“Given these results, it is my belief that all patients with high blood pressure should have an annual flu vaccination,” said first author Daniel Modin research associate of the University of Copenhagen, Denmark. “Vaccination is safe, cheap, readily available, and decreases influenza infection. On top of that, our study suggests that it could also protect against fatal heart attacks and strokes, and deaths from other causes.”

According to previous research, the stress flu infection puts on the body may trigger heart attacks and strokes. Patients with hypertension (high blood pressure) are at raised risk of heart attack and stroke. By stopping flu infection, vaccination could also protect against cardiovascular events, but until now this had not been investigated.

The study used Danish nationwide healthcare registers to identify 608,452 patients aged 18 to 100 years with hypertension during nine consecutive influenza seasons (2007 to 2016). The researchers determined how many patients had received a flu vaccine prior to each season. They then followed patients over each season and tracked how many died. In particular, they recorded death from all causes, death from any cardiovascular cause, and death from heart attack or stroke.

Finally, they analysed the association between receiving a vaccine prior to flu season and the risk of death during flu season. The analysis controlled for patient characteristics that could impact the likelihood of dying such as age, comorbidities, medications, and socioeconomic status.

After adjusting for patient differences, in a given influenza season, vaccination was associated with an 18% relative reduction in the risk of dying from all causes, a 16% relative reduction in the risk of dying from any cardiovascular cause, and a 10% relative reduction in the risk of dying from heart attack or stroke.

Mr Modin said: “We show that influenza vaccination may improve cardiovascular outcomes in patients with hypertension. During the nine flu seasons we studied, vaccine coverage ranged from 26% to 36%, meaning that many patients with high blood pressure were not vaccinated. If you have high blood pressure, it would be worth discussing vaccination with your doctor.”

Regarding how flu and cardiovascular disease might be connected, Mr Modin noted that when the influenza virus infects the body it triggers a strong immune reaction and subsequent inflammation. These responses fight the infection and clear the virus from the body but may increase the risk of having a heart attack or stroke.

He said: “Heart attacks and strokes are caused by the rupture of atherosclerotic plaques in the arteries leading to the heart or the brain. After a rupture, a blood clot forms and cuts off the blood supply. It is thought that the high levels of acute inflammation induced by influenza infection reduce the stability of plaques and make them more likely to rupture.”

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Study author Professor Terence Dwyer of the University of Oxford, UK, said: “While previous research has found connections between smoking and BMI in childhood and adult cardiovascular disease, there was no data for blood pressure or serum cholesterol. In addition, it has not been possible to assess the contributions of BMI and smoking while taking cholesterol and blood pressure into account.”

The study used data from the International Childhood Cardiovascular Cohort (i3C) Consortium. Data was pooled on serum cholesterol, blood pressure, BMI, and smoking from seven child cohorts in the US, Australia, and Finland. Information was collected from 1971 onwards on approximately 40,000 children aged 3 to 19 who were followed up at around age 50 for cardiovascular events leading to hospitalisation (heart attack, stroke, peripheral arterial disease) or all-cause death.

Hazard ratios for cardiovascular events were calculated for each risk factor separately, and for all risk factors simultaneously. The latter analysis estimated how important each risk factor might be when all the others are taken into account.

For cardiovascular events leading to hospitalisation, the associations for risk factors were: 

• BMI: 10% rise — > 20% higher risk of an event.
• Systolic blood pressure: 10% rise — > 40% higher risk of an event.
• Serum cholesterol: 10% rise — > 16% higher risk of an event.
• Adolescent smoking — > 77% higher risk of an event.

In the simultaneous analysis of risk factors, the associations with future risk were reduced, suggesting a shared contribution to risk by each, although the smoking association remained relatively unchanged. The associations for death were very similar to those found for cardiovascular events.

Prof Dwyer said: “The study shows a very strong relationship between standard cardiovascular risk factors in children and the probability of a heart attack or stroke later in life. A meaningful proportion of that risk appears to be laid down in childhood and has a detrimental effect independent of adult risk factor levels. Programmes to prevent heart attacks and strokes should put more emphasis on promoting healthy lifestyles in children.”

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Study author Dr Trine Moholdt of the Norwegian University of Science and Technology, Trondheim, Norway said: “Our findings imply that to get the maximum health benefits of physical activity in terms of protection against premature all-cause and cardiovascular death, you need to continue being physically active. You can also reduce your risk by taking up physical activity later in life, even if you have not been active before.”

