Tag: Cardiovascular Disease

Resistant starch diet proves a game changer for weight loss and diabetes control
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In a recent study published in the journal Nature Metabolism, a team of scientists investigated whether modulation of the gut microbiome using dietary fiber supplementation in the form of resistant starch could help with insulin resistance and weight loss and offer a potential treatment avenue for metabolic disorders.

Study: Resistant starch intake facilitates weight loss in humans by reshaping the gut microbiota. Image Credit: Sokor Space / Shutterstock

Background

Obesity has been classified as a global epidemic, with substantial research being conducted on strategies to reduce weight and prevent obesity. It contributes significantly to the global mortality rates by increasing the risk of metabolic diseases such as diabetes, as well as cardiovascular disease risk. Weight management and effective weight loss can lower the risk of these diseases.

Increasing evidence indicates that the gut microbiome plays a pivotal role in the regulation of human physiology and development of various diseases. Gut microbiome composition and diversity are intricately linked to the metabolism of glucose and fat and inflammation.

Furthermore, while fecal microbiome transplantation has been used to establish healthy gut microbiome communities, the procedure has not yielded effective or long-term results. However, diet can be used to modulate the gut microbiome, and dietary interventions, either alone or in conjunction with fecal microbiome transplantation, could potentially improve the clinical outcomes.

About the study

In the present study, the team conducted a randomized, crossover clinical trial involving overweight individuals to determine whether dietary supplementation with resistant starch positively impacted obesity and metabolic phenotypes. They also conducted metagenomic and metabolomic analyses to understand how the resistant starch affected the composition of the gut microbiome and its function.

Furthermore, they studied antibiotic-treated mice that had received gut microbiomes from human donors that had already been modified through resistant starch supplementation to understand how gut microbiomes modified through supplementation with resistant starch influence glucose metabolism and adiposity. The metabolomic advantages offered by the gut microbiome modified through resistant starch supplements were also explored.

Resistant starch cannot be broken down by the amylase enzymes produced in humans, functioning as a dietary fiber. During digestion, resistant starch does not get broken down in the stomach or small intestine but moves into the large intestine or colon, where the gut microbiome ferments this dietary fiber. Rodent model studies have shown a decrease in body fat and better metabolic outcomes when the carbohydrate portion of their diet consists mainly of resistant starch.

The present clinical trial included participants with excess body weight who did not have any chronic disorders, were not using any probiotics or antibiotics, and were not undergoing any treatments that would impact their glucose metabolism. The participants were randomly assigned to the treatment or control group, with the treatment group receiving resistant starch in the form of high-amylose maize and the control group receiving amylopectin with no resistant starch.

The starch was provided in sachets in powdered form, and all the participants in the treatment and control groups consumed one packet of the appropriate starch twice a day before a balanced, isoenergetic meal that was provided thrice a day. Since this was a crossover clinical trial, all the participants underwent two eight-week-long interventions, one for the resistant starch treatment and the other for the control treatment.

Results

The results showed that supplementation with resistant starch helped achieve a mean weight loss of about 2.8 kg and improved insulin resistance in overweight participants. The study also found that the beneficial effects of resistant starch supplementation were associated largely with gut microbiome composition changes.

The bacterium Bifidobacterium adolescentis was found to be associated with resistant starch supplementation in humans, and the monocolonization of mice with this bacterium protected them from diet-induced obesity. Resistance starch impacted lipid and fat metabolism by reducing inflammation, restoring the intestinal barrier, and altering the bile acid profile.

The gut microbiota impacts the host physiology through signaling metabolites, of which bile acids play a significant role. Secondary bile acids, such as glycodesoxycholic acid, deoxycholic acid, glycocholic acid, and taurodeoxycholic acid, are important in improving insulin sensitivity and ameliorating hepatic steatosis. The enzyme bile salt hydrolase carries out the deconjugation of secondary bile acids.

The study found that resistant starch supplementation decreased the production of bile salt hydrolase and increased the levels of secondary bile acids. The results were reciprocated in the mice after they were monocolonized with B. adolescentis from humans who underwent resistant starch supplementation.

Resistant starch (RS, 40 g d^-1) accompanied with isoenergetic and balanced diets led to an obvious reduction in body weight and improvement of insulin sensitivity, as well as alteration in metagenomics and metabolomics. Faecal microbiota transplantation (FMT) showed benefits of RS were associated with the reshaped gut microbiota composition. Monocolonization of mice with B. adolescentis, which was closely correlated with the benefits of RS in human protected mice from diet-induced obesity. Mechanistically, the RS-induced changes in the gut microbiota influenced metabolites of gut microbiome, reduced chronic low-grade inflammation by improving intestinal integrity, inhibited lipid absorption by modulating angiopoietin-like 4 (ANGPTL4), and improved the sensitivity of fibroblast growth factor 21 (FGF21) in adipose tissue. SPF, specific-pathogen-free; LPS, lipopolysaccharide; BCAAs, branched-chain amino acids; Erk1/2, extracellular signal-regulated kinase 1/2; FGFR1, fibroblast growth factor receptor 1. Created with BioRender.com.

Conclusions

To summarize, the study found that supplementation with resistant starch can facilitate weight loss by increasing the abundance of B. adolescentis in the gut microbiome. It can also help improve insulin sensitivity through gut microbiome-induced changes in the levels of secondary bile acids and lowering of inflammation.
Journal reference:

Li, H., Zhang, L., Li, J., Wu, Q., Qian, L., He, J., Ni, Y., KovatchevaDatchary, P., Yuan, R., Liu, S., Shen, L., Zhang, M., Sheng, B., Li, P., Kang, K., Wu, L., Fang, Q., Long, X., Wang, X., & Li, Y. (2024). Resistant starch intake facilitates weight loss in humans by reshaping the gut microbiota. Nature Metabolism. DOI: 10.1038/s4225502400988y, https://www.nature.com/articles/s42255-024-00988-y
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February 28, 2024
Cardiovascular health variances in women’s lifespan
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Women’s cardiovascular disease risks and outcomes differ throughout the lifespan from those of men, according to a collection of studies devoted to cardiovascular medicine research focused on women of all ages, published today in a special “spotlight” issue of the Journal of the American Heart Association, an open access, peer-reviewed journal of the American Heart Association.

