Ultrasound breakthrough can pinpoint cancer with precision

Heriot Watt University | September 2019 | Ultrasound breakthrough can pinpoint cancer with precision

Experts at Heriot Watt University have found a new technique which uses super-resolution ultrasound methods that improves resolution of ultrasound images by 5-10 times compared to standard current ultrasound images.

Their innovation allows whole organs to be scanned in super-resolution for the first time which, it is anticipated, will lead to earlier cancer diagnoses and allow medical staff to more effectively target treatments to any malignant tissue. Potentially, it could eventually replace the need for biopsy altogether.

The team behind this innovation  the aim is to start human trials using the new technique in three months’ time at the Western General Hospital in Edinburgh. Patients with prostate issues will be the first to benefit from the enhanced imaging.

Professor Alan McNeill, Consultant Urological Surgeon at the Western General Hospital in Edinburgh said: “Prostate cancer is an increasing problem for our society. Whilst we have a number of methods for detecting it, these don’t always provide us with the important information that we need regarding who has cancer that needs to be treated and who doesn’t.

“A method that maps the blood flow of the tumour accurately could well provide new information about the disease state that allows us to better identify those men who need urgent treatment and those who don’t. It is exciting that we will be the first hospital in the world that will assess this method with patients.” (Source: Heriot Watt University)

Read the full, unabridged press release from Heriot Watt University

Abstract

Objectives The aim of this study was to provide an ultrasound-based super-resolution methodology that can be implemented using clinical 2-dimensional ultrasound equipment and standard contrast-enhanced ultrasound modes. In addition, the aim is to achieve this for true-to-life patient imaging conditions, including realistic examination times of a few minutes and adequate image penetration depths that can be used to scan entire organs without sacrificing current super-resolution ultrasound imaging performance.

Methods Standard contrast-enhanced ultrasound was used along with bolus or infusion injections of SonoVue (Bracco, Geneva, Switzerland) microbubble (MB) suspensions. An image analysis methodology, translated from light microscopy algorithms, was developed for use with ultrasound contrast imaging video data. New features that are tailored for ultrasound contrast image data were developed for MB detection and segmentation, so that the algorithm can deal with single and overlapping MBs. The method was tested initially on synthetic data, then with a simple microvessel phantom, and then with in vivo ultrasound contrast video loops from sheep ovaries. Tracks detailing the vascular structure and corresponding velocity map of the sheep ovary were reconstructed. Images acquired from light microscopy, optical projection tomography, and optical coherence tomography were compared with the vasculature network that was revealed in the ultrasound contrast data. The final method was applied to clinical prostate data as a proof of principle.

Results Features of the ovary identified in optical modalities mentioned previously were also identified in the ultrasound super-resolution density maps. Follicular areas, follicle wall, vessel diameter, and tissue dimensions were very similar. An approximately 8.5-fold resolution gain was demonstrated in vessel width, as vessels of width down to 60 μm were detected and verified (λ = 514 μm). Best agreement was found between ultrasound measurements and optical coherence tomography with 10% difference in the measured vessel widths, whereas ex vivo microscopy measurements were significantly lower by 43% on average. The results were mostly achieved using video loops of under 2-minute duration that included respiratory motion. A feasibility study on a human prostate showed good agreement between density and velocity ultrasound maps with the histological evaluation of the location of a tumor.

Conclusions The feasibility of a 2-dimensional contrast-enhanced ultrasound-based super-resolution method was demonstrated using in vitro, synthetic and in vivo animal data. The method reduces the examination times to a few minutes using state-of-the-art ultrasound equipment and can provide super-resolution maps for an entire prostate with similar resolution to that achieved in other studies.

The original research is available in full from Investigative Radiology

In the news:

BBC News Ultrasound breakthrough ‘can spot cancer earlier’

Scientists discover new breakthrough in cancer hair loss treatment

University of Manchester| September 2019 |Scientists discover new breakthrough in cancer hair loss treatment

Scientists at the University of Manchester have discovered that damage in the hair follicle causing by taxanes cancer drugs which can cause permanent hair loss, can be prevented. Taxanes are very important anti-cancer drugs commonly used to treat, for example, patients with breast or lung carcinoma and particularly cause anxieties among breast cancer patients for the very distressing and sometimes long-lasting hair loss taxanes can induce. 

