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24th February 2023
Women who experience pregnancy hypertensive disorders such as preeclampsia have a higher risk of developing cardiovascular disorders in the future according to the findings of a Mendelian randomisation analysis by UK and Dutch researchers.
Hypertensive disorders during pregnancy affect 8% to 10% of all pregnant women and can lead to serious complications including mortality. In fact, one systematic analysis revealed how 14% of maternal deaths were due to hypertensive disorders. Moreover, observational evidence suggests that having a pregnancy-related hypertensive disorder increases the risk of cardiovascular events in later life. Nevertheless, observational data cannot be used to determine a causal relationship due to potential confounding. However, a better study design that can determine whether such a relationship is causal is the use of Mendelian randomisation (MR). This approach uses the genetic risk of disease as a proxy for the disease itself and can be used to mitigate the effect of confounding, as the MR estimate can be used to interpret the effect of the exposure, in this case pregnancy-related hypertensive diseases, on the outcome of interest (cardiovascular disease).
In the current study, researchers used estimates of genetic association obtained from genome-wide association data, to examine the association between gestational hypertension and preeclampsia and the risk of subsequently developing coronary artery disease, ischaemic stroke, heart failure and atrial fibrillation. The team also employed mediation analysis based on multivariable MR, to consider the impact of potential mediators e.g., body mass index, systolic blood pressure etc, on any identified associations.
Pregnancy hypertensive disorders and future cardiovascular risk
For any genetically predicted hypertensive disorder, there was an elevated risk of developing coronary artery disease (Odds ratio, OR = 1.24, 95% CI 1.08 – 1.43, p = 0.02). The risk was also elevated when considering gestational hypertension (OR = 1.08, p = 0.04), preeclampsia or eclampsia (OR = 1.06, p = 0.03) and ischaemic stroke (OR = 1.27, P < 0.001). However, the risks were non-significant for both gestational hypertension and preeclampsia and there were also non-significant for both heart failure and atrial fibrillation.
In the mediation analysis, there was a partial attenuation of the overall risk for CAD after adjusting for systolic blood pressure (adjusted OR = 1.10 vs 1.24) and the presence of type 2 diabetes (adjusted OR = 1.16 vs 1.24).
The authors concluded that given their findings, the presence of pregnancy-related hypertensive disorders should be considered as risk factors for cardiovascular disease.
Citation
Rayes B et al. Association of Hypertensive Disorders of Pregnancy With Future Cardiovascular Disease. JAMA Netw Open. 2023
3rd February 2023
Depression and poor mental health among young adults is more likely to lead to premature cardiovascular disease (CVD) and suboptimal cardiovascular health according to the findings of a large study of US adults by US and UK researchers.
A worrying trend over the past 20 years is the observed increase in the prevalence of recognised cardiovascular disease risk factors e.g., obesity, physical inactivity and a poor diet, among younger individuals in developed countries. Moreover, though not considered as a traditional CVD risk factor, the American Heart Association accepts that depression should be considered as a risk factor for adverse outcomes in patients with acute coronary syndrome. But to what extent does the presence of depression or even poor mental health, affect the risk of CVD among younger adults was the subject of the current study.
Researchers used data from the behavioural risk factor surveillance system which includes a nationally representative sample of non-institutionalised adults. The system assesses health-related risk behaviours and chronic health conditions, based on an annual telephone survey. The research team collected data on self-reported depression and poor mental health days (PMHDs), as well as CVD and suboptimal cardiovascular (CV) health, based on recognised risk factors, e.g., smoking, physical inactivity. In addition, self-reported PMHDs were categorised as 0, 1 – 13 or 14 to 30.
Depression and risk of premature cardiovascular disease
In total, data were collected from 593,616 with a mean age of 34.7 years (50.3% male).
The prevalence of depression was 19.6% and 2.5% for CVD. The researchers calculated that those with depression had a much higher odds of CVD compared to those without the condition (odds ratio, OR = 2.32, 95% CI 2.13 – 2.51). There was also a graded increased risk of CVD, depending on the number of reported PMHDs rising from an odds ratio of 1.48 (1 to 13 days) to 2.29 (14 to 30 days). These estimates were unaffected by gender or individual’s status (rural or urban). Suboptimal cardiovascular health was also higher among those with depression (OR = 1.79) and a similar graded relationship observed based on the number of PMHDs.