The aim of this study was to assess how changes in physical activity over 22 years were related to subsequent death from all causes and from cardiovascular disease. Most studies investigating the relationship between physical activity and longevity have asked participants about their level of physical activity only once, and then followed them for several years. But physical activity is a behaviour that changes in many people, so it is important to investigate how such changes over time relate to the risk of death in the future.

The HUNT study invited all residents of Norway aged 20 and older to participate in 1984-1986, 1995-1997, and 2006-2008. At all three time points, individuals were asked about their frequency and duration of leisure time physical activity. The current study used the data from the first and third surveys.

A total of 23,146 men and women were included in the analysis. Physical activity was categorised as inactive, moderate (less than two hours a week), and high (two or more hours per week). Participants were divided into groups according to their activity levels at each survey.

Physical activity data were linked to information on deaths until the end of 2013 using the Norwegian Cause of Death Registry. The risk of death in each physical activity group was compared to the reference group (those who reported a high level of exercise during both surveys). The analyses were adjusted for factors known to influence prognosis such as body mass index, age, sex, smoking, education level, and blood pressure.

Compared to the reference group, people who were inactive in both 1984-1986 and 2006-2008 had a 2-fold higher likelihood of all-cause death and 2.7-fold greater risk of dying from cardiovascular disease. Those with moderate activity at both time points had 60% and 90% raised risks of all-cause and cardiovascular deaths, respectively, compared to the reference group.

Dr Moholdt noted that there are clear recommendations about the amount of exercise adults should do to optimise their health, which are 150 minutes a week of moderate intensity or 75 minutes a week of vigorous intensity aerobic physical activity.

But she added: “An important point to make here is that physical activity levels even below the advised levels will give health benefits. Physical fitness is more important than the amount of exercise. Clinicians should individualise their advice and help people do even smaller amounts of activity that will improve fitness — this includes all types of exercise that make you breathe heavily.”

“Do activities you like and get more movement into your everyday life,” she continued. “For example, walk to the shops instead of driving, get off the metro a stop early, and use stairs instead of the lift. I recommend everyone to get out of breath at least a couple of times each week.”

As for those who changed categories between surveys, people who went from inactive to highly active had a mortality risk that was between those who were continually active or continually sedentary. In contrast, those who went from highly active to inactive had a similar risk of dying as those who were inactive at both surveys.

“Our data indicate that you can compensate for a previously inactive lifestyle and the sooner you get active, the sooner you will see positive results,” said Dr Moholdt. “My advice is to establish good exercise habits as early in life as possible. The health benefits extend beyond protection against premature death to effects in the body’s organs and on cognitive function. Physical activity helps us live longer and better lives.”

“Nuts are a good source of unsaturated fat and contain little saturated fat,” said study author Dr Noushin Mohammadifard of Isfahan Cardiovascular Research Institute, Iran. “They also have protein, minerals, vitamins, fibre, phytosterols, and polyphenols which benefit heart health. European and US studies have related nuts with cardiovascular protection but there is limited evidence from the Eastern Mediterranean Region.”

This study examined the association between nut consumption and the risk of cardiovascular disease and death in the Iranian population. A total of 5,432 adults aged 35 and older with no history of cardiovascular disease were randomly selected from urban and rural areas of the Isfahan, Arak and Najafabad counties. Intake of nuts including walnuts, almonds, pistachios, hazelnuts, and seeds was assessed in 2001 with a validated food frequency questionnaire.

Participants or family members were interviewed every two years until 2013 for the occurrence of cardiovascular events and death. The specific outcomes investigated were coronary heart disease, stroke, total cardiovascular disease, death from any cause, and death from cardiovascular disease.

During a median 12-year follow-up, there were 751 cardiovascular events (594 coronary heart disease and 157 stroke), 179 cardiovascular deaths, and 458 all-cause deaths.

Eating nuts two or more times per week was associated with a 17% lower risk of cardiovascular mortality compared to consuming nuts once every two weeks. The connection was robust even after adjusting for factors that could influence the relationship such as age, sex, education, smoking, and physical activity. Nut intake was inversely associated with the other outcomes but lost significance after adjustment.