Image source: Purba et al 2019

Lead author of the study Dr Talveen Purba explains:

Dr Purba emphasises: “A pivotal part of our study was to first get to grips with how exactly hair follicles responded to taxane chemotherapy, and we found that the specialised dividing cells at the base of the hair follicle that are critical for producing hair itself, and the stem cells from which they arise, are most vulnerable to taxanes. Therefore, we must protect these cells most from undesired chemotherapy effects – but so that the cancer does not profit from it.”

The team hope that their work will support the development of externally applicable medicines that will slow or briefly suspend cell division in the scalp hair follicles of patients undergoing chemotherapy to mitigate against chemotherapy-induced hair damage. This could complement and enhance the efficacy of existing preventive approaches i.e. scalp cooling devices (Source: University of Manchester)

The full new story is available from the University of Manchester

Full reference: Purba, T. S. et al 2019| CDK4/6 inhibition mitigates stem cell damage in a novel model for taxane‐induced alopecia| EMBO molecular medicine| https://doi.org/10.15252/emmm.201911031

Abstract

Taxanes are a leading cause of severe and often permanent chemotherapy‐induced alopecia. As the underlying pathobiology of taxane chemotherapy‐induced alopecia remains poorly understood, we investigated how paclitaxel and docetaxel damage human scalp hair follicles in a clinically relevant ex vivo organ culture model. Paclitaxel and docetaxel induced massive mitotic defects and apoptosis in transit amplifying hair matrix keratinocytes and within epithelial stem/progenitor cell‐rich outer root sheath compartments, including within Keratin 15+ cell populations, thus implicating direct damage to stem/progenitor cells as an explanation for the severity and permanence of taxane chemotherapy‐induced alopecia. Moreover, by administering the CDK4/6 inhibitor palbociclib, we show that transit amplifying and stem/progenitor cells can be protected from paclitaxel cytotoxicity through G1 arrest, without premature catagen induction and additional hair follicle damage. Thus, the current study elucidates the pathobiology of taxane chemotherapy‐induced alopecia, highlights the paramount importance of epithelial stem/progenitor cell‐protective therapy in taxane‐based oncotherapy, and provides preclinical proof‐of‐principle in a healthy human (mini‐) organ that G1 arrest therapy can limit taxane‐induced tissue damage.

 

The article can be read online or downloaded

 

 

 

 

Case study: ADENOMA – impact case study

NIHR | September 2019 | Case study: ADENOMA – impact case study

NIHR has produced an impact case study on adenoma, a polyp that grows in the bowel that has become cancerous.  Currently, a colonoscopy is regarded as the ‘gold standard’ treatment for adenoma.

Although experienced endoscopists perform the colonoscopies, polyps can get missed for various reasons including the size, shape and location of the lesions, and many colorectal cancer screening programmes have been proposed to improve adenoma detection rate (ADR). Improving the ADR and cancer detection through increased colonoscopy performance brings patient benefits, and earlier diagnosis of cancer is also associated with lower healthcare costs (Cancer Research UK 2014).

The study recruited 1800 participants from across seven sites, with patients being referred to the trial because of symptoms, surveillance or following a positive faecal occult blood test as part of the Bowel Cancer Screening Programme.

These patients were randomized across two arms of the trial: with one group having treatment as usual (the colonoscopy) and the other having the Endocuff Vision arm

The researchers report that the participants in the Endocuff Vision arm of the trial, had a higher Adenoma Detection Rate, increased globally from 36.2 per cent to 40.9 per cent (P=0.02). the increase was driven by a 10.8 per cent increase in FOBt-positive screening patients (50.9 per cent vs 61.7 per cent, P less than 0.001).

The research team conclude that the ADENOMA trial showed that Endocuff Vision significantly improved ADR in bowel cancer screening patients and should be used to improve colonoscopic detection.

The success of the trial led to NHS England announcing Endocuff Vision as one of only four technologies to be fast-tracked into use through NHS England’s Innovation and Technology Payment programme in April 2018.

NICE updated its guidelines for use in June 2019 and NHS trusts across England have significantly increased use of the product.
The Endocuff Vision device has also been adopted internationally and there has been a large rise in the use of the device over the last four years (Source: NIHR).