The authors concluded that based on their findings, prioritising mental health might help to reduce CVD risk and improve cardiovascular health in young adults.
Citation
Kwapong YA et al. Association of Depression and Poor Mental Health With Cardiovascular Disease and Suboptimal Cardiovascular Health Among Young Adults in the United States. J Am Heart Assoc 2023
17th November 2022
The small interfering RNA olpasiran has been found to virtually eliminate lipoprotein A in patients with atherosclerotic cardiovascular disease according to the findings of a randomised, placebo-controlled trial by US researchers.
Lipoprotein A (LPA) is a large glycoprotein attached to a low-density lipoprotein-like particle, that is associated with a risk of coronary heart disease and stroke. Lipoprotein A is produced by the apo(a) gene and levels are genetically determined with higher levels increasing the risk of atherosclerotic disease via mechanisms associated with increased atherogenesis, inflammation, and thrombosis. Despite this known link and therefore risk of cardiovascular disease, there are currently no pharmacological therapies available to reduce its levels. Olpasiran is a small interfering molecule that interrupts the expression of the LPA gene by degrading the messenger RNA that encodes the apo(a) protein. In a preclinical study with mice, olpasiran reduced LPA concentrations by 80% from baseline for 5 – 8 weeks after administration of a single dose. Based on these findings, the US researchers undertook the Olpasiran Trials of Cardiovascular Events and Lipoprotein[a] Reduction–Dose Finding Study to assess the efficacy and safety of repeated administration of the product.
Individuals aged 18 to 80 with serum LPA levels higher than 150nmol/L and a history of atherosclerotic cardiovascular disease were included. These participants were randomised 1:1:1: 1:1 to receive four doses of olpasiran administered subcutaneously (10 mg, 75 mg, 225 mg every 12 weeks) and 225 mg every 24 weeks or matching placebo, for a period of 48 weeks. The primary endpoint was the percentage change in the LPA concentration from baseline to week 36 whereas the secondary outcome was the change at the end of the trial.
Olpasiran and Lipoprotein A levels
A total of 281 participants with a mean age of 61.9 years (32% female) were enrolled and randomised to one of the five arms (between 54 and 58 per arm). The overall median baseline LPA level was 260.3 nmol/L and 88% of participants were taking a statin and 23% a proprotein convertase subtilisinkexin type 9 (PCSK9) inhibitor.
At week 36, the LPA level increased by 3.6% in the placebo group but was significantly reduced in each of the active treatment arms. For example, the placebo-adjusted change in the 10 mg group was -70.5%, -97.4% in the 75 mg group and -101.1% in the 225 mg group and -100.5% in the 225 mg arm when administered every 24 weeks (p < 0.001 for all comparisons with the baseline value).
In addition, LDL cholesterol levels were also reduced with placebo-adjusted reductions ranging from -22.6% to -24.8%.
Adverse effects were generally similar across the groups.
The authors concluded that olpasiran significantly reduced lipoprotein(a) concentrations in patients with established atherosclerotic cardiovascular disease and called for future trials to assess the impact of treatment on cardiovascular disease.
Citation
O’Donoghue ML et al. Small Interfering RNA to Reduce Lipoprotein(a) in Cardiovascular Disease. N Eng J Med 2022
10th November 2022
Patients with thyroid cancer (TC) have a greater risk of developing coronary heart disease and in those under 65 years of age, this elevated risk persists for at least five years after their cancer diagnosis according to an observational study by Taiwanese researchers.
In 2020, the global estimated rate of thyroid cancer was 10·1 per 100 000 women and 3·1 per 100 000 men, although mortality rates were lower at 0·5 per 100 000 and 0·3 per 100 000 for women and men respectively. Surgery is the mainstay of treatment in nearly every case of thyroid cancer although radiotherapy can also be used. If the thyroid is removed, then patients will require life-long therapy with levothyroxine both to replace the hormone and lower the risk of cancer recurrence. However, long-term use of levothyroxine may cause marked impairment of cardiac functional reserve and physical exercise capacity. Whether these changes increase the subsequent risk of cardiovascular disease remains uncertain with some evidence that such patients have a higher incidence of cardiovascular disease morbidity. In contrast however, other work has shown that the incidence of cerebrovascular disease, cerebral infarction, ischaemic heart disease, ischaemic heart attack and heart failure are no different between those with TC and the general population.
