Genes responsible for premature ovarian insufficiency questioned by researchers

6th July 2023

Premature ovarian insufficiency (POI) in the majority of women is not due to autosomal dominant variants in genes, according to a recent analysis.

Published in the journal Nature Medicine, researchers set out to systematically evaluate the penetrance of purported pathogenic gene variants using exome sequence data in women with POI.

They considered 67 genes used in the Genomics England diagnostic gene panel for POI, and identified an additional 38 genes from additional literature.

The team used exome sequence data in 104,733 women from the UK Biobank, 2,231 of whom (1.14%) reported natural menopause under the age of 40 years.

The analysis showed limited evidence to support any previously reported autosomal dominant effect. In fact, for nearly all heterozygous effects on previously reported POI genes, researchers were able to rule out even modest penetrance. For instance, 99.9% of all protein-truncating variants were present in reproductively healthy women.

Taken together, these results suggest that in the vast majority of women, POI is not actually caused by autosomal dominant variants either in genes previously reported or currently evaluated in clinical diagnostic panels.

In other words, while there are specific genetic variants in women who experience premature menopause, it is unlikely that these variants are the underlying cause, since many are also found in those who experience a normal age menopause.

POI in context

POI affects an estimated 1% of the general population and results in cessation of ovarian function before the age of 40 years. Moreover, women with POI find that menstruation also stops around the same age. In recent years, it has become clear that POI is likely to have a genetic basis and although several candidate genes have been identified, it appears that POI is a genetically heterogeneous condition.

Healthy sleep pattern could help reduce risk of developing asthma

13th April 2023

A healthy sleep pattern could reduce the risk of adults developing asthma even among those with a high genetic susceptibility to the disease

According to Chinese researchers and based on an analysis of individuals in the UK Biobank, having a healthy sleep pattern appears to mitigate the effect of genetic susceptibility to asthma.

Asthma is a chronic respiratory inflammatory disease and which globally, has been estimated to affect between 9.8 and 17.9% of the population depending on whether the definition includes wheezing or ever wheeze. Although there are a number of potential causes of asthma including a family history and exposure to various allergens, the presence of a persistent short sleep duration is one factor identified as being associated with an increased risk of developing asthma. While genome-wide association studies have revealed some asthma loci, the variability of genetic influence suggests that several other, non-genetic exposures may also influence the development of asthma.

In the current study, researchers examined the association between sleep traits, genetic susceptibility and the risk of asthma in a UK Biobank cohort. The team undertook an analysis of those aged 38-73 years and for whom polygenic risk scores and comprehensive sleep scores, were constructed. The researchers used a multivariable Cox proportional hazard regression model to investigate the independent and combined effects of sleep pattern and genetic susceptibility on asthma incidence. Participants were assigned as being at a low, intermediate and high risk of asthma based on genetic susceptibility and sleep categorised as ‘healthy’, ‘intermediate’ and ‘poor’.

Healthy sleep pattern and development of asthma

From a total of 455,405 individuals with a mean age of 56.5 years (54% female), 17,836 were diagnosed with asthma during over 10 years of follow-up. 

Compared with those deemed to be a low genetic risk, the hazard ratio (HR) for those with the highest genetic risk was 1.47 (95% CI 1.41 – 1.52) for the development of asthma. Similarly, among those with poor sleep, there was also an elevated risk for asthma (HR = 1.55, 95% CI 1.45 – 1.65). In addition, among those with a high genetic risk and categorised as having poor sleep, there was a more than two-fold increased risk of developing asthma (HR = 2.22, 95% CI 1.97 – 2.49, p < 0.001).

However, in further analysis, researchers found that a healthy sleep pattern was associated with a lower risk of asthma in all three genetic susceptibility groups. For example, a healthy sleep pattern reduced the risk of developing asthma by 44% (HR = 0.56) among those at a low genetic risk and by 37% in those at high genetic risk (HR = 0.63). In fact, the researchers calculated that at the population level, a low genetic risk and a healthy sleep pattern could reduce the risk of asthma cases by up to 19%.