Cardiovascular disease kills more women than all forms of cancer combined. Among females 20 years and older, nearly 45% are living with some form of cardiovascular disease, and less than 50% of women entering pregnancy in the U.S. have good heart health. In addition, more than half of deaths from high blood pressure are in women. Yet, women make up only 38% of participants in cardiovascular disease clinical trials, according to the American Heart Association.

The special Go Red for Women issue of the Journal, in recognition of American Heart Month, features studies that reveal insights such as: how diet may affect the high preeclampsia risk in pregnant Hispanic/Latina women; how women were less likely than men to receive bystander CPR and automated external defibrillator (AED) treatment, as well as survive the first 30 days post-hospitalization after out-of-hospital cardiac arrest; and how rehospitalization rates differ in women with heart failure and obstructive sleep apnea. In yet another study featured, researchers report that while the incidence of intracerebral hemorrhage (bleeding within the brain), the second most common stroke type, was lower in women, women were more likely to die one year after a stroke than men.

Below are highlights of some of the manuscripts in this issue,
- Prospective Associations of Accelerometer-measured Machine-learned Sedentary Behavior with Mortality among Older Women: The OPACH Study
Steve Nguyen, Ph.D., et al.; University of California, San Diego, La Jolla, California

This team studied sedentary behavior patterns in nearly 6,000 older women (average age 79 years) to determine the impact of sitting time on death from cardiovascular disease and all causes. Using a measurement tool powered by machine learning to accurately classify sitting time, researchers found those who sat more than 11.6 total hours a day and had longer bouts of uninterrupted sitting had a 57% higher risk of death from all causes and a 78% increased risk of death from cardiovascular disease. This was compared to women who sat less than 9.3 hours a day. The increased risk of death was consistent regardless of age, body mass index, physical functioning, cardiovascular disease risk factors, physical activity intensity and race/ethnicity. Reducing overall sedentary behavior and uninterrupted sitting time would likely have large public health benefits in an aging society, according to researchers.
- Sex Differences in the Relationship between Schizophrenia and the Development of Cardiovascular Disease
Hidehiro Kaneko, M.D., Ph.D., et al.; University of Tokyo, Tokyo, Japan

Researchers studied cardiovascular disease risk in people with schizophrenia, a serious psychotic disorder and one of the top 15 leading causes of disability worldwide. Schizophrenia results in severe, chronic mental illness characterized by disturbances in perception, thought and behavior. The study found a strong association between schizophrenia and risk of developing cardiovascular disease in adults, but particularly in women. This higher risk in women may be related to hormonal changes during pregnancy and menopause, or reports that women are more sedentary than men. Nevertheless, the findings point to the need for health care professionals to take a thorough and gender-focused approach to cardiovascular disease prevention due to the notable role schizophrenia seems to play in cardiovascular disease. The researchers suggest that it’s crucial to promote physical activity, especially among women with schizophrenia, as inactivity may have increased the risk in female participants in this study. Healthcare providers should routinely screen and treat schizophrenia as part of standard clinical practice, with special attention to women, authors wrote.
- Maternal Dietary Patterns During Pregnancy Are Linked to Hypertensive Disorders of Pregnancy Among a Predominantly Low-Income US Hispanic/Latina Pregnancy Cohort
Luis E. Maldonado, Ph.D., M.P.H., et al.; Keck School of Medicine, University of Southern California

In a study of more than 400 predominantly low-income, pregnant Hispanic/Latina women in Los Angeles, researchers found that a diet characterized by higher intakes of solid fats, refined grains and cheese was strongly associated with greater odds of having had a hypertensive disorder of pregnancy including preeclampsia during pregnancy.

Other papers in the spotlight issue include:
- Association of Sex With Cardiovascular Outcomes in Heart Failure Patients With Obstructive or Central Sleep Apnea -; Jian Zhang, M.D., Ph.D., et al.; Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Pregnancy History at 40 Years of Age as a Marker of Cardiovascular Risk -; Liv G. Kvalvik, M.D., Ph.D., et al.; University of Bergen, Bergen, Norway
- Sex Differences in the Epidemiology of Intracerebral Hemorrhage Over 10 Years in a Population-Based Stroke Registry -; Simona Sacco, M.D., et al.; University of L’Aquila, L’Aquila, Italy
- Sex Differences in Revascularization, Treatment Goals, and Outcomes of Patients With Chronic Coronary Disease: Insights From the ISCHEMIA Trial -; Harmony R. Reynolds, M.D., FAHA, et al.; NYU Grossman School of Medicine, New York City
- Sex Differences in Receipt of Bystander CPR Considering Neighborhood Racial and Ethnic Composition -; Audrey L. Blewer, Ph.D., M.P.H., et al.; Duke University, Durham, North Carolina
- Hypertension in Pregnancy among Immigrant and Swedish Women – A Cohort Study of All Pregnant Women in Sweden -; Axel C. Carlsson, Ph.D., et al.; Karolinska Institutet, Huddinge, Sweden
- Sex Differences In Out-of-Hospital Cardiac Arrest Survival Trends -; R. L. A. Smits, et al.; Amsterdam University Medical Center, Amsterdam, The Netherlands;
- Posttraumatic Stress Disorder is Associated With Elevated Risk of Incident Stroke and Transient Ischemic Attack in Women Veterans -; Ramin Ebrahimi, M.D., et al.; University of California, Los Angeles; Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles; and
- Sex differences in Outcomes of Acute Myocardial Injury After Stroke -; Michela Rosso, M.D., et al.; University of Pennsylvania, Philadelphia.
Source:

American Heart Association

Journal reference:

Mujahid, M. S. & Peterson, P. N., (2024) JAHA Go Red for Women Spotlight on Women and Cardiovascular Disease and Stroke. Journal of the American Heart Association. doi.org/10.1161/JAHA.124.035104.
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February 27, 2024
Spirulina shows promise in battling heart disease and diabetes
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In a recent study published in the journal Nutrients, a team of Italian researchers reviewed clinical and experimental findings from recent studies to understand the therapeutic contributions of Spirulina, also called blue-green cyanobacteria, in managing cardiovascular disease and its risk factors.