ESC guidelines list 30 grams of unsalted nuts per day as one of the characteristics of a healthy diet, while noting that the energy density of nuts is high.(1)

“Raw fresh nuts are the healthiest,” added Dr Mohammadifard. “Nuts should be fresh because unsaturated fats can become oxidised in stale nuts, making them harmful. You can tell if nuts are rancid by their paint-like smell and bitter or sour taste.”

References and notes

(1)Piepoli MF, Hoes AW, Agewall S, et al. 2016 European Guidelines on cardiovascular disease prevention in clinical practice. Eur Heart J. 2016;37:2315-2381.

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Cardiovascular disease (CVD) is responsible for more than four million deaths in Europe each year. Clogged arteries, known as atherosclerotic CVD, are the main type of disease. The guidelines provide recommendations on how to modify plasma lipid levels through lifestyle and medication to reduce the risk of atherosclerotic CVD.

“There is now overwhelming evidence from experimental, epidemiological, genetic studies, and randomised clinical trials, that higher LDL cholesterol is a potent cause of heart attack and stroke,” said Professor Colin Baigent, Chairperson of the guidelines Task Force and director of the MRC Population Health Research Unit, University of Oxford, UK. “Lowering LDL cholesterol reduces risk irrespective of the baseline concentration. It means that in people at very high risk of heart attack or stroke, reducing LDL cholesterol is effective even if they have below average starting levels.”

There is no lower limit of LDL cholesterol that is known to be unsafe. The guidelines aim to ensure that the available drugs (statins, ezetimibe, PCSK9 inhibitors) are used as effectively as possible to lower levels in those most at risk. It is recommended that such patients should achieve both a target LDL cholesterol level and a minimum 50% relative reduction.

“This is to ensure that high- or very high-risk patients receive intensive LDL cholesterol lowering therapy irrespective of their baseline level,” said Professor Alberico L. Catapano, Chairperson of the guidelines Task Force and professor of pharmacology at the Department of Pharmacological and Biomolecular Sciences, University of Milan, Italy. “Patients who are already close to their target on current treatment will be offered additional treatment that provides a further minimum 50% reduction.”

“Statins are very well tolerated, and true ‘statin intolerance’ is uncommon. Most patients can take a statin regimen,” noted Professor François Mach, Chairperson of the guidelines Task Force and head of the Cardiology Department, Geneva University Hospital, Switzerland. “Statins have very few side-effects. These include an increased risk of developing diabetes, and they may rarely cause myopathy. But the benefits of statins greatly outweigh their hazards, even among those at low risk of atherosclerotic CVD.”

However, statins are not recommended in pre-menopausal women considering pregnancy or not using adequate contraception. “Although these drugs have not been shown to cause fetal malformations when unintentionally used in the first trimester of pregnancy, women needing a statin should avoid them during any period when they might conceive, as no formal study to address this question has been performed,” said Prof Catapano.

The evidence for statin therapy is more limited in patients over 75, though is still consistent with a benefit. The guidelines advise taking level of risk, baseline LDL cholesterol, health status, and the risk of drug interactions into account when deciding whether statins are appropriate in those aged 75 or over.

Revisions have been made to the risk stratification categories so that patients with atherosclerotic CVD, diabetes with target organ damage, familial hypercholesterolaemia, and severe chronic kidney disease are all categorised as very high-risk (and so will be offered intensive LDL-lowering therapy). Treatment goals for a particular risk category apply regardless of whether or not patients have had a heart attack or stroke.

Evidence since the 2016 guidelines suggests that raised Lp(a) is a cause of atherosclerotic CVD, and patients with genetically elevated Lp(a) can have similar lifetime risk of heart attack or stroke as those with familial hypercholesterolaemia. Since Lp(a) is largely genetically determined, the guidelines recommend measuring it at least once in adulthood. “Assessment should be around 40 years of age to identify people before they have a heart attack or stroke,” said Prof Baigent.

Fish oil supplements (particularly icosapent ethyl) are recommended, in combination with a statin, for patients with hypertriglyceridaemia despite statin treatment. In these patients, supplements reduce the risk of atherosclerotic CVD events, including heart attack and stroke, by about one quarter.

The guidelines advocate a lifetime approach to cardiovascular risk. This means that people of all ages and risk levels should be encouraged to adopt and sustain a healthy lifestyle. “The main requirements are healthy diet, avoidance of cigarette smoking, and regular exercise,” said Prof Mach. “There is no evidence that fish oil supplements prevent first heart attacks and strokes, so we did not recommend them for healthy people.”