The authors concluded that a healthy sleep pattern reflected a lower risk of asthma in adult populations and could be beneficial to asthma prevention regardless of genetic conditions.

Citation
Xiang B et al. Highlighting the importance of healthy sleep patterns in the risk of adult asthma under the combined effects of genetic susceptibility: a large-scale prospective cohort study of 455 405 participants. BMJ Open Respir Res 2023

Ketogenic diet linked to higher LDL cholesterol and increased risk of adverse cardiac events

16th March 2023

A ketogenic diet was found to be associated with increased levels of LDL cholesterol and double the risk of an adverse cardiovascular event.

In a study presented at the American College of Cardiology (ACC) Scientific Session/World Congress of Cardiology (WCC) 2023, researchers described how following a ketogenic diet, involving consumption of very low amounts of carbohydrates and high amounts of fats, appeared to increase levels of LDL cholesterol and the risk of an adverse cardiovascular event.

A ketogenic diet, also referred to as a low carbohydrate, high fat (LCHF) diet, contains high amounts of fat (55-60%), 30-35% protein and 5-10% carbohydrate.

Overall, it seems that a ketogenic diet plays appears to play a significant therapeutic role in various cardiometabolic diseases and there is certainly evidence of a benefit when used as an intervention for overweight patients with type 2 diabetes.

However, despite these advantages, others have raised concerns that a ketogenic diet has the potential to exacerbate or cause hypercholesterolaemia in patients with or without underlying genetic hyperlipidaemia.

Nevertheless, whether a ketogenic diet over time gives rise to adverse cardiovascular events is unclear given the absence of long-term data.

The study presented at ACC/WCC tried to answer this question and researchers used information from data held in the UK Biobank and identified individuals meeting their their definition of a ketogenic diet diet, i.e. no more than 25% of total daily calories from carbohydrates and more than 45% from fat. 

These individuals were then matched to a group who self-reported eating a normal diet.

The main outcome of the study was the effect of a ketogenic diet on serum lipids whereas a secondary outcome was the composite incidence of adverse cardiovascular events (e.g., angina, myocardial infarction, coronary artery disease, ischaemic stroke, peripheral arterial disease, or coronary/carotid revascularisation.)

Ketogenic diet outcomes

A total of 305 participants eating a ketogenic diet diet were matched with 1,220 eating a standard diet. The mean age of the sample was 54, some 73% were women and the mean body mass index (BMI) of 27.7 compared to 26.7 on the standard diet.

After an average follow-up of 11.8 years, a ketogenic diet gave rise to higher LDL cholesterol levels compared to a standard diet (3.80 vs 3.64 mmol/L, p = 0.004). There was also a significantly higher level of apolipoprotein B (1.09 vs 1.04 g/L, p < 0.001).

However, after adjustment for cardiovascular risk factors, such as diabetes, hypertension, obesity and smoking, researchers found that 9.8% of those on a ketogenic diet and 4.3% on a standard diet experienced an adverse cardiovascular event (adjusted hazard ratio, aHR = 2.18, 95% CI 1.39 – 3.43, p < 0.001).

Despite these findings, the authors did acknowledge the limitations of their study in that the information was self-reported and based on a single time-point. They also noted how not everyone responds to a ketogenic diet in the same way.

Source
‘Keto-Like’ Diet May Be Linked to Higher Risk of Heart Disease, Cardiac Events. ACC Anywhere.

Drinking coffee and tea significantly reduces cardiovascular disease mortality

9th January 2023

Drinking both coffee and tea is significantly associated with a significantly reduced risk of cardiovascular disease and all-cause mortality

A large prospective study by Chinese researchers has found that both separately and combined, coffee and tea consumption is inversely associated with a reduced cardiovascular disease (CVD) and all-cause mortality, highlighting the potential importance of incorporating both into an individual’s diet, provided that these observed associations are causal. 