Study: Beneficial Effects of Spirulina Supplementation in the Management of Cardiovascular Diseases. Image Credit: baibaz / Shutterstock

Background

Although Spirulina has recently gained popularity as a ‘superfood’ because of its high nutritional content, the use of microalga in diet dates back to the ancient times of the Aztecs in Mexico. Spirulina is also known as blue-green cyanobacteria and are microscopic, photosynthesizing, filamentous microalgae of the genus Arthrospira, with A. plantensis and A. maxima being the two species most commonly used for their therapeutic and nutritional value.

They grow in the tropics, in alkaline lakes with high bicarbonate and carbonate salt concentrations, although they have been known to survive in extremely cold temperatures. Spirulina is considered a ‘superfood’ because 60% to 70% of its dry weight is composed of protein, while it is also abundant in minerals, vitamins, carbohydrates, phycocyanin, carotenes, and fatty acids. As a nutraceutical, it has been added to various types of foods, including sports supplements and baby foods, while the pharmaceutical industry has popularized it in the form of capsules, dehydrated powders, and tablets.

Therapeutic effects of Spirulina

Research indicates that Spirulina exhibits a wide range of therapeutic effects such as anti-inflammatory, antidiabetic, antioxidant, hypolipidemic, and neuroprotective properties. The antioxidant properties are attributed mainly to the pigments phycocyanin, β-carotene, diatoxanthin, and diadinoxanthin found in Spirulina.

Given its hypolipidemic and antioxidant properties, supplementation with Spirulina could be beneficial in lowering the risk of cardiovascular disease. Furthermore, diabetes, along with dyslipidemia and hypertension, is one of the risk factors for cardiovascular disease. Therefore, the present review examined how the cumulative health benefits of Spirulina could lower the overall risk of cardiovascular disease, which continues to be one of the major causes of mortality across the globe.

Beneficial effects of Spirulina in CVDs.

Spirulina and hypertension

The impact of Spirulina in lowering the risk of hypertension and stroke has been studied extensively in clinical trials, and the findings from these studies have shown that daily consumption of Spirulina, even added to foods such as salad dressing, significantly reduced the diastolic and systolic blood pressure.

Consumption of Spirulina in the form of nutraceutical tablets also showed similar hypotensive results. Furthermore, animal studies using hypertensive rat models have shown that the high silicon content of Spirulina could be responsible for improving the elasticity of the arterial walls, along with angiotensin-converting enzyme-inhibiting properties that result in hypotensive effects.

Antidiabetic effects of Spirulina

Diabetes mellitus increases the risk of cardiovascular events such as heart failure, myocardial infarction, stroke, and peripheral vascular disease due to the micro- and macrovascular consequences of hyperglycemia. Cellular membrane integrity is also impacted by hyperglycemia, causing the peripheral tissues and liver to become insulin-resistant, increasing the generation of reactive oxygen species.

In comparison to metformin, which is the standard treatment for hyperglycemia during diabetes, supplementation with Spirulina is believed to not only lower the levels of circulating glucose but also have a positive impact on lipid metabolism, which is linked to diabetes. The hypoglycemic and hypolipidemic properties of Spirulina are believed to have a cumulative effect in decreasing the risk of cardiovascular disease.

The review discussed various clinical trials and studies using animal models of diabetes mellitus that have investigated the hypoglycemic properties of Spirulina and compared its efficacy in lowering blood sugar levels with that of metformin.

While the mechanism through which Spirulina impacts blood glucose levels is not yet fully understood, the researchers believe that it could be influencing the secretion of insulin from the β-cells in the islets of Langerhans in the pancreas or further downstream, facilitating the transport of glucose from blood to all the peripheral tissue.

Hyperlipidemia and Spirulina

Spirulina has also demonstrated hypolipidemic properties by lowering the concentrations of low-density-lipoprotein cholesterol and triglycerides in the plasma while increasing the levels of high-density lipoprotein cholesterol, with the beneficial effects not being dose-dependent or toxic at high concentrations.

Studies in animal models and overweight or obese human participants have reported significant benefits of Spirulina supplementation in lowering triglyceride levels, either as food additives or as nutraceutical pills or tablets. Spirulina was also found to be beneficial as an adjunct therapy to metformin in overweight diabetes patients.

Conclusions

Overall, this comprehensive review reported that consumption of Spirulina, either as an additive to regular foods or as a nutraceutical supplement, had numerous potential benefits, such as hypoglycemic, antioxidant, and hypolipidemic effects. However, the dosage and timing of Spirulina supplementation need to be standardized for optimal benefits in lowering the risk of cardiovascular disease.

In conclusion, based on these data, more rigorous studies should be planned in the future aiming to address these critical questions, putting the foundations for developing a common guideline on “how and when” to use Spirulina.
Journal reference:

Prete, V., Abate, A. C., Pietro, D., Lucia, D., Vecchione, C., & Carrizzo, A. (2024). Beneficial Effects of Spirulina Supplementation in the Management of Cardiovascular Diseases. Nutrients, 16(5). DOI: 10.3390/nu16050642, https://www.mdpi.com/2072-6643/16/5/642
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February 27, 2024
Flavonol-rich diet linked to lower mortality and disease risk, study shows

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In a recent prospective cohort study published in the journal Scientific Reports, researchers investigated the association between flavonol intake and cause-specific and all-cause mortality risk in adults in the United States. They found that an elevated dietary intake of flavonol is associated with a lower risk of all-cause mortality as well as Alzheimer’s disease (AD), cancer, and cardiovascular disease (CVD)-related mortality risk.

Study: Flavonol-rich diet linked to lower mortality and disease risk, study shows. Image Credit: sematadesign / Shutterstock

Background

Flavonoids are biologically active polyphenolic compounds found in various plant-based foods. Among the six subclasses of flavonoids, flavonols are the most prevalent and active. Primary flavonols like quercetin, kaempferol, myricetin, and isorhamnetin are abundant in tea, onions, and berries. The consumption of flavonoids is known to potentially enhance endothelial function, maintain nitric oxide status, and influence biological processes relevant to lipid metabolism, platelet function, inflammation, oxidative stress, and blood pressure. Additionally, flavonoids are also known to exhibit anti-tumor effects by targeting key molecules and pathways, leading to apoptosis and inhibiting cell growth and metastasis.

