor, with only ~7% of T2D patients meeting targets for glucose, BP, and lipids, (7) and over 50% of newly diagnosed cases are overweight or obese, highlighting the need for aggressive CVD prevention. (8)

Individualized Use: CV Risk, Age, and Bleeding Must Guide: In primary prevention, the net clinical benefit of aspirin lies in carefully balancing ischemic versus bleeding risk. Risk scores often overlook enhancers such as kidney disease, family history, elevated Lp(a), or low socioeconomic status. (3) In individuals with elevated Lp(a ≥50 mg/dL), aspirin was linked to a 52% lower risk of ASCVD mortality (HR 0.48), supporting a precision-guided approach. For high-risk patients with low bleeding risk, accurate risk stratification is key to identifying when aspirin adds true preventive value with minimal harm. Clinical tools such as the Aspirin-Guide app support personalised decision-making for initiating aspirin for CV event prevention. (9)

Case Profile: High-Risk, Low-Bleed– A Candidate for Aspirin: A 55-year-old hypertensive, sedentary male with a family history of premature CHD. BMI: 26 kg/m²; systolic BP: 150 mmHg; total cholesterol: 220 mg/dL; HDL: 40 mg/dL. He is a non-smoker, non-diabetic, with no history of GI bleeding, peptic ulcer disease, or NSAID/steroid use.

His profile includes cardio-metabolic risk factors (hypertension, elevated LDL-C), a non-modifiable risk (family history of ASCVD), and a metabolic lifestyle-linked factor (BMI). He qualifies as high CV risk with low bleeding risk, where aspirin offers likely net benefit, per DCRM 2.0 (Diabetes, Cardiorenal, and Metabolic Diseases) 2024 guidelines recommending low-dose aspirin (75–100 mg/day) in such patients with ≥2 major risk factors.

Final Message: Low-dose aspirin for primary prevention is appropriate in individuals with elevated ASCVD risk and low bleeding risk. Current guidelines and risk assessment tools support a selective, individualised approach. When initiated in the right patient profile, aspirin can help reduce the incidence of primary cardiovascular events.

References:

1. Zheng, Sean L, and Alistair J Roddick. “Association of Aspirin Use for Primary Prevention With Cardiovascular Events and Bleeding Events: A Systematic Review and Meta-analysis.” JAMA vol. 321,3 (2019): 277-287. doi:10.1001/jama.2018.20578

2. Antithrombotic Trialists’ (ATT) Collaboration et al. “Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials.” Lancet (London, England) vol. 373,9678 (2009): 1849-60. doi:10.1016/S0140-6736(09)60503-1

3. Della Bona, Roberta et al. “Aspirin in Primary Prevention: Looking for Those Who Enjoy It.” Journal of clinical medicine vol. 13,14 4148. 16 Jul. 2024, doi:10.3390/jcm13144148

4. Puri, Raman et al. “Lipid Association of India 2023 update on cardiovascular risk assessment and lipid management in Indian patients: Consensus statement IV.” Journal of clinical lipidology vol. 18,3 (2024): e351-e373. doi:10.1016/j.jacl.2024.01.006

5. Kalra, Ankur et al. “The burgeoning cardiovascular disease epidemic in Indians – perspectives on contextual factors and potential solutions.” The Lancet regional health. Southeast Asia vol. 12 100156. 10 Feb. 2023, doi:10.1016/j.lansea.2023.100156

6. Global Cardiovascular Risk Consortium et al. “Global Effect of Cardiovascular Risk Factors on Lifetime Estimates.” The New England journal of medicine, 10.1056/NEJMoa2415879. 30 Mar. 2025, doi:10.1056/NEJMoa2415879

7. Anjana, Ranjit Mohan et al. “Metabolic non-communicable disease health report of India: the ICMR-INDIAB national cross-sectional study (ICMR-INDIAB-17).” The lancet. Diabetes & endocrinology vol. 11,7 (2023): 474-489. doi:10.1016/S2213-8587(23)00119-5

8. Dalal, N., Patel, D., Chaturvedi, A., & Shah, A. (2022). Real-world observational study to capture demographic details of newly diagnosed type 2 diabetes mellitus. International Journal of Research in Medical Sciences, 10(10), 2251–2256. https://doi.org/10.18203/2320-6012.ijrms20222375

9. Razavi, Alexander C et al. “Aspirin use for primary prevention among US adults with and without elevated Lipoprotein(a).” American journal of preventive cardiology vol. 18 100674. 27 Apr. 2024, doi:10.1016/j.ajpc.2024.100674

10. Handelsman, Yehuda et al. “DCRM 2.0: Multispecialty practice recommendations for the management of diabetes, cardiorenal, and metabolic diseases.” Metabolism: clinical and experimental vol. 159 (2024): 155931. doi:10.1016/j.metabol.2024.155931

According to a new study published in JAMA ,calprotectin may serve as a mechanistically informed biomarker for atherosclerotic cardiovascular disease (ASCVD), independent of established risk factors and biomarkers. However its clinical utility requires further investigation. This study was conducted by Yu Zuo and fellow researchers.