Long-term and moderate consumption of coffee is known to be significantly and inversely associated with cardiovascular disease risk, with the greatest reduction seen with 3 to 5 cups per day. In addition, evidence from China also suggests that daily green tea consumption is associated with a lower risk of incident type 2 diabetes and a lower risk of all-cause mortality in diabetics though the associations for other types of tea is less clear. Nevertheless, emerging data suggests that higher green tea and coffee consumption is inversely associated with a lower risk of cardiovascular disease and stroke in the general population. To date, however, only one study has examined the mortality benefit from coffee and tea consumption, finding that higher consumption of both was associated with reduced all-cause mortality, although the study was restricted to patients with type 2 diabetes. Consequently, it remains unclear whether the benefits of consuming both drinks are more generalisable. In the present study, the Chinese researchers aimed to examine the separate and combined associations of consuming the two beverages, with total and cause-specific mortality (including cardiovascular disease, CVD, respiratory and digestive disease using data from a population-based longitudinal cohort of individuals registered with the UK Biobank.

Intake of coffee and tea were assessed at baseline using a self-reported questionnaire but the researchers also collected information on a range of factors including age, gender, sociodemographic, behavioural (e.g., smoking, exercise, alcohol intake and dietary intake). Intake of both drinks categorised as coffee: none, < 1–2, 3–4 and ≥ 5 cups/day and tea: none, < 1–1, 2–4 and ≥ 5 cups/day. 

Coffee and tea intake and mortality outcomes

A total of 498,158 participants with a median age of 58 years (54% female) were included in the analysis. These individuals were followed up for a median of 12.1 years, during which time 34,699 deaths were identified.

In a separate analysis and after adjusting for potential confounders, drinking less than 1 – 2 cups/day of coffee, was inversely associated with a lower risk of all the health outcomes assessed. For example, a 9% lower risk for all-cause mortality (hazard ratio, HR = 0.91, 95% CI 0.88–0.93)and a 6% reduced risk for cardiovascular mortality (HR = 0.94, 95% CI 0.88–1.00). Among those drinking tea, 2 – 4 cups/day was associated with a lower risk for all-cause (HR = 0.86, 95% CI 0.83–0.88) as well as CVD mortality (HR = 0.88 95% CI 0.81–0.94).

However, in joint analyses and compared to those who did not drink either beverage, the combination of < 1 – 2 cups/day of coffee and 2 – 4 cups/day of tea, significantly lowered all-cause mortality (HR = 0.78 95% CI 0.73-0.85) and CVD mortality (HR = 0.76 95% CI 0.64-0.91). Interestingly, the lowest mortality occurred for gastrointestinal disease from drinking both < 1 – 2 cup/day of coffee and ≥ 5 cups/day of tea (HR = 0.42, 95% CI 0.34-0.53).

The authors concluded that consumption of both drinks were both separately and jointly, inversely associated with all-cause and cause-specific mortality.

Citation
Chen Y et al. Consumption of coffee and tea with all-cause and cause-specific mortality: a prospective cohort study. BMC Med 2022

Fish oil supplement use and atrial fibrillation

7th October 2022

Whether fish oil supplement use affects the risk of incident atrial fibrillation was examined in a large UK prospective cohort study

Fish oil supplement use in patients with cardiovascular disease has been shown to provide a small beneficial advantage in terms of mortality and admission to hospital for cardiovascular reasons in patients with heart failure. However, not all studies with fish oils has have been positive.

For instance, other data in patients with atherogenic dyslipidaemia and high cardiovascular risk, have found that among statin-treated patients at high cardiovascular risk, the addition of omega-3 fatty acids, resulted in no significant difference in a composite outcome of major adverse cardiovascular events when compared with corn oil.

Despite these ambiguous findings with respect to cardiovascular disease, there is some evidence that fish oil supplement use among patients with atrial fibrillation (AF) is beneficial. For example, in one trial among patients with persistent atrial fibrillation on amiodarone and a renin-angiotensin-aldosterone system inhibitor, the addition of fish oil supplementation improved the probability of maintaining sinus rhythm after direct current cardioversion, possibly through prevention of atrial fibrillation recurrence.