However, the relationship between flavonol intake and mortality risk has not been studied thoroughly so far. Therefore, using data from the National Health and Nutrition Examination Survey (NHANES) database, researchers in the present study explored the relationship between flavonol intake (total flavonol, kaempferol, myricetin, isorhamnetin, and quercetin), all-cause mortality risk, and cause-specific mortality risk (AD, CVD, cancer, and diabetes mellitus (DM)).

About the study

The study included 11,679 individuals aged≥ 20 who completed questionnaires, in-person assessments, and laboratory tests. The exclusion criteria were lack of flavonol intake and missing basic and demographic information. Flavonol intake data for the present study were derived from the US Department of Agriculture Survey Food and Beverage Flavonoid Values database (2003–2004). Detailed dietary interviews were conducted to capture information on foods and beverages consumed in the preceding 24 hours. The precise amounts of total flavonols were estimated in various foods, and the daily flavonol intake of participants was calculated.

For mortality analysis, data from the National Death Index file and the 2019 Public Access Link mortality dataset were used. Mortality was categorized by causes such as cancer, CVD, DM, AD, and other causes, as per the International Statistical Classification of Diseases and Related Health Problems 10 (ICD-10) codes. Follow-up was conducted from the interview date to either the date of death or the study’s conclusion on December 31, 2019. Participants were stratified based on sociodemographic variables, including age, sex, race/ethnicity, marital status, education level, poverty ratio, alcohol consumption, body mass index (BMI), disease history, and the presence of various health conditions. Statistical analysis involved the use of Cox regression, Fine and Gray competing risks regression models, hazard ratios (HR), chi-square tests, and sensitivity analyses.

Results and discussion

Participants with the highest total flavonol intake tended to be male, younger, Non-Hispanic White, married, educated, above the poverty line, alcohol consumers, with BMI 18.5–30.0 kg/m² and had a history of DM, hypertension, hyperlipidemia, congestive heart failure, coronary heart disease, angina, heart attack, and stroke. Increasing total flavonol intake showed a declining trend in all-cause mortality as well as AD, cancer, and CVD-specific mortality (p < 0.05 for all). Similar decreasing trends were observed for isorhamnetin, kaempferol, and quercetin intakes across various mortality categories, while myricetin intake exhibited a decreasing trend in AD mortality.

While higher age was associated with a significant increase in all-cause mortality, female gender was found to be significantly linked to a lower risk of all-cause mortality. Conversely, a history of diseases was significantly associated with a higher risk of all-cause mortality.

Further, higher total flavonol intake, particularly isorhamnetin, kaempferol, myricetin, and quercetin, was found to be associated with a reduced risk of all-cause and mortality owing to AD, CVD, cancer, and other causes. However, no correlation was found between flavonol intake and DM-specific mortality (p>0.05). The findings from the subgroup and sensitivity analyses aligned with the study’s main findings.

Although the study is strengthened by its use of a multiple confounder-adjusted competing risks model to address competing risks of death, the study is limited by missing flavonol intake data, potential lack of generalizability, lack of data on primary food sources and dietary patterns, and the lack of exclusion of micronutrient supplement intake.

Conclusion

In conclusion, the present study establishes an association between dietary flavonol intake and overall mortality as well as cancer, AD, and CVD-specific mortality risk in US adults. The findings suggest that flavonol intake could be employed as an independent and reliable predictor of disease survival, offering patients the potential for health- and risk-management through dietary modifications.

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February 27, 2024
Genetic variants influence blood pressure from early in life

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Certain genes associated with hypertension affect blood pressure from early in life, and they increase the risk of cardiovascular disease as you get older. However, you can do something about it.

We are talking about really small differences, so small that they may fall within what is considered normal blood pressure. The problem is that they tend to last your whole life.”

Karsten Øvretveit, PhD Candidate at the Norwegian University of Science and Technology’s (NTNU) Department of Public Health and Nursing

He is one of the researchers behind a new study that has looked at the relationship between gene variants and blood pressure in the population.

The study shows that high blood pressure occurs in all age groups and that it is related to hereditary factors.

“We found that genetic factors affect blood pressure from the first years of childhood and throughout your entire life,” says Øvretveit.

Genetic data from large population studies

High blood pressure is the main cause of heart attacks and strokes, and cardiovascular disease is the second most common cause of death in Norway, accounting for 23 per cent of all deaths in 2022.

The direct medical cause of high blood pressure is unknown in many cases, but research shows that our genes play a signifcant role.

“Lifestyle diseases are often caused by a combination of heredity and environment. Diseases are often the result of not only one, but very many genetic variants,” says Øvretveit.

In order to find out how much a person is at risk of high blood pressure, researchers have used genetic data from large population studies. This has helped them develop a genetic risk score, which indicates how much your exact genetic makeup puts you at risk.

Developing genetic risk scores

Put very simply, a certain value is placed on each gene variant, which reflects the extent to which it can affect blood pressure. The variants are then “weighted”, i.e. some genes weigh more heavily than others, and the genetic risk score is then the sum of the genetic effects.

“This is how people who are particularly at risk can be identified, and measures can be taken at an early stage before the condition is expressed.

By keeping their blood pressure alow level, people with a high genetic risk score can achieve a lower risk of disease than people diagnosed with high blood pressure who we consider genetically protected,” says Øvretveit.

To study the significance of the genetic risk, the researchers have used health data from participants in the HUNT Study from Trøndelag and from the British ‘Children of the 90s’ study. The latter includes health data from nearly 14,000 children from the time they were born until they were in their twenties. The Health Survey in Trøndelag (HUNT) is a large, Norwegian population-based health survey that includes health information and biological material from the inhabitants of Trøndelag. Since the first collection round in 1984, 250,000 people from Trondheim have participated.

By comparing the blood pressure of the children who had the highest genetic risk with the children who were lowest on the scale, the researchers were able to see how the average blood pressure in the first group was higher from as early as the age of three. The difference lasted throughout their childhood and became more pronounced in adulthood.

Difference increases with age

“Although the differences in blood pressure are not very large, the time component is important. If your blood pressure is slightly elevated over many years, it will affect how prone you are to cardiovascular disease and kidney disease,” says Øvretveit.

When the researchers compared the risk scores and health data of the HUNT Study participants, they saw that the differences in blood pressure between the participants with the highest and those with the lowest risk persisted throughout their whole lives.

“We have been able to follow the same people from when they were around 37 until they were approximately 70 years old. We found that the differences persisted and resulted in various disease risks, where the differences in disease were quite large.”

