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Gene involved in heart attacks discovered

A gene that plays a vital role in determining people’s susceptibility to a range of potentially fatal vascular conditions, such as heart attacks, has been pinpointed.
The discovery advances understanding of the underlying causes of a wide range of serious health conditions, including hardening of the arteries, and, say researchers from the University of Virginia’s School of Medicine, moves the medical profession a step closer to new treatments and preventative measures that could help people live longer, healthier lives.
Principal investigator, Clint L Miller, PhD, of UVA’s Center for Public Health Genomics and Departments of Biochemistry and Molecular Genetics and Public Health Sciences, said: “The first step towards translating the knowledge of population risk for vascular disease is disentangling the fundamental cellular processes that could be affected.
“Ideally, this can be done systematically in disease-relevant models. By gaining insight into the gene regulatory networks that underlie specific vascular disease pathways, we can develop more tailored interventions or risk metrics for patients.”
Lifestyle choices such as smoking, sedentary behaviour, and a diet heavy in red meat play major roles in the development of vascular conditions such as coronary artery disease, which is a leading cause of death worldwide.
But inherited genetic material also shapes a person’s risk. Understanding precisely how, however, has been a major challenge for scientists.
This is because the subtle changes that take place in blood vessels over time are extremely complex. In coronary artery disease, for example, scientists have determined that genes that affect risk can be found at more than 300 locations on a person’s chromosomes.
That’s a vast area for scientists to explore.
The new discovery from Clint Miller and his collaborators published in the scientific journal Circulation Research, identifies a gene – known as FHL5 – that directs an entire network of units of heredity and processes.
The research team describe FHL5 as akin to a general deploying troops on the battlefield.
That makes it an extremely attractive molecule for scientists seeking to unravel the targetable pathways for new treatments or prognostic tools as they work to prevent the harmful changes that contribute to vascular diseases.

Clint Miller. Credit: Dan Addison | UVA Communications
Clint Miller said: “We hope this work serves as a template for future studes to investigate the functional consequences of perturbing key regulators in the vessel wall. Translating this knowledge to the clinic will require ongoing interdisciplinary collaborations, and we look forward to ultimately seeing the impact of these genetic studies.”
To understand how the FHL5 encoded protein functions, Clint Miller and his team evaluated its effect on smooth muscle cells, which form the structure of arteries.
They found that when FHL5 was too active, the cells began to accumulate too much calcium – known as calcification.
This is a key step in atherosclerosis, the build-up of harmful plaque in the arteries that can lead to heart attacks, strokes and other serious health problems.
Further, the excess gene activity contributed to other critical cellular activities related to vascular disease.
But FHL5’s role doesn’t stop there. Instead, the scientists found, it has a far-reaching effect on other genes and cellular processes that shape the ‘remodelling’ that occurs in the arteries over time.
“By mapping the downstream effectors of vascular remodelling, we hope to shed light on preventative mechanisms,” Clint Miller explained. “Unbiased genetic studies led us to this specific cofactor.
“However, studying its regulatory network could explain its link to several vascular diseases.”
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Diabetes patients face increased risk of undiagnosed heart failure