In contrast, a recent study with both fish oils and vitamin D supplementation observed that compared with placebo, neither supplement had a significant effect on the risk of incident atrial fibrillation over a follow-up of more than 5 years. But when data has been pooled, one 2021 meta-analysis found that fish oil supplement use was associated with an increased risk of AF which was greater in trials testing >1 g/d.

With some evidence to suggest that both monogenic and polygenic factors contribute to AF risk in the general population, in the present study, a team of Australian researchers sought to examine whether habitual fish oil supplement use was associated with the risk of incident AF after adjustment for several factors including individual’s genetic risk score.

Using the UK Biobank data, individuals were dichotomised (Yes/No) as habitual fish oil users. After calculation of an AF genetic risk score, individuals were categorised to be at either low, immediate or high genetic risk.

The primary outcome of the study was set as incident AF and the researchers also considered the risk of AF in those with and without cardiovascular disease at the study baseline point. The results were adjusted for several factors including age, gender, consumption of oily fish and genetic risk score.

Fish oil supplement use and incident atrial fibrillation

A total of 468,665 individuals with a mean age of 56.5 years (45.2% male) were included in the analysis and followed for a median of 11.1 years.

During the period of follow-up, the risk of developing incident AF was significantly higher among fish oil supplement users (adjusted hazard ratio, aHR = 1.10, 95% CI 1.07 – 1.13, p < 0.0001).

When considering the risk of AF based on genetic risk scores, this was significantly higher for low (HR = 1.08), intermediate (aHR = 1.10) and high risk (aHR = 1.11) fish oil supplement users.

Finally, while there was no increased risk among those with existing cardiovascular disease (CVD), the risk was elevated (aHR = 1.13) among those without CVD at baseline.

The authors concluded that habitual fish oil supplement use was associated with a higher risk of incident atrial fibrillation and that this risk remained regardless of genetic AF risk and consumption of oily fish but was only observed in those without cardiovascular disease.

Citation
Zhang J et al. Habitual fish oil supplementation and the risk of incident atrial fibrillation: findings from a large prospective longitudinal cohort study Eur J Prev Cardiol 2022

Coffee drinking associated with cardiovascular and mortality benefits

6th October 2022

Irrespective of how it is prepared, coffee drinking significantly lowers the risk of incident cardiovascular disease and mortality

Coffee drinking, whether ground, instant or even decaffeinated, appears to lower the risk of incident cardiovascular disease and death according to the findings of a large analysis of data held within the UK Biobank database by Australian researchers.

Caffeine is widely consumed and it has been suggested that intake of tea and coffee, particularly in moderate doses, does not appear to be harmful and may even be beneficial in a range of cardiovascular conditions, including coronary artery disease, heart failure and arrhythmias. Nevertheless, this perception has not always been held within the medical profession. For example, in a 1998 survey of 697 medical specialists which sought to determine consensus on the harmful effects of caffeine, more than 75% recommended a reduction in caffeine in patients with anxiety, arrhythmias, oesophagitis or hiatal hernia, fibrocystic disease, insomnia, palpitations, and tachycardia. In contrast, more recently, evidence points towards a beneficial effect of coffee drinking in that it reduces the risk of coronary heart disease, heart failure, arrhythmia, stroke, CVD and all cause mortality. Whilst there is now a greater acceptance that drinking coffee is associated with health benefits, little is known about how the different methods of preparation e.g., instant, ground etc might impact on cardiovascular outcomes.

In the present study, the Australian team used data from the UK Biobank and categorised coffee drinking into the different subtypes (ground, instant, decaffeinated) and the divided intake as 0, < 1, 1, 2 – 3, 4 – 5 and > 5 cups of coffee/day. Cardiovascular outcomes examined were coronary heart disease, cardiac failure and ischaemic stroke. Using Cox regression modelling, the researchers also assessed the associations with incident arrhythmia, cardiovascular disease and overall mortality and results were adjusted for several factors including age, gender, alcohol intake, co-morbidities. They set the primary outcome as the relationship between coffee subtypes and incident arrhythmias, cardiovascular disease (CVD) and mortality.