The researchers also found more positive results: if measures are taken, such as lifestyle changes and medications, the risk of disease can be significantly reduced.

“By keeping their blood pressure at a low level, people with a high genetic risk score can achieve a lower risk of disease than people diagnosed with high blood pressure who we consider genetically protected. It seems that controlling your blood pressure matters more than genetics,” says Øvretveit.

Large population studies provide good data

As a basis for the study, Øvretveit and colleagues have used findings from the largest genetic study on blood pressure currently available, which includes data from over a million people. Øvretveit believes the study shows the possibilities that lie in genetic data from large population studies.

“I don’t think you should start measuring blood pressure in every single child, but the type of data we have used in this study can be used in the future not only to prevent disease, but also to address the risk factors associated with a disease,” says Øvretveit.

Is it a problem that Europeans are overrepresented in population studies?

“Yes, it is, but we are now actively working on developing genetic risk scores that are adapted to other populations, and that can be used across many different populations,” says Øvretveit.

To date, the researchers have identified around 1500 gene variants that have a clear connection with blood pressure, but the biological effect that many of these genes have on blood pressure is not known. In order to find a reliable method, the researchers had to identify high-risk combinations of gene variants and combinations that posed a lower risk through a process of trial and error.

“A common method for creating a risk score for genetic disease is to include only those gene variants that are known to have a strong connection with the disease,” says Øvretveit.

But there are other methods such as including gene variants that produce effects we are more uncertain about. As a result, we get a lot more data in the calculation.

“Complex blood pressure traits may be affected by far more gene variants than we have identified so far. The methods we have developed allow this to be taken into account, but we also have to keep in mind that the individual effects of these variants are small,” says Øvretveit.

The method that gave the most accurate risk score included over a million gene variants.

“But there are far more that have a known connection with high blood pressure,” says Øvretveit.

Source:

Norwegian University of Science and Technology

Journal reference:

Øvretveit, K., et al. (2023). Polygenic risk scores associate with blood pressure traits across the lifespan. European Journal of Preventive Cardiology. doi.org/10.1093/eurjpc/zwad365.

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February 24, 2024
Researchers identify potential treatment for cardiovascular disease linked to Type 2 diabetes
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New research at the Roy Blunt NextGen Precision Health building has discovered a potential treatment for an underlying cause of cardiovascular disease in people with Type 2 diabetes.

More than 30 million Americans live with Type 2 diabetes. One common feature of diabetes is the hardening and inflexibility of blood vessels caused by damage to the endothelial cells in the vascular system. Over time, this can lead to the development and progression of cardiovascular disease, which is the number one cause of death in diabetics. Because endothelial dysfunction is causally linked to cardiovascular disease, there is a considerable need to identify new therapeutic targets to improve endothelial function in Type 2 diabetics.

A research team from the University of Missouri has found that neuraminidase activity is elevated in the circulation of Type 2 diabetic mice and humans. In a series of mechanistic experiments in cultured endothelial cells and isolated blood vessels, they were able to link increased neuraminidase to endothelial dysfunction.

Because we know that Type 2 diabetics have this increased neuraminidase circulating in their blood, and that the presence of it promotes endothelial dysfunction, it is important to target it as a means of addressing the cardiovascular complications faced by those with Type 2 diabetes.”

Luis Martinez-Lemus, DVM, PhD, James O. Davis distinguished professor in cardiovascular research at the University of Missouri School of Medicine

The team also found that neuraminidase inhibition using zanamivir, an oral inhalation drug used to treat the flu virus, improved endothelial function in diabetic mice.

“This research lays out the molecular mechanisms by which neuraminidase promotes endothelial dysfunction and these mechanisms can be exploited therapeutically,” said Jaume Padilla, PhD, an associate professor of nutrition and exercise physiology at MU. “Improving vascular function in people with Type 2 diabetes can help them live longer and better lives, which is why this research is so important.”

“Neuraminidase inhibition improves endothelial function in diabetic mice” and “Neuraminidase-induced externalization of phosphatidylserine activates ADAM17 and impairs insulin signaling in endothelial cells” were recently published in the American Journal of Physiology-Heart and Circulatory Physiology. In addition to Martinez-Lemus and Padilla, the research team at MU includes Camila Manrique-Acevedo, MD, distinguished professor in diabetes and director of faculty research at the School of Medicine; Larissa Ferreira-Santos, PhD, Thaysa Ghiarone, PhD and Francisco Ramirez-Perez, PhD, postdoctoral fellows at NextGen Precision Health; Christopher Foote, PhD, assistant research professor of medical pharmacology and physiology; James Smith, Marc Augenreich, Neil McMillan, and Gavin Power, doctoral students in Nutrition and Exercise Physiology; Andrew Wheeler, MD, surgeon, MU Health Care Weight Management Center; Katherine Burr, senior research specialist at the School of Medicine; Annayya Aroor, MD, assistant research professor at the School of Medicine; Shawn Bender, PhD, associate professor, College of Veterinary Medicine; Mariana Morales-Quinones, PhD, senior research specialist at NextGen Precision Health; Morgan Williams and Juan Gonzalez-Vallejo, NextGen Precision Health.
Source:

University of Missouri-Columbia

Journal references:

Foote, C. A., et al. (2023). Neuraminidase inhibition improves endothelial function in diabetic mice. American Journal of Physiology-Heart and Circulatory Physiology. doi.org/10.1152/ajpheart.00337.2023.

Ferreira-Santos, L., et al. (2024). Neuraminidase-induced externalization of phosphatidylserine activates ADAM17 and impairs insulin signaling in endothelial cells. American Journal of Physiology-Heart and Circulatory Physiology. doi.org/10.1152/ajpheart.00638.2023.
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February 23, 2024
Major study of 59 million Americans finds fine particulate matter from air pollution increases heart disease risks

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In a recent study published in BMJ, researchers assessed exposure-response relationships between chronic fine-size particulate matter (PM2.5) exposure and the probability of first-time hospitalization for cardiovascular disease (CVD) subgroups.

Study: Exposure-response associations between chronic exposure to fine particulate matter and risks of hospital admission for major cardiovascular diseases: population based cohort study. Image Credit: Kzenon/Shutterstock.com

Background

PM2.5, a minor component of air pollution, contributes considerably to CVD by inducing inflammation, vasoconstriction, cardiac electrical abnormalities, and blood clot formation.