With some uncertainty over the relationship between TC and the risk of cardiovascular diseases, in the current study, the Taiwanese researchers turned to data contained within a nationwide population-based cohort to retrospectively examine this relationship. They chose a baseline date for their analysis as the time when TC patients underwent a thyroidectomy but excluded those aged < 20 and > 85 years and anyone with a history of coronary heart disease (CHD) or atrial fibrillation. They set the primary endpoint of interest as hospitalisation for CHD defined in terms of fatal and non-fatal CHD. Secondary outcomes included ischaemic stroke (IS) that required hospitalisation and atrial fibrillation, which again required hospitalisation. The researchers calculated a standardised incidence ratio (SIR) as the ratio of observed to expected CHD cases, stratified by age and gender within the general population.
Thyroid cancer and risk of coronary heart disease
A total of 4,274 individuals who had thyroid cancer without CHD and a mean age of 49 years (24.4% male) were included in the analysis and followed-up for a mean of 3.5 years.
During follow-up, there were 69 CHD events in those with TC and the SIR was significantly higher than expected in the age-standardised population (SIR = 1.57, 95% CI 1.2 – 1.93). However, the rate of IS was not significantly different (SIR = 0.74, 95% CI 0.47 – 1), neither was the incidence of cardiovascular disease (SIR = 0.88, 95% CI 0.70 – 1.05) or atrial fibrillation (SIR = 0.74, 95% CI 0.42 – 1.06).
When researchers considered the SIR over time, particularly among those under 65 years of age, the elevated risk remained significant, 5 years after the date of their TC diagnosis (SIR = 2.08, 95% CI 1.5 – 2.66) although it was non-significant among those over 65 years of age (SIR = 1.0, 95% CI 0.57 – 1.42).
The authors concluded that thyroid cancer patients had a greater risk of CHD than the general population without the cancer and that this risk persisted for at least 5 years. They called for future research to further investigate this observed association.
Citation
Tsai MC et al. Association between thyroid cancer and cardiovascular disease risk: a nationwide observation study. Sci Rep 2022
7th October 2022
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
6th October 2022
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
16th September 2022
The benefits of statin therapy against cardiovascular disease are life-long because a large share of the benefit occurs later in life according to the results of a modelling study by researchers from Queen Mary University of London, UK and presented at European Society of Cardiology congress in Barcelona, Spain.
According to the 2021 ESC Guidelines on cardiovascular disease prevention in clinical practice, the causal role of LDL-C, and other apo-B containing lipoproteins, in the development of atherosclerotic cardiovascular disease, is demonstrated beyond any doubt by genetic, observational, and interventional studies. Statin therapy is designed to lower LDL-C cholesterol and a 2016 meta-analysis of 26 randomised controlled trials with over 170,000 patients, found that all-cause mortality was reduced by 10% per 1·0 mmol/L LDL reduction, largely reflecting significant reductions in deaths due to coronary heart disease and other cardiac causes. Despite these clear benefits, there is some uncertainty about when to start and how long to persist, with statin therapy, to optimise the effects. In the present study, the UK researchers estimated the accumulation of benefit from statin therapy, according to age of initiation, using a microsimulation model that was developed using data on 118,000 participants of large international statin trials from the Cholesterol Treatment Trialists’ Collaboration and 500,000 individuals in the UK Biobank population cohort. The model used individual characteristics (e.g. age, sex) and disease histories to simulate the annual risk of heart attack, stroke, coronary revascularisation, diabetes, cancer, vascular death and nonvascular death for each participant. Treatment with a standard dose of statin (40 mg daily) was used to estimate the effect of therapy versus no therapy in these scenarios: (1) lifelong therapy (used until death or 110 years of age if earlier), (2) therapy stopped at 80 years of age, and (3) delayed initiation of therapy by five years in participants under 45 years of age. The benefit of statin therapy was measured in quality-adjusted life years (QALYs), which represents the length of life adjusted by health to reflect quality of life. For example, one QALY is equal to one year of life in perfect health. Benefits were also reported separately according to baseline cardiovascular risk, which refers to the likelihood of having a heart attack or stroke in the next 10 years, and is based on age, blood pressure, cholesterol levels, smoking status, and medical conditions
Statin therapy benefits
The researchers found that a large part of QALYs gained with statin therapy accrued later in life. The higher the participants’ 10-year cardiovascular risk, the larger and earlier the statin benefit accrued. Compared with lifelong statins, stopping therapy at 80 years of age, would erase a large share of the potential benefit, especially for people with relatively low cardiovascular risk.