Coffee drinking and cardiovascular outcomes

A total of 449,563 individuals with a median age of 58 years (55.3% female) were included in the analysis and followed for 12.5 years. A total of 100,510 served as non-drinking coffee controls.

All coffee subtypes were associated with a reduced risk of cardiovascular outcomes and the greatest reduction in risk occurred among those drinking 2 – 3 cups/day. For example, the risk of CVD was 10% lower (hazard ratio, HR = 0.90, 95% CI 0.87 – 0.92, p < 0.0001), 16% lower for ischaemic stroke (HR = 0.84) and 17% lower for cardiovascular mortality (HR = 0.83) with all reductions being statistically significant. Furthermore, the incidence of cardiac arrhythmias was also lowest among those drinking 2 – 3 cups/day.

When considering the different coffee subtypes, the greatest reductions were again observed for those drinking 2 – 3 cups/day and were significant for decaffeinated, instant and ground. However, there was no significant reduction in the risk of arrhythmia among those drinking decaffeinated coffee and in fact, there was a 14% higher risk of any arrhythmia in those drinking < 1 cup/day (HR = 1.14, 95% CI 1.04 – 1.26, p = 0.0068).

The authors concluded that consumption of 2 – 3 cups/day of any form of coffee reduced the risk of incident cardiovascular disease, arrhythmias and mortality. However, drinking decaffeinated coffee did not impact on the risk of arrhythmias and the authors added that mild to moderate coffee intake of all types should be considered as part of a healthy lifestyle.

Citation

Chieng D et al. The impact of coffee subtypes on incident cardiovascular disease, arrhythmias, and mortality: long-term outcomes from the UK Biobank Eur J Prev Cardiol 2022

Should daily coffee intake be part of a healthy diet?

11th April 2022

Studies have shown that daily coffee intake is associated with cardiovascular benefits such as a lower risk of developing CVD and arrhythmias

Coffee intake (whether ground or instant) of at least 2 – 3 cups per day has been found to be associated with significant reductions in the risk of developing cardiovascular disease (CVD), arrhythmias, as well as cardiovascular and all-cause mortality. This is according to the findings of three studies analysing data held within the UK Biobank.

Although coffee contains caffeine, it is also a rich source of phenolic compounds including chlorogenic acids which contribute to coffee’s antioxidant activity. Moreover, coffee intake at midlife has been associated with a lower risk of dementia and Alzheimer’s disease compared with those drinking no or only little coffee.

However, the cardiovascular benefits from drinking coffee are less clear with one study finding that in men, the risk of nonfatal myocardial infarction was not associated with coffee drinking.

In contrast, a large prospective study observed that coffee consumption was inversely associated with total and cause-specific mortality.

Due to these conflicting results, three studies presented at the American College of Cardiology Scientific Session have examined cardiovascular and mortality benefits disease associated with coffee intake.

In the first study, effects of habitual coffee consumption on incident cardiovascular disease, arrhythmia, and mortality: findings from UK BIOBANK, researchers from the University of Melbourne, Australia, included data from 382,535 individuals with a mean age of 57 years (52% female) and assessed the effect of coffee intake over a 10-year period.

The results showed that a coffee intake of 2 – 3 cups/day was significantly associated (for all associations, p < 0.01) with the lowest risk for developing CVD (Hazard ratio, HR = 0.91, 95% CI 0.88 – 0.94), coronary heart disease (HR = 0.90), heart failure (HR = 0.85) and all-cause mortality (HR = 0.86).

They found a U-shaped relationship between higher coffee intake and incident arrhythmia which was also lowest at 2 – 3 cups/day (HR = 0.92).

In the second study, regular coffee intake is associated with improved mortality in prevalent cardiovascular disease, the Australian team focused on the effect of coffee in patients with existing cardiovascular disease.