Read the full story from NIHR

 

BMJ: Cancer screening uptake- only a third of women take up offers

Torjesen, I. | 2019| Cancer screening: only a third of women in England take up all offers | BMJ| 366 | l5588 | doi: https://doi.org/10.1136/bmj.l5588

A new study published in the BMJ indicates that of the screening services offered to women in their 60s, which include cervical, breast and bowel screening only a third attend these screening sessions.  

The study included over 3000 women aged between 60-65 who had responded to their last invitations from each of these three screening programmes.

Results showed that:

• 35% took part in all three screening programmes;
• 37% participated in two programmes;
• 17% accessed one type of screening; and
• 10% were not screened at all.

They found that in the last screening round, 2525 (83%) had taken up mammography, 1908 (62%) cervical screening, and 1635 (53%) bowel cancer screening, which is consistent with the proportions reported in the official statistics for England (78%, 58-59%, and 57-59%, respectively).

The researchers also explored area level correlations between participation in the three screening programmes and various population characteristics for all English general practices with complete data in the Fingertips database curated by Public Health England. This database reports health related data for England aggregated by administrative area.

General practices with higher proportions of unemployed patients and smokers had a lower rate of take-up of all three screening programmes. Conversely, general practices from areas with less deprivation, with more patients who are carers or have chronic illnesses themselves, and with more patients satisfied with the provided service were significantly more likely to attain high coverage rates in all programmes (Source:  Torjesen, 2019).

Abstract

Objectives

To determine how many women participate in all three recommended cancer screening programmes (breast, cervical, and bowel). During their early 60s, English women receive an invitation from all the three programmes.

Methods

For 3060 women aged 60–65 included in an England-wide breast screening case–control study, we investigated the number of screening programmes they participated in during the last invitation round. Additionally, using the Fingertips database curated by Public Health England, we explored area-level correlations between participation in the three cancer screening programmes and various population characteristics for all 7014 English general practices with complete data.
Results

Of the 3060 women, 1086 (35%) participated in all three programmes, 1142 (37%) in two, 526 (17%) in one, and 306 (10%) in none. Participation in all three did not appear to be a random event (p  less than 0.001). General practices from areas with less deprivation, with more patients who are carers or have chronic illnesses themselves, and with more patients satisfied with the provided service were significantly more likely to attain high coverage rates in all programmes.

Conclusions

Only a minority of English women is concurrently protected through all recommended cancer screening programmes. Future studies should consider why most women participate in some but not all recommended screening.

 

See also: King’s College London Only a third of women take up all offered cancer screenings, new research finds

BMJ Cancer screening: only a third of women in England take up all offers

Increasing incidence of colorectal cancer in young adults in Europe over the last 25 years

Vuik, F.E., et al | 2019| Increasing incidence of colorectal cancer in young adults in Europe over the last 25 years| Gut|68| P.1820-1826|

Research published in the journal Gut analyses trends in the incidence of colorectal cancer (CRC) and mortality in subjects under the age of 50. The experts used data on over 143 million people across European countries to explore . While the researchers observed that CRC incidence continues to rise among young adults in Europe; they indicate further research is necessary to find out the reasons for this trend need to be discovered and if the trend continues, screening guidelines may need to be reconsidered.

The full article is available from the journal Gut

Abstract

Objective The incidence of colorectal cancer (CRC) declines among subjects aged 50 years and above. An opposite trend appears among younger adults. In Europe, data on CRC incidence among younger adults are lacking. We therefore aimed to analyse European trends in CRC incidence and mortality in subjects younger than 50 years.

 

Design Data on age-related CRC incidence and mortality between 1990 and 2016 were retrieved from national and regional cancer registries. Trends were analysed by Joinpoint regression and expressed as annual percent change.

 

Results We retrieved data on 143.7 million people aged 20–49 years from 20 European countries. Of them, 187 918 (0.13%) were diagnosed with CRC. On average, CRC incidence increased with 7.9% per year among subjects aged 20–29 years from 2004 to 2016. The increase in the age group of 30–39 years was 4.9% per year from 2005 to 2016, the increase in the age group of 40–49 years was 1.6% per year from 2004 to 2016. This increase started earliest in subjects aged 20–29 years, and 10–20 years later in those aged 30–39 and 40–49 years. This is consistent with an age-cohort phenomenon. Although in most European countries the CRC incidence had risen, some heterogeneity was found between countries. CRC mortality did not significantly change among the youngest adults, but decreased with 1.1%per year between 1990 and 2016 and 2.4% per year between 1990 and 2009 among those aged 30–39 years and 40–49 years, respectively.