Chronic exposure raises the risk of CVD-related hospitalization and death. Studies frequently focus on one or two CVD subtypes, neglecting to detect susceptible ones.

Comparing effect sizes across subtypes might help us understand processes and advise targeted strategies to lessen the impact of PM2.5.

About the study

In the present population-based cohort study, researchers evaluated exposure-response correlations between chronic PM_2.5 exposure and the probability of initial hospitalization for seven main CVD subtypes and their composite.

The study covered Medicare beneficiaries aged 65 years and above in the continental United States (US) from 2000 to 2016. The team linked calibrated fine particulate matter estimations to each participant’s residence postal code as a proxy for exposure assessment.

The primary outcome measures were the initial hospitalization risks for cerebrovascular diseases, ischemic heart diseases, cardiomyopathy, heart failure, valvular heart diseases, abdominal and thoracic aortic aneurysms, arrhythmia, or a combination of these cardiovascular disease subtypes.

The researchers created a causal-type framework resistant to confounding effects and bias caused by inaccuracies in exposure-response estimations.
The study included Medicare beneficiaries aged 65 years and above residing in the United States (US) and registered with the fee-for-service program from 2000 to 2016.

The researchers created a distinct cohort for each CVD subtype by tracking each beneficiary annually till the initial hospitalization for that CVD subtype, death, or study termination, whichever came first.

They created another study cohort by monitoring each beneficiary year till the initial hospitalization for the examined CVDs, mortality, or study termination, whichever occurred first, to investigate the risk of the initial hospitalization for the composite CVD outcome.

The researchers utilized spatially weighted logistic regressions to estimate ambient PM2.5 values daily at 1.0 km2 grids across the United States from 2000 to 2016.

They blended predictions from machine-learning-based algorithms and incorporated information sources such as weather, satellite imagery, land use factors, monitoring information, and chemical model simulations.

They used regression calibrations to improve grid-level particulate matter estimations and eliminate biases in health-effect estimations caused by exposure errors.

Results

The research included 59,761,494 individuals with 476,953,892 follow-up years; the majority were white (84%), with a higher number of female beneficiaries (55%). Most participants (75%) were between the ages of 65 and 74 when they began the research.

During the trial, 18% of participants registered with Medicaid. 22% required hospitalization due to a combination of cardiovascular diseases. The most frequent CVD subtype was ischemic heart illness, which affected 8.8% of recipients.

Other common illnesses were cerebrovascular disease (7.7%), heart failure (6.6%), and arrhythmia (6.5%). Three-year mean exposure to PM2.5 was related to an increase in the relative risk of initial hospitalization for cerebrovascular illnesses, ischemic heart diseases, cardiomyopathy, heart failure, abdominal and thoracic aortic aneurysms, and arrhythmia.

Exposure-response curves for composite cardiovascular disease showed a monotonically elevated risk related to fine particulate matter exposure.

Compared to exposures ≤5.0 µg m-3 [air quality standard issued by the World Health Organization], the relative risks at exposures ranging from 9.0 to 10 µg m-3, encompassing the United States mean of 9.70 µg m-3 during the analysis, was 1.3.

Composite CVD-related hospitalization risk rose from 2.6% with exposures of less than or equal to 5.0 µg m-3 to 3.4% with exposures ranging from 9.0 to 10 µg m-3.

The effects lasted for ≥3.0 years following PM2.5 exposure. Education, age, healthcare access, and neighborhood socioeconomic deprivation influenced PM2.5 sensitivity.

The highest risk for composite cardiovascular disease and the most common cardiovascular disease CVD subtypes (cerebrovascular disease, ischemic heart disease, and cardiac failure) was related to immediate PM2.5 exposure at lag 0, and a significantly reduced impact at lag 1.0 followed by a decrease at lag 2.0.

Female beneficiaries were more likely to develop composite cardiovascular disease, heart failure, and ischemic heart disease, although cardiomyopathy risk was lower.

Younger beneficiaries and individuals aged between 65 and 74 years are more likely to be admitted to the hospital for CVD and subtypes. Those living in areas with lower high school graduation rates, higher deprivation levels, or longer hospital distances likely experienced the most outcomes.

Conclusion

The study findings showed that chronic exposure to fine-sized particulate matter increases the risk of cerebrovascular illnesses, ischemic heart diseases, cardiomyopathy, heart failure, arrhythmia, and abdominal and thoracic aortic aneurysms.

Exposure-response curves for several CVD subtypes shifted, indicating a lack of a safe threshold for cardiovascular health.

Adhering to the WHO’s air quality standards of ≤5 µg/m3 can provide considerable advantages. Susceptibility varied by participant age, healthcare access, educational achievement, and neighborhood deprivation.

Cardiac arrhythmia and heart failure are among the most vulnerable CVD subtypes in patients exposed to PM2.5.

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February 22, 2024
Fine particulate matter exposure linked to increased hospital admissions for major diseases

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Short and long term exposure to fine particulate matter (PM2.5) air pollution is linked to an increased risk of hospital admission for major heart and lung diseases, find two large US studies, published by The BMJ today.

Together, the results suggest that no safe threshold exists for heart and lung health.

According to the Global Burden of Disease study, exposure to PM2.5 accounts for an estimated 7.6% of total global mortality and 4.2% of global disability adjusted life years (a measure of years lived in good health).

In light of this extensive evidence, the World Health Organization (WHO) updated the air quality guidelines in 2021, recommending that an annual average PM2.5 levels should not exceed 5 μg/m3 and 24 hour average PM2.5 levels should not exceed 15 μg/m3 on more than 3-4 days each year.

In the first study, researchers linked average daily PM2.5 levels to residential zip codes for nearly 60 million US adults (84% white, 55% women) aged 65 and over from 2000 to 2016. They then used Medicare insurance data to track hospital admissions over an average of eight years.

After accounting for a range of economic, health and social factors, average PM2.5 exposure over three years was associated with increased risks of first hospital admissions for seven major types of cardiovascular disease – ischemic heart disease, cerebrovascular disease, heart failure, cardiomyopathy, arrhythmia, valvular heart disease, and thoracic and abdominal aortic aneurysms.