According to lead author of the study Dr Runguo Wu ‘the study indicates that people in their 40s with a high likelihood of developing cardiovascular disease, and people of all ages with existing heart disease, should be considered for immediate initiation of cholesterol lowering treatment. Stopping treatment, unless advised by a doctor, does not appear to be a wise choice.’
They added that ‘our study suggests that people who start taking statins in their 50s but stop at 80 years of age instead of continuing lifelong, will lose 73% of the QALY benefit if they are at relatively low cardiovascular risk and 36% if they are at high cardiovascular risk – since those at elevated risk start to benefit earlier. Women’s cardiovascular risk is generally lower than men’s. This means that for women, most of the lifelong benefit from statins occurs later in life and stopping therapy prematurely is likely more detrimental than for men.’
It was also important to understand that the benefits of statin therapy was dependent upon an individual’s baseline risk. For example, for some one under 45 years of age at low cardiovascular risk, (i.e., less than 5% likelihood of heart attack or stroke in the next 10 years) a five-year delay in taking statins had little impact – they lost just 2% of the potential QALY benefit from lifelong therapy. However, the impact was larger in people under 45 years of age at high cardiovascular risk, meaning a more than 20% likelihood of heart attack or stroke in the next 10 years – they lost 7% of the potential QALY benefit from lifelong therapy. Dr. Wu said: “Again, this is because people at higher cardiovascular risk start to accrue benefit early on and have more to lose by delaying statin therapy than those at low risk.’
27th April 2022
A higher avocado intake reduces the risk of cardiovascular disease according to the findings from two large prospective studies reported by researchers from Harvard T.H. Chan School of Public Health, Boston, USA.
Cardiovascular disease (and which also includes coronary heart disease) represents the leading cause of death globally. Interestingly, studies suggest that there is a valid association between several dietary factors and patterns with coronary heart disease. One healthy food is avocado, which contains a large amount (71%) of monounsaturated fatty acids and helps to promote healthy blood lipid profiles, enhancing the bioavailability of fat soluble vitamins and phyto-chemicals from the avocado or other fruits and vegetables. In fact, there are data showing how avocado consumption is associated with a reduced risk of metabolic syndrome and other work has indicated that eating at least one avocado each day provides a beneficial effect on cardio-metabolic risk factors that extended beyond their heart-healthy fatty acid profile. Furthermore, a recent systematic review found that avocado intake increased serum HDL-cholesterol concentrations, prompting the authors to suggest that the association between avocado intake and cardiovascular risk should be confirmed by well-conducted prospective observational studies or long-term trials.
For the present study, the US team examined the association between a higher avocado intake and cardiovascular outcomes. They turned to data held in both the Nurse’s Health Study (NHS) and the Health Professionals Follow-up Study (HPFS), which are two prospective cohort studies which were initiated in the 1970’s and 1980’s respectively. In both of these cohort studies, participants were asked to complete validated questionnaires asking about lifestyle and diet every 2 years and from this information, the researchers were able to determine how much avocado was consumed. This was then categorised as never or less than once a month, 1 – 3 times per month, weekly and > twice a week. The primary outcome of interest was incident cases of total cardiovascular disease, which was a composite of several adverse cardiovascular outcomes e.g., fatal coronary heart disease. The main secondary outcome related to strokes.
Higher avocado intake and adverse cardiovascular outcomes
A total of 68,786 women from the NHS and 41,701 men from the HPFS who were free of cardiovascular disease and stroke at baseline were included and followed for 30 years (median for men was 13.3 years and 14.2 for women). During follow-up there were a total of 14,274 cases of cardiovascular disease (CVD) in both NHS and HPFS.