 

Conclusion CRC incidence rises among young adults in Europe. The cause for this trend needs to be elucidated. Clinicians should be aware of this trend. If the trend continues, screening guidelines may need to be reconsidered.

Full article available from the BMJ

 

See also:

Reuters Colorectal cancer becoming more common at younger ages

Cancer Research UK Bowel cancer rates are rising in young adults, but do we know what’s behind the increase?

UK cancer survival rates lag behind similar countries

Arnold, M. et al |2019| Progress in cancer control: survival, mortality and incidence in seven high-income countries 1995-2014 (the ICBP SURVMARK-2 project)| The Lancet | Doi:https://doi.org/10.1016/S1470-2045(19)30456-5

The Cancer Survival in High-Income Countries (SURVMARK-2), is a longitudinal, population-based study which aims to provide a comprehensive overview of cancer survival across seven high-income countries and a comparative assessment of corresponding incidence and mortality trends.

Image source: scienceblog.cancerresearchuk.org

While the study’s evaluation indicated progress in four of the seven studied cancers. Cancer survival continues to increase across high-income countries; however, international disparities persist. The UK was behind Australia, New Zealand, Noway, Canada, Denmark and Norway. Some of the lowest rates of 1-year survival was observed for stomach, colon, rectal, and lung cancer in the UK (Source: Arnold, et al, 2019).

Summary

Background

Population-based cancer survival estimates provide valuable insights into the effectiveness of cancer services and can reflect the prospects of cure. As part of the second phase of the International Cancer Benchmarking Partnership (ICBP), the Cancer Survival in High-Income Countries (SURVMARK-2) project aims to provide a comprehensive overview of cancer survival across seven high-income countries and a comparative assessment of corresponding incidence and mortality trends.

 

Methods

In this longitudinal, population-based study, we collected patient-level data on 3·9 million patients with cancer from population-based cancer registries in 21 jurisdictions in seven countries (Australia, Canada, Denmark, Ireland, New Zealand, Norway, and the UK) for seven sites of cancer (oesophagus, stomach, colon, rectum, pancreas, lung, and ovary) diagnosed between 1995 and 2014, and followed up until Dec 31, 2015. We calculated age-standardised net survival at 1 year and 5 years after diagnosis by site, age group, and period of diagnosis. We mapped changes in incidence and mortality to changes in survival to assess progress in cancer control.

 

Findings

In 19 eligible jurisdictions, 3 764 543 cases of cancer were eligible for inclusion in the study. In the 19 included jurisdictions, over 1995–2014, 1-year and 5-year net survival increased in each country across almost all cancer types, with, for example, 5-year rectal cancer survival increasing more than 13 percentage points in Denmark, Ireland, and the UK. For 2010–14, survival was generally higher in Australia, Canada, and Norway than in New Zealand, Denmark, Ireland, and the UK. Over the study period, larger survival improvements were observed for patients younger than 75 years at diagnosis than those aged 75 years and older, and notably for cancers with a poor prognosis (ie, oesophagus, stomach, pancreas, and lung). Progress in cancer control (ie, increased survival, decreased mortality and incidence) over the study period was evident for stomach, colon, lung (in males), and ovarian cancer.

 

Interpretation

The joint evaluation of trends in incidence, mortality, and survival indicated progress in four of the seven studied cancers. Cancer survival continues to increase across high-income countries; however, international disparities persist. While truly valid comparisons require differences in registration practice, classification, and coding to be minimal, stage of disease at diagnosis, timely access to effective treatment, and the extent of comorbidity are likely the main determinants of patient outcomes. Future studies are needed to assess the impact of these factors to further our understanding of international disparities in cancer survival.

The full article is available from The Lancet 

See also:

Cancer Research Measuring up: how does the UK compare internationally on cancer survival?

BBC News Cancer survival in the UK improving, but lagging behind – study

Exercise training improves physical capacity after lung cancer surgery

NIHR | September 2019| Exercise training improves physical capacity after lung cancer surgery

A new NIHR Signal showcases the findings of a Cochrane update which reviewed eight trials which combined aerobic and resistance exercise after lung cancer surgery. Although the trials were small in terms of participants (450 participants in total), they demonstrated consistent and meaningful improvements in exercise capacity. 