With a population of 502,543 individuals, again followed for 10 years, CVD was subsequently diagnosed in 342,279 participants, of whom, 19.6% died. The team found that coffee intake was safe at all levels and that survival was improved again at 2 – 3 cups/day (HR = 0.92, 95% CI 0.86 – 0.99, p = 0.03).

Among 24,111 participants diagnosed with an arrhythmia, drinking only one cup of coffee per day was associated with the lowest mortality risk (HR = 0.85) and specifically in those with atrial fibrillation or flutter, one cup of coffee per day was associated with improved survival (HR = 0.82, p < 0.01).

In the third study, ground, instant or decaffeinated coffee? Impact of different coffee subtypes on incident arrhythmia, cardiovascular disease and mortality, the team wondered if there were any differential cardiovascular benefits depending on how the coffee was prepared. Overall, they found that drinking between 1 and 5 cups of coffee per day were associated with a reduced risk of arrhythmia, CVD, CHD, heart failure and stroke.

The greatest reduction in risk for CVD was seen with drinking 2 – 3 cups/day of ground coffee (HR = 0.83, 95% CI 0.79 – 0.87) but there was still a significant, albeit smaller, reduction in risk from consuming instant coffee (HR = 0.91, 95% CI 0.88 – 0.95).

Finally, in the third study, the authors showed that drinking 2 – 3 cups/day of decaffeinated coffee was associated with a mortality benefit (HR = 0.85, 95% CI 0.80 – 0.91, p < 0.01), leading the authors to conclude that non-caffeine compounds within coffee are likely to be important factors associated with greater survival among coffee drinkers.

Given these findings, the authors suggested that coffee intake should be considered as part of a healthy diet.

Prospective analysis shows regular meat eaters at higher risk of several types of cancer

21st March 2022

A UK study has found that meat eaters have an increased risk of developing cancer compared with either low meat eaters, pescatarians or vegetarians

Individuals who are regular meat eaters have been found to be at a higher risk of all and some specific cancers compared to those who are either low meat eaters, pescatarians or vegetarians. This was the finding of a study of the UK Biobank database by researchers from the Cancer Epidemiology Unit, University of Oxford, Oxford, UK.

Cancer has been declared by the World Health Organization (WHO) as a leading cause of death worldwide accounting for nearly one in six of all deaths (10 million in 2020). Moreover, according to WHO, breast, lung, colorectal and prostate cancers are the most common forms of the disease.

Understanding the causal relationship between dietary patterns or even particular dietary components and cancer aetiology and prevention is a challenge.

For example, undertaking randomised controlled intervention trials to examine the association between diet and cancer outcomes are not feasible, for a number of reasons including cost, the difficulty of ensuring compliance among control and intervention groups as well as the long time-frame and exposure necessary to affect the carcinogenesis process.

Although it has been shown that the risk of some cancers is lower in fish eaters and vegetarians than in meat eaters, it is not universally true with other work showing no statistically significant associations with dietary pattern and risk of premenopausal breast cancer.

For the present analysis, the Oxford team examined the relationship between those who ate meat at least 5 times a week, low meat consumers (< 5 times/week), pescatarians and vegetarians and the risk of all cancers and in particular, colorectal, postmenopausal breast and prostate cancers.

They used data held in the UK Biobank and excluded individuals with a cancer diagnosis at recruitment. Participants completed an online questionnaire at recruitment into the database which asked about consumption and frequency of meat intake.

The team also assessed whether specific hormones such as insulin-like growth factor-1 and testosterone as well as body mass index, might have potential mediator effects on the association between dietary patterns and cancer risk. The risks for the development of all and any of the specific cancers, were assessed using meat eaters as the reference group.

Meat eaters and cancer risk

A total of 247,571 individuals with a mean age of 56 years (46.4% female) were classed as meat eaters, 205,385 as low-meat eaters, 10,696 as pescatarians and 8,685 as vegetarians. After an average follow-up of 11.4 years, 54,861 incidence cases of cancer occurred; 5882 colorectal, 7537 women with postmenopausal breast cancer, 9501 men with prostate cancer.