Compared with exposures of 5 μg/m3 or less (the WHO air quality guideline for annual PM2.5), exposures between 9 and 10 μg/m3, which encompassed the US national average of 9.7 μg/m3 during the study period, were associated with a 29% increased risk of hospital admission for cardiovascular disease.

On an absolute scale, the risk of hospital admission for cardiovascular disease increased from 2.59% with exposures of 5 μg/m3 or less to 3.35% at exposures between 9 and 10 μg/m3. “This means that if we were able to manage to reduce annual PM2.5 below 5 µg/m3, we could avoid 23% in hospital admissions for cardiovascular disease,” say the researchers.

These cardiovascular effects persisted for at least three years after exposure to PM2.5, and susceptibility varied by age, education, access to healthcare services, and area deprivation level.

The researchers say their findings suggest that no safe threshold exists for the chronic effect of PM2.5 on overall cardiovascular health, and that substantial benefits could be attained through adherence to the WHO air quality guideline.

“On February 7, 2024, the US Environmental Protection Agency (EPA) updated the national air quality standard for annual PM2.5 level, setting a stricter limit at no more than 9 µg/m3. This is the first update since 2012. However, it is still considerably higher than the 5 µg/m3 set by WHO. Obviously, the newly published national standard was not sufficient for the protection of public health,” they add.*

In the second study, researchers used county-level daily PM2.5 concentrations and medical claims data to track hospital admissions and emergency department visits for natural causes, cardiovascular disease, and respiratory disease for 50 million US adults aged 18 and over from 2010 to 2016.

During the study period, more than 10 million hospital admissions and 24 million emergency department visits were recorded.

They found that short term exposure to PM2.5, even at concentrations below the new WHO air quality guideline limit, was statistically significantly associated with higher rates of hospital admissions for natural causes, cardiovascular disease and respiratory disease, as well as emergency department visits for respiratory disease.

For example, on days when daily PM2.5 levels were below the new WHO air quality guideline limit of 15 μg/m3, an increase of 10 μg/m3 in PM2.5 was associated with 1.87 extra hospital admissions per million adults aged 18 and over per day.

The researchers say their findings constitute an important contribution to the debate about the revision of air quality limits, guidelines, and standards.

Both research teams acknowledge several limitations such as possible misclassification of exposure and point out that other unmeasured factors may have affected their results. What’s more, the findings may not apply to individuals without medical insurance, children and adolescents, and those living outside the US.

However, taken together, these new results provide valuable reference for future national air pollution standards.

Source:

Journal reference:

Wei, Y., et al. (2024) Exposure-response associations between chronic exposure to fine particulate matter and risks of hospital admission for major cardiovascular diseases: population based cohort study. BMJ. doi.org/10.1136/bmj-2023-076939.

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February 22, 2024
Study links ultra-processed food consumption with higher cardiovascular risk
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In a recent study published in the journal EClinicalMedicine, a team of Chinese researchers conducted a systematic review and meta-analysis to understand the dose-response relationship between increased consumption of ultra-processed foods and the risk of cardiovascular events.

Study: Ultra-processed food consumption and risk of cardiovascular events: a systematic review and dose-response meta-analysis

Background

Diet is considered one of the major modifiable risk factors of cardiovascular disease, which continues to be a serious public health concern and the leading cause of death. Furthermore, despite strong evidence for and various guidelines recommending whole grains and unprocessed foods for heart health, the growing food processing industry and the fast-paced nature of modern lifestyles have increased the dependence on and consumption of ultra-processed foods.

Ultra-processed foods are made using ingredients already processed to a large extent and contain synthetic food additives such as preservatives, food colors, and stabilizers. The consumption of ultra-processed foods is also known to differ across age groups and countries, with younger individuals in the United States having the highest consumption of ultra-processed foods. Increased intake of ultra-processed foods, which include foods and beverages with added sugars, refined grains, and processed meats, also results in significant non-adherence to the Mediterranean diet, which has been recommended for cardiovascular health.

About the study

In the present study, the researchers investigated the dose-response relationship between the consumption of ultra-processed foods and the risk of cardiovascular events by conducting a systematic review and meta-analysis of observational studies on the association between ultra-processed food consumption and cardiovascular events such as coronary heart disease and cerebrovascular disease.

The review did not include any animal model studies; only those published in English were considered. Furthermore, all case-control, cohort, and cross-sectional observational studies that included participants above the age of 18 years, with ultra-processed food consumption as the examined exposures, were included in the review.

The included studies were also required to follow the Nova food classification system, with examined outcomes being cardiovascular events such as stroke, myocardial infarction, coronary intervention such as stent thrombosis, transient ischemic attack, peripheral vascular intervention, acute heart failure, hospitalization due to angina, or mortality due cardiovascular disease. Studies that did not have effect estimates in the form of hazard ratios or odds ratios were excluded.

Data extracted for the meta-analysis included the tools used for dietary assessments, the number of years of follow-up, outcomes and how they were defined, the covariates that were considered during the multivariate analyses, and effect size and evaluation criteria for ultra-processed food consumption.

The extracted data were used to conduct a meta-analysis and dose-response examination using different units of consumption of ultra-processed foods such as weight, energy proportion, and servings. A stratified analysis was also carried out to evaluate the outcomes of cardiovascular events and cerebrovascular disease, adjusted for factors such as country of study, dietary quality, method of dietary assessment, publication year, duration of follow-up, and sample size. The relative risk of cardiovascular events was also estimated for each unit increase in ultra-processed food consumption.

Results

The study found that consumption of ultra-processed foods had a linear relationship with increasing risk of cardiovascular events. Furthermore, daily consumption of ultra-processed foods measured in terms of energy proportion and serving showed a positive correlation with coronary heart disease. However, the risk of cerebrovascular disease was not found to be associated with the consumption of ultra-processed foods.

A 10% increase in weight proportion of daily consumption of ultra-processed foods was found to increase the risk of cardiovascular events by 1.9%, and an extra serving of ultra-processed food was found to increase cardiovascular event risk by 2.2%. Similarly, a 10% increase in terms of energy proportion in the daily intake of ultra-processed foods corresponded to a 1.6% increase in the risk of cardiovascular events.