After adjustments were made for dietary and lifestyle factors, compared to those who did not eat avocados, individuals with a higher avocado intake (> twice/week) week had a 16% lower risk of CVD (hazard ratio, HR = 0.84, 95% CI 0.75 – 0.95) and a 21% lower risk of coronary heart disease (HR = 0.79, 95% CI 0.68 – 0.91). However, there was no significant reduction for stroke.
The authors calculated that for each half serving/day increase in avocado intake, the pooled hazard ratio for CVD was 0.80. In fact, the authors added that by replacing half a serving/day of margarine, butter, egg, yoghurt, cheese or processed meats with the equivalent amount of avocado would be associated with a 16 to 22% lower risk of CVD.
Citation
Pacheco LS et al. Avocado Consumption and Risk of Cardiovascular Disease in US Adults J Am Heart Assoc 2022
11th April 2022
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.
24th March 2022
The use of a cocoa extract containing flavanols did not reduce the overall incidence of cardiovascular events but did lower the incidence of cardiovascular deaths. This was the main finding of a randomised trial by researchers from the Division of Preventive Medicine, Brigham and Women’s Hospital, Boston, US.
Flavan-3-ols, which are a subclass of flavonoids, represent a type of poly-phenolic substances which are present in a range of plants such as cocoa and cocoa containing foods such as chocolate. Furthermore, research demonstrates a beneficial effect of cocoa on blood pressure, insulin resistance, and vascular and platelet function. As well as flavonoids, a cocoa extract typically contains other ingredients such as epicatechin and the methylxanthines, theobromine and caffeine. In fact, studies suggest how the presence of these latter components mediate an increased plasma concentration of epicatechin metabolites that coincides with enhanced vascular effects. To date, much research which has focused on the cardiovascular effect of cocoa containing products such as chocolate, and suggests a small inverse association between consumption and both coronary heart disease and stroke. However, there is a lack of data from large-scale trials, on the cardiovascular benefits of a flavanol-rich cocoa extract which contains all the bioactive compounds present in the cocoa bean.
As a result, the US team undertook the Cocoa Supplement and Multivitamin Outcome Study (COSMOS), a pragmatic, randomised trial which sought to examine the effect of a cocoa extract on cardiovascular disease and cancer in older adults. For the present study, the authors have only reported on the cardiovascular outcomes.
The team recruited adults over 65 years of age, who were initially free of major cardiovascular disease and given either a cocoa extract containing 500 mg/day of cocoa flavanols and a multivitamin supplement or matching placebo. All participants were required to stop taking cocoa supplements (although chocolate could still be eaten) and a blood biomarker of flavanol intake were initially measured and repeated after years 1, 2 and 3. The primary outcome was a composite of total cardiovascular disease (CVD) outcomes including myocardial infarction (MI), stroke, cardiovascular mortality and coronary revascularisation. The authors then set the secondary outcomes as the individual components of the primary outcome, i.e., cardiovascular death, stroke etc.
Cocoa extract and cardiovascular outcomes
A total of 21,442 individuals with a mean age of 72.1 years (59.1% female) were randomised to cocoa (10,719) or placebo and followed for a median of 3.6 years. Based on an analysis of plasma samples, there was a three-fold higher increase compared to placebo, in the levels of flavanol biomarker and this did not differ between follow-up assessment.
During the follow-up period there were 866 confirmed cardiovascular events, 410 in those taking the cocoa extract and 456 in the placebo group, giving a hazard ratio, HR of 0.90 (95% CI 0.78 – 1.02, p = 0.11).
For the secondary outcomes, only cardiovascular death was significantly different (HR = 0.73, 95% CI 0.54 – 0.98).
The authors concluded that while the cocoa extract did not reduce the primary outcome, longer follow-up of trial participants may further elucidate the relationship between consumption of the extract and cardiovascular events.
Citation
Sesso HD et al. Effect of Cocoa Flavanol Supplementation for Prevention of Cardiovascular Disease Events: The COSMOS Randomized Clinical Trial Am J Clin Nutr 2022
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