After adjustment for several factors such as smoking status, physical activity etc, a vegetarian diet was associated with a 14% lower risk of all cancers compared to the reference group. (hazard ratio, HR = 0.86, 95% CI 0.80 – 0.93). This risk was also significantly reduced for breast cancer (HR = 0.82) and prostate cancer (HR = 0.69).

For pescatarians, there was also a lower risk of all cancers (HR = 0.90) compared to the reference meat group and for prostate cancer (HR = 0.80). For those categorised as low-meat eaters, the risks were only significantly lower for colorectal cancer (HR = 0.91).

After adjustment for possible mediators, only body mass index was found to be relevant and the risk of all cancers was slightly attenuated for vegetarians (HR = 0.88) and pescatarians (HR = 0.92) but remained significant.

Furthermore, the reduced cancer risk remained significant among pescatarians and vegetarians but only for prostate cancer.

The authors concluded that being a pescatarian or vegetarian was associated with a lower risk of all cancers and that this might be attributable to differences in dietary factors in comparison to those who regularly eat meat.

However, they added that it was unclear if these associations are causal or due to residual confounding, i.e., due to other, but unmeasured factors.

Citation
Watling CZ et al. Risk of cancer in regular and low meat-eaters, fish-eaters, and vegetarians: a prospective analysis of UK Biobank participants BMC Med 2022

Higher intake of raw but not cooked vegetables linked to lower CVD risk

1st March 2022

A higher intake of raw but not cooked vegetables appears to be associated with a lower incidence of cardiovascular disease

A higher intake of raw rather than cooked vegetables appears to be linked with a lower incidence of cardiovascular disease (CVD) although this difference might be due to residual confounding. This was the conclusion of a study of patients in the UK Biobank by researchers from the Nuffield Department of Population Health, University of Oxford, Oxford, UK.

The potential health benefits associated with an increased intake of fruit and vegetables has been widely reported for many years. In a 2019 systematic review of studies, the authors noted that the strongest (probable) evidence for increased vegetable intake was for cardiovascular disease protection although there was possible evidence for a reduced risk of colon cancer, depression and pancreatic diseases for fruit intake.

These findings were echoed in a 2020 review which reported that current evidence suggests that fruit and vegetable have the strongest effects in relation to prevention of CVDs. Moreover, another study has found that in 2017, 11 million deaths were attributable to dietary risk factors, including 2 million due to a low intake of fruits. In relation to vegetables, there is little data on the relative benefits of eating either raw (e.g., in salads) or cooked vegetables.

For the present study, the Oxford team used the UK Biobank database to examine the effect of vegetable intake and specifically, the independent effect of raw and cooked vegetables. Within the database, information was collected on the total daily intake of both both uncooked and cooked vegetables.

Participants were asked ‘on average how many heaped tablespoons of salad or raw vegetables would you eat per day‘? and the same question but asking specifically about cooked vegetables. The quantities were then categorised as 0, 1 – 2, 3 – 4, and > 5 for raw/cooked vegetables and 0 – 1, 2 – 3, 4 – 7 and > 8 for total vegetable intake. The researcher also collected demographic, co-morbidity and lifestyle factors such as smoking status, amounts of physical exercise etc which were adjusted for in regression models.

The primary outcomes were CVD incidence and mortality with secondary outcomes of myocardial infarction, incident stroke and all-cause mortality.

Higher intake of vegetables and CVD risk

A total of 399,586 participants with a mean age of 56.1 years (55.4% female) were included in the analysis and during a median follow-up of 12.1 years, there were 18,052 cases of CVD.

Compared to those consuming the lowest total vegetable intake, participating consuming the highest intake had a 10% lower incidence of CVD (hazard ratio, HR = 0.90, 95% CI 0.83 – 0.97). When separating raw and cooked vegetables, the results were also significant, e.g., for raw vegetables the HR was 0.79 and 0.77 for cooked vegetables.