People with diabetes may have undiagnosed heart failure that could be detected by a simple screening blood test, research suggests.
The TARTAN-HF trial found that one in four patients with diabetes who had at least one other risk factor for heart failure had undiagnosed heart failure detected through screening with a blood test and ultrasound scanning of the heart.
Experts said the findings show the extent of unrecognised heart failure in people with diabetes, and how the condition can be detected using a widely available blood test called NT-proBNP, which measures how much strain the heart is under.
They suggest a heart failure screening programme for diabetics could improve diagnosis rates, lead to earlier treatment and potentially reduce the risk of hospitalisation and death.
The study, involving 700 patients, was led by the University of Glasgow in collaboration with AstraZeneca, Roche Diagnostics, Us2.ai, NHS Greater Glasgow and Clyde and NHS Lanarkshire.
Dr Kieran Docherty, clinical senior lecturer at the University of Glasgow’s School of Cardiovascular and Metabolic Health, said: “Our results from the landmark TARTAN-HF trial identified heart failure in a large proportion of people living with diabetes, emphasising the need for a heart failure screening strategy in this group of patients.
“We know that many of the symptoms and signs of heart failure are non-specific, and may go unrecognised as potentially being due to heart failure for a long time.
“The strategy used in our trial is simple and easy to implement in clinical practice, and will aid in the early identification of heart failure in people with diabetes, and facilitate the initiation of medications that we know improve outcomes in patients with heart failure.”
The study, which began more than three years ago, involved more than 700 people with diabetes from the two health board areas who had at least one other risk factor for heart failure.
They were randomly assigned either to receive heart failure screening or to continue with their usual care.
Researchers found screening uncovered a large number of previously unrecognised cases of heart failure. Around one in four, or 24.9 per cent, of those screened were found to have the condition within six months, compared with 1 per cent in the group continuing their usual care.
The study, involving patients with type 1 and type 2 diabetes, found almost all of the participants found to have heart failure had preserved ejection fraction, which can be difficult to detect without dedicated testing.
The findings of the TARTAN-HF trial were presented at the American College of Cardiology conference taking place from 28 to 30 March in New Orleans in the US.
Dr Edward Piper, medical director at AstraZeneca UK, said: “Delayed diagnosis and treatment of heart failure in people with type 2 diabetes contributes to poor long-term outcomes. TARTAN-HF demonstrates that targeted, risk-based screening can identify previously undiagnosed heart failure in approximately one in four high-risk patients with diabetes, enabling earlier intervention with guideline-directed therapy.”
Dr Christian Simon, head of global medical affairs at Roche Diagnostics, said: “We are proud to have supported the landmark TARTAN-HF trial. These findings demonstrate the transformative power of early, accessible diagnostics like the NT-proBNP blood test.
“By identifying unrecognised heart failure in people with diabetes, we enable clinicians to initiate appropriate treatments sooner, ultimately improving patient outcomes and lives.”
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UK government announces £6.3m fund to boost men’s health

The UK has launched a £6.3m men’s health fund to back local projects aimed at helping men and boys live longer, healthier lives.
The Men’s Health Community Fund is a partnership between the Department of Health and Social Care, Movember and People’s Health Trust.
The government is contributing £3m, while the two charities are more than doubling that to take the total to £6.3m.
Grants will support community projects reaching underserved men and boys aged 16 and over, particularly in the most disadvantaged areas and at key points in their lives such as becoming a father, losing a job or retiring.
Projects could include support for new fathers, activities for men facing loneliness and social isolation, services to help young men engage with the health system, and support for men in work, out of work and moving into retirement.
The programme will bring together voluntary, community and social enterprise organisations to test new ways of reaching men who are least likely to use traditional health services.
An evaluation funded through the National Institute for Health and Care Research will assess what works and help inform future policy and delivery.
Health and social care secretary Wes Streeting said: “Too many men across the country are living shorter, less healthy lives, particularly those in our most disadvantaged communities.
“This new partnership will help men get the support they need in the places they feel most comfortable, their communities, among people they trust.
“By working with expert charities and local organisations, we can reach the men who are too often missed by traditional services and help them take better care of their mental and physical health.”
“It is a key step in delivering our first ever Men’s Health Strategy and driving forward our ambition to halve the gap in healthy life expectancy between the richest and poorest areas.”
The Men’s Health Strategy sets out plans to tackle the physical and mental health challenges men and boys face.
Men can be less likely to seek help and more likely to suffer in silence, while higher rates of smoking, drinking, gambling and drug use are damaging men’s health and affecting families, workplaces and communities.
The government is also investing £3.6m over the next three years in suicide prevention projects for middle-aged men in local communities across areas of England where men are most at risk, many of which are also among the most deprived. Suicide is one of the biggest killers of men under 50, and three-quarters of all suicides are men.
The projects will aim to break down barriers middle-aged men face in seeking support, including stigma around asking for help and a lack of awareness of what is available and how to access it.
They will be co-designed with experts and men with lived experience of mental health crises and suicidal thoughts.
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