Patients suffering from long COVID may exhibit persistent inflammation in the heart and lungs for up to a year following SARS-CoV-2 infection-even when standard medical tests return normal results-potentially placing them at elevated risk for future cardiac and pulmonary conditions. These findings come from a new study conducted by researchers at the Icahn School of Medicine at Mount Sinai and published in the Journal of Nuclear Medicine.

The study, the largest of its kind using advanced PET/MRI imaging, discovered significant abnormalities in cardiovascular and pulmonary tissues, as well as altered levels of circulating immune-regulating proteins, in long COVID patients. These abnormalities could serve as early warning signs of diseases such as heart failure, valvular heart disease, and pulmonary hypertension.

“Long COVID has emerged as a major public health challenge, and the long-term sequelae remain largely undefined,” says corresponding author Maria G. Trivieri, MD, PhD, Associate Professor of Medicine (Cardiology), and Diagnostic, Molecular and Interventional Radiology at the Icahn School of Medicine. “This study brings us closer to understanding how SARS-CoV-2 affects the heart and lungs over time. We believe long COVID results in an inflammatory response that may predispose patients to premature coronary artery disease, pulmonary hypertension, and valvular damage such as stenosis or regurgitation.”

“Since 2020, we have been publishing work showing that even mild or asymptomatic COVID infections can have serious cardiovascular consequences, even in previously fit and healthy individuals,” says David Putrino, PhD, the Nash Family Director of Mount Sinai’s Cohen Center for Recovery from Complex Chronic Illness. “This paper provides more data to highlight that SARS-CoV-2 is a virus that profoundly affects vascular health and that every new infection can do damage. Infection prevention is crucial.”

Researchers studied 100 adult Mount Sinai patients who had a confirmed COVID-19 infection between December 2020 and July 2021 and were experiencing persistent cardiopulmonary symptoms. Most of these patients had no previous diagnosis of cardiovascular disease. About 300 days after their initial infection, 91 participants underwent hybrid 18F-fluorodeoxyglucose positron emission tomography combined with magnetic resonance imaging (PET/MRI), an advanced imaging method that simultaneously detects structural and metabolic abnormalities. Among those scanned, 52 patients—representing 57 percent—demonstrated evidence of inflammation affecting the heart muscle, pericardium (the thin sac that surrounds the heart), heart valves, particularly the mitral valve, and the aortic and pulmonary blood vessels. In several cases, more than one of these regions was affected.

The PET/MRI scans revealed myocardial (heart muscle) abnormalities in 22 participants, characterized by scarring and thickening of the tissue, similar to findings of myocarditis or cardiomyopathy. Pericardial involvement was seen in 20 patients, indicating either inflammation or effusion, a buildup of fluid. Inflammation near the mitral valve was identified in 10 participants, and vascular inflammation involving the aorta or pulmonary arteries was observed in 28 participants. All abnormalities were associated with persistent symptoms such as chest pain, fatigue, and shortness of breath.

In parallel, researchers performed plasma protein analysis, which showed abnormal patterns in key biomarkers that regulate inflammation and immune signaling. These findings correlated with the imaging abnormalities, providing molecular-level confirmation of persistent inflammation.

To further validate the results, a control group of nine individuals with confirmed prior COVID-19 infection but no lingering cardiopulmonary symptoms was studied between March and October 2023. These controls underwent the same imaging and blood testing and did not exhibit the inflammatory changes observed in the symptomatic long COVID cohort.

“We found a range of cardiopulmonary inflammatory patterns, backed by abnormal protein profiles,” Dr. Trivieri says. “These insights could have far-reaching implications for diagnosis and surveillance. If patients experience lingering symptoms such as shortness of breath, they should consult a physician for further evaluation. Our results should also raise awareness among clinicians to consider a patient’s COVID history and evaluate persistent symptoms more thoroughly.”

Zahi Fayad, PhD, senior author of the study and Director of the Biomedical Engineering and Imaging Institute at the Icahn School of Medicine at Mount Sinai, emphasized the broader impact of these findings. “This study highlights the unique power of hybrid PET/MRI imaging to uncover hidden disease processes in long COVID patients,” Dr. Fayad says. “These findings should change how we approach care and surveillance-not only recognizing SARS-CoV-2 as a potential long-term cardiovascular risk factor, but also integrating molecular imaging into post-COVID evaluation protocols. We now have objective evidence that can guide earlier detection and potentially prevent future cardiopulmonary events.”