However, when the models were adjusted for covariates, much of the benefits from raw vegetable intake on CVD incidence were attenuated (HR changing from 0.79 to 0.89) although the result remained significant. In contrast, the association with cooked vegetables was completely attenuated (HR = 1.0, 95% CI 0.91 – 1.09).

Based on these findings, the authors concluded that a higher intake of raw but not cooked vegetables was associated with a lower risk of CVD. Nevertheless, they added a caveat that residual confounding was a likely explanation for much, if not all of the observed associations. In other words, it was possible that there were other, unaccounted for variables, not adjusted for in their models, which might have been important.

As such, this means that the results of the study can only demonstrate an association, rather than a causal relationship between intake of raw and cooked vegetables and the risk of incident CVD.

Citation
Feng Q et al. Raw and Cooked Vegetable Consumption and Risk of Cardiovascular Disease: a Study of 400,000 Adults in UK Biobank Front Nutr 2022

Alcoholic spirit intake associated with increased risk of ventricular arrhythmias

23rd December 2021

Only increased alcoholic spirit intake has been found to be associated with a higher risk of ventricular arrhythmias among regular drinkers

Increased alcoholic spirit intake is associated with an increased risk of ventricular arrhythmia but this elevated risk is absent for other forms of alcoholic beverages. This was a key finding from a retrospective analysis by a team from the Centre for Heart Rhythm Disorders, University of Adelaide and Royal Adelaide Hospital, Australia.

Higher intakes of alcohol are generally considered to damage the cardiovascular system although light to moderate alcohol intake appears to be protective. The term ‘holiday heart syndrome‘ has been coined to describe any alcohol-induced atrial arrhythmias and/or conduction disturbance associated with heavy consumption in a person without other clinical evidence of heart disease. Whilst the relationship between atrial arrhythmias and alcohol has become well recognised, there is a paucity of data linking alcohol intake with ventricular arrhythmias (VA). In fact, the available evidence is inconsistent, with some data showing a non-significant association whereas other studies suggesting that heavy alcohol consumption is an important contributing factor. Moreover, the influence of the type of alcoholic drink on VA or even sudden cardiac death (SCD) is also uncertain.

For the present study, researchers used information held in the UK Biobank which provides data on approximately half a million community-dwelling individuals aged 40 to 69 years across the UK. For their analysis, the researchers focused on incident cases of VA but excluded those with a previous history of the condition and former drinkers. The amount of alcohol intake was reported in terms of a standard drink, defined as 8g of alcohol and the average number of standard drinks consumed per week. For alcohol intake, the team also considered the type of each beverage consumed and created regression models which adjusted for several covariates such as age, sex, race, education.

Findings

Data for a total of 408,712 individuals with an average age of 58.3 years (52.1% female) were included in the analysis and who were followed up for a median duration of 11.5 years. The median alcohol intake for the whole cohort was 8 drinks per week although 5.5% of the group reported having never consumed alcohol.

There were a total of 1733 incident VA events and 2044 SCDs which occurred during the follow-up period. Overall, there was no statistically significant association between total alcohol intake and the risk of VA. However, when considered by type of alcoholic beverage, only alcoholic spirit intake was linearly linked with an increased risk of VA among those consuming greater than 14 drinks per week (hazard ratio, HR = 1.15, 95% CI 0.98 – 1.34) and this became statistically significant with more than 28 drinks per week (HR = 1.33, 95% CI 1.03 – 1.73).

For SCD there was a U-shaped distribution of risk with the lowest risk at around 7 drinks per week.

The authors concluded that they were unable to find an association between total intake of beer, cider and wine and VA and that only increased alcoholic spirit intake was linked to a higher risk. In fact, wine intake was associated with a lower risk of SCD although the authors suggested that these findings require clarification from experimental studies.

Citation

Tu SJ et al. Alcohol consumption and risk of ventricular arrhythmias and sudden cardiac death: An observational study of 408,712 individuals Heart rhythm 2021