Plain Language Summary

Exercise training after lung surgery for people with non‐small cell lung cancer

Review question

We updated the evidence about the effect of exercise training after lung surgery for non‐small cell lung cancer (NSCLC) on fitness level; adverse events; quality of life; strength of the leg, hand, and breathing muscles; breathlessness; fatigue; feelings of anxiety and depression; and lung function.

Background

After lung surgery for NSCLC, people’s fitness levels and quality of life decrease. We know that exercise training improves these outcomes in people with chronic lung disease and in those with prostate and breast cancer. In the 2013 version of this review, we demonstrated that exercise training improved fitness level (distance walked on the six‐minute walk test) in people after lung surgery for NSCLC. Due to the limited number of studies, the effect of exercise training on quality of life and other outcomes was unclear.

Search date

The evidence is current to February 2019.

Study characteristics

We included three studies from the 2013 review and an additional five new studies from the current review, for a total of eight studies with 450 participants (180 women). The number of participants in the included studies ranged between 17 and 131; the mean age of participants was between 63 and 71 years. Six studies explored the effects of combined aerobic and strengthening exercises; one explored the effects of combined aerobic exercise and inspiratory muscle training; and one explored the effects of combined aerobic exercise, strengthening exercise inspiratory muscle training and balance training. The length of the exercise programmes ranged from four to 20 weeks, with exercises performed twice to five days a week.

Key results

Our results showed that people with NSCLC who exercised after lung surgery had better fitness level (measured using both a cycling test and the six‐minute walk test) and strength in their leg muscles compared to those that did not exercise. We also showed initial evidence for better quality of life and less breathlessness in those who exercised. One adverse event (hip fracture) related to the intervention was reported in one study. The effect of exercise training after lung surgery on grip strength, fatigue, and lung function was uncertain. We found insufficient evidence for improvements in the strength of breathing muscles or feelings of anxiety and depression.

Quality of evidence

Overall the quality (certainty) of evidence for the outcomes was moderate, ranging between very low (for breathlessness) and high (for fitness level measured via the six‐minute walk test).

Full reference: Cavalheri, V. et al | 2019| Exercise training undertaken by people within 12 months of lung resection for non-small cell lung cancer | Cochrane Database Syst Rev|  Vol. 6 | doi/10.1002/14651858.CD009955.pub3/epdf/full

The full article is available to read from Cochrane 

Background: Decreased exercise capacity and health-related quality of life (HRQoL) are common in people following lung resection for non-small cell lung cancer (NSCLC). Exercise training has been demonstrated to confer gains in exercise capacity and HRQoL for people with a range of chronic conditions, including chronic obstructive pulmonary disease and heart failure, as well as in people with prostate and breast cancer. A programme of exercise training may also confer gains in these outcomes for people following lung resection for NSCLC. This systematic review updates our 2013 systematic review.

Objectives: The primary aim of this review was to determine the effects of exercise training on exercise capacity and adverse events in people following lung resection (with or without chemotherapy) for NSCLC. The secondary aims were to determine the effects of exercise training on other outcomes such as HRQoL, force-generating capacity of peripheral muscles, pressure-generating capacity of the respiratory muscles, dyspnoea and fatigue, feelings of anxiety and depression, lung function, and mortality.

Search Methods: We searched for additional randomised controlled trials (RCTs) in the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library 2019, Issue 2 of 12), MEDLINE (via PubMed) (2013 to February 2019), Embase (via Ovid) (2013 to February 2019), SciELO (The Scientific Electronic Library Online) (2013 to February 2019), and PEDro (Physiotherapy Evidence Database) (2013 to February 2019).

Selection Criteria: We included RCTs in which participants with NSCLC who underwent lung resection were allocated to receive either exercise training, which included aerobic exercise, resistance exercise, or a combination of both, or no exercise training.

Data collection and analysis: Two review authors screened the studies and identified those eligible for inclusion. We used either postintervention values (with their respective standard deviation (SD)) or mean changes (with their respective SD) in the meta-analyses that reported results as mean difference (MD). In meta-analyses that reported results as standardised mean difference (SMD), we placed studies that reported postintervention values and those that reported mean changes in separate subgroups. We assessed the certainty of evidence for each outcome by downgrading or upgrading the evidence according to GRADE criteria.