The meta-analysis included over a million cases, of which more than 50,000 were of cardiovascular events. Given the large sample size, which covered data from 22 cohorts, the scientists believe that the findings were well supported. The review also included numerous studies that reported no or opposite associations between ultra-processed food consumption and the risk of cardiovascular events, decreasing the bias risk in the meta-analysis findings.

Conclusions

Overall, the findings highlight the detrimental effects of ultra-processed foods in increasing the risk of cardiovascular disease. Furthermore, the dose-response analysis indicated an increase in cardiovascular event risk based on increased ultra-processed food consumption in terms of energy proportion, weight, and servings. These results emphasize the need for more public health initiatives to educate people about the increasing risk of cardiovascular disease due to unhealthy diets.
Journal reference:

Qu, Y., Hu, W., Huang, J., Tan, B., Ma, F., Xing, C., & Yuan, L. (2024). Ultra-processed food consumption and risk of cardiovascular events: a systematic review and dose-response meta-analysis. EClinicalMedicine, 69. DOI: 10.1016/j.eclinm.2024.102484, https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(24)00063-4/fulltext
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February 22, 2024
Women gain more health benefits from exercise than men
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In a recent study published in the Journal of the American College of Cardiology, researchers investigated the sex-specific all-cause and cardiovascular mortality risk reductions derived from physical activity. They used a large (n = 412,313) cohort American cohort to identify this association and found that women derived greater benefits than their male counterparts from equivalent amounts of physical activity.

Historically, however, women have generally lagged men in exercise engagement. These findings may help inform clinicians and the health-minded of the advantages of physical exercise in combatting chronic cardiovascular disease (CVD) and bridge observed “gender gaps” by encouraging women to take up leisure-time physical activity.

Study: Sex Differences in Association of Physical Activity With All-Cause and Cardiovascular Mortality.

The gender gap and what this means for sex-specific cardiac health

Cardiovascular mortality remains one of the leading causes of global human loss of life, alarmingly a likely underestimation when considering that cardiovascular disease (CVD) is a commonly reported comorbidity in numerous non-transmissible and transmissible pathologies. Decades of research have revealed that physical activity (PA) can substantially reduce all-cause and cardiovascular mortality, but records reveal that public involvement in leisure time PA is sorely lacking.

In the United States of America (US) alone, fewer than 25% of citizens meet the minimum PA recommendations of 150 min/wk. of moderate PA or 75 min/wk. of vigorous PA prescribed by the US Centers for Disease Control and Prevention (CDC) and the American College of Cardiology. Significant inter-sex differences in PA engagement further skew these already suboptimal observations – a substantially larger proportion of men are known to engage in leisuretime PA than women, which, when combined with differences in physiological responses, exercise capacities, and activity tolerances between the sexes, might result in significantly different mortality outcomes between these cohorts.

Unfortunately, the empirical outcomes of these “gender gaps” between men and women have never been tested within a scientific framework, denying clinicians, policymakers, and the health conscious of the information they need to optimize PA-related outcomes. Understanding the role of sex in these associations would allow for improved guidelines aimed at bridging the gender gap, fostering increased female PA engagement, and reducing overall mortality risk.

About the study

In the present study, researchers aimed to elucidate if PA-derived health benefits differ depending on the sex of the PA-engaging individual. Their cohort was derived from the National Health Interview Survey (NHIS), a large-scale collaboratory effort carried out by the CDC and the National Center for Health Statistics. Established in 1957, the NHIS is a prospective cohort maintaining health records of Americans across 50 states and the District of Columbia, representing a proxy for America’s health.

The current study used participant data from 1997 to 2017 and was initially comprised of 646,279 individuals. Excluding participants with severe cardiovascular conditions (e.g., coronary heart disease), cancers, or missing demographic or medical data resulted in a final cohort of 412,413 adults. Data collection included demographic and medical information (from the NHIS database) and a consistent, standardized questionnaire for PA frequency, duration, and type assessment, presented at both baseline and follow-up evaluations.

Cox proportional hazard regression models corrected from demographic and clinical covariates were used to assess primary outcomes. Likelihood ratio tests were used to compute sex-specific differences in outcome estimates.

Study findings

Demographic data collation revealed that 54.7% of included participants were women, more than 68% of whom were of White ethnicity. The average age of the study cohort was 43.9 years, and the study collected a total of 4,911,178 person-years of follow-up data. During the course of the study, 39,935 participants died from all causes, 11,670 of which were cardiovascular.

Previously observed discrepancies in sex-specific PA engagement were validated in this study, with only 32.5% of women engaging in weekly aerobic PA compared to 43.1% of male participants. Every PA metric measured in the survey revealed greater male engagement than female, with 15.2% of men achieving the prescription weekly PA goal of 150 min/wk. In contrast, only 10.3% of women met this goal.

However, hazard analyses present that the few women who do engage in physical activity derive far greater relative health benefits than their male counterparts. Compared to inactivity, female PA engagement results in a 24% risk reduction (all-cause mortality), while equivalent PA engagement in men only decreased their mortality risk by 15%.

“In dose-dependent analyses for the entire cohort, the benefit of PA on all-cause mortality peaked at ∼300 min/wk of MVPA and then plateaued. The greatest mortality benefit in men was achieved at 300 min/wk of MVPA with an 18% lower hazard in all-cause mortality. Women derived a similar magnitude of benefit at 140 min/wk of MVPA, and continued to benefit with increasing min/wk of MVPA until the greatest benefit of 24% lower hazard (HR: 0.76; 95% CI: 0.72-0.80) was achieved at ∼300 min/wk.”

While these findings do require validation in non-American cohorts, where observed results, especially those pertaining to engagement, might vary drastically from those observed herein, this study highlights the profound benefits of PA engagement for both sexes and may play a crucial role in motivating traditionally hesitant women to take up these activities given the health rewards they provide.
Journal reference:

Ji, H., Gulati, M., Huang, T. Y., Kwan, A. C., Ouyang, D., Ebinger, J. E., Casaletto, K., Moreau, K. L., Skali, H., & Cheng, S. (2024). Sex Differences in Association of Physical Activity With All-Cause and Cardiovascular Mortality. Journal of the American College of Cardiology, 83(8), 783-793, DOI – 10.1016/j.jacc.2023.12.019, https://www.sciencedirect.com/science/article/pii/S0735109723083134?via%3Dihub
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February 21, 2024