The Mount Sinai team continues to follow this patient cohort to assess long-term outcomes and is exploring whether these imaging and biomarker patterns can help predict who is most at risk for developing chronic cardiovascular or pulmonary disease after COVID-19.

Reference:

Maria Giovanna Trivieri et al, Prevalence of Persistent Cardiovascular and Pulmonary Abnormalities on PET/MRI and DECT Imaging in Long COVID Patients, Journal of Nuclear Medicine (2025). DOI: 10.2967/jnumed.124.268980.

A single blood test, designed to pick up chemical signals indicative of the presence of many different types of cancer, could potentially thwart progression to advanced disease while the malignancy is still at an early stage and amenable to treatment in up to half of cases, suggests a modelling study published in the open access journal BMJ Open.

Incorporating the test, formally known as a multi-cancer early detection test, or MCED for short, either yearly or biennially, could therefore improve outcomes for patients by intercepting disease progression, suggest the researchers.

Currently, only a few cancers can be reliably screened for-those of the breast, bowel, cervix (neck of the womb), and lung for those at high risk. While effective at lowering death rates from these diseases, these screens can also result in false positive results and overdiagnosis, say the researchers.

The optimal interval at which screening will pick up the most cancers at an early stage (I and II) while at the same time avoiding unnecessary testing and treatment still isn’t clear.

To inform future clinical trials, the researchers drew on a previously published disease progression model for many different cancers. They used this to predict the impact of regular screening with an MCED test on the time of cancer diagnosis and patient death for different screening schedules among 50-79 year olds in receipt of usual care.

The screening schedules modelled ranged from 6 months to 3 years, but with an emphasis on annual and biennial screening for two sets of cancer growth scenarios. These were ‘fast’, where tumours remain at stage I for between 2 and 4 years before progressing; and ‘fast aggressive’ where tumours remain at stage 1 for between 1 and 2 years, with decreasing periods of time for progression to successive stages.

Cancer types included were those of the anus; bladder; breast; cervix; bowel/rectum; food pipe (oesophagus); gallbladder; head and neck; kidney; liver/ bile-duct; lung; ovary; pancreas; prostate; sarcoma (soft tissues/bone); stomach; thyroid; urothelial tract, and uterus, as well as leukaemia, lymphoma, melanoma, blood cancers (myeloid neoplasm, immune cell cancers (plasma cell neoplasm).

The researchers drew on MCED test characteristics from a recently published report and patient outcomes from population cancer data from the US Surveillance, Epidemiology and End Results (SEER) programme.

Their analysis showed that all MCED screening intervals had more favourable early-stage diagnostic rates than usual care alone. There was a larger impact on stage shift for tumours with ‘fast’ growth than for tumours with ‘fast aggressive’ growth.

But annual MCED screening under the fast tumour growth scenario was associated with a higher number of diagnoses: 370 more cancer signals were detected per year per 100,000 people screened, with 49% fewer late-stage diagnoses, and 21% fewer deaths within 5 years than usual care.

While biennial MCED screening was able to shift the stage at diagnosis and avert deaths, it was not as effective as annual screening: 292 more cancer signals were detected/year/100,000 people screened; 39% fewer late-stage diagnoses; and 17% fewer deaths within 5 years than usual care.

Annual MCED screening prevented more deaths within 5 years than biennial screening for the fast tumour growth scenario. But biennial screening had a higher positive predictive value: 54% compared with 43%. In other words ,it picked up more cancers for each completed test.

And it was more efficient at preventing more deaths within 5 years per 100,000 tests-132 compared with 84, although it prevented fewer deaths per year, so was less effective.

Given that 392 people are diagnosed each year with an aggressive cancer that would kill them within 5 years, earlier diagnosis through biennial MCED screening could have averted 54 (14%) of these deaths. But annual MCED screening could have avoided 84 (21%) fewer deaths, say the researchers.

“Based on the performance characteristics from a case control study, both annual and biennial screening with an MCED test have the potential to intercept 31–49% of cancers at stage I-II that would otherwise present at stage III-IV,” they estimate.

“Of these, approximately equal numbers would be detected at stage I and at stage II: 14% stage I and 16% stage II to 23% stage I and 26% stage II.”

The researchers acknowledge that their estimates assume 100% compliance with the recommended screening schedule and 100% accuracy of confirmatory follow up tests, and so represent the upper bounds of potential benefits of MCED cancer screening.

It is also assumed that a reduction in the number of late-stage cancer diagnoses would automatically reduce death rates from the disease. And they point out: “The optimal choice of screening interval will depend on assessments of real-world cancer survival and the costs of confirmatory testing after MCED screening.

“However, both annual and biennial MCED screening intervals have the potential to avert deaths associated with late-stage cancers when used in addition to current guideline-based cancer screening.”

Reference:

https://bmjopen.bmj.com/lookup/doi/10.1136/bmjopen-2024-086648