Main results: Along with the three RCTs included in the original version of this review (2013), we identified an additional five RCTs in this update, resulting in a total of eight RCTs involving 450 participants (180 (40%) females). The risk of selection bias in the included studies was low and the risk of performance bias high. Six studies explored the effects of combined aerobic and resistance training; one explored the effects of combined aerobic and inspiratory muscle training; and one explored the effects of combined aerobic, resistance, inspiratory muscle training and balance training. On completion of the intervention period, compared to the control group, exercise capacity expressed as the peak rate of oxygen uptake (VO2peak) and six-minute walk distance (6MWD) was greater in the intervention group (VO2peak: MD 2.97 mL/kg/min, 95% confidence interval (CI) 1.93 to 4.02 mL/kg/min, 4 studies, 135 participants, moderate-certainty evidence; 6MWD: MD 57 m, 95% CI 34 to 80 m, 5 studies, 182 participants, high-certainty evidence). One adverse event (hip fracture) related to the intervention was reported in one of the included studies. The intervention group also achieved greater improvements in the physical component of general HRQoL; improved force-generating capacity of the quadriceps muscle; and less dyspnoea. We observed uncertain effects on the mental component of general HRQoL, disease-specific HRQoL, handgrip force, fatigue, and lung function. There were insufficient data to comment on the effect of exercise training on maximal inspiratory and expiratory pressures and feelings of anxiety and depression. Mortality was not reported in the included studies.

Authors’ Conclusions: Exercise training increased exercise capacity and quadriceps muscle force of people following lung resection for NSCLC. Our findings also suggest improvements on the physical component score of general HRQoL and decreased dyspnoea. This systematic review emphasises the importance of exercise training as part of the postoperative management of people with NSCLC.

Full details from NIHR 

National Cancer Patient Experience Survey 2018

The survey is conducted on an annual basis and includes all adult patients (aged 16 and over), with a confirmed primary diagnosis of cancer, who have been admitted to hospital as inpatients for cancer related treatment, or who were seen as day case patients for cancer related treatment, and have been discharged between the months of April, May or June 2018.

Full resource: National Cancer Patient Experience Survey 2018 – National and Local data

 

Cancer overtakes CVD to become leading cause of death in high income countries

Mahase, E.| 2019|  Cancer overtakes CVD to become leading cause of death in high income countries| BMJ |366| l5368| https://www.bmj.com/content/366/bmj.l5368.full

Cancer is now responsible for twice as many deaths as cardiovascular disease (CVD) in high income countries, according to two new papers published in The Lancet.

The studies said that while CVD remains the leading cause of mortality among middle aged adults globally, accounting for 40% of all deaths, this is no longer the case in high income countries.

The researchers estimated that of 55 million deaths that occurred in the world in 2017, approximately 17.7 million were from CVD.

The findings come from the PURE study, a large prospective international cohort study that involves substantial data from a large number of middle, low, and high income countries.

Countries analysed in the two reports include: Argentina, Bangladesh, Brazil, Canada, Chile, China, Colombia, India, Iran, Malaysia, Pakistan, Palestine, Philippines, Poland, Saudi Arabia, South Africa, Sweden, Tanzania, Turkey, United Arab Emirates, and Zimbabwe (Source: BMJ).

The full story is available from the the BMJ 

These are the full-text journal articles featured in the The BMJ article:

Dagenais, G. R. | 2019| Variations in common diseases, hospital admissions, and deaths in middle-aged adults in 21 countries from five continents (PURE): a prospective cohort study | The Lancet | https://doi.org/10.1016/S0140-6736(19)32007-0

Summary

Background

To our knowledge, no previous study has prospectively documented the incidence of common diseases and related mortality in high-income countries (HICs), middle-income countries (MICs), and low-income countries (LICs) with standardised approaches. Such information is key to developing global and context-specific health strategies. In our analysis of the Prospective Urban Rural Epidemiology (PURE) study, we aimed to evaluate differences in the incidence of common diseases, related hospital admissions, and related mortality in a large contemporary cohort of adults from 21 HICs, MICs, and LICs across five continents by use of standardised approaches.

 

Methods

The PURE study is a prospective, population-based cohort study of individuals aged 35–70 years who have been enrolled from 21 countries across five continents. The key outcomes were the incidence of fatal and non-fatal cardiovascular diseases, cancers, injuries, respiratory diseases, and hospital admissions, and we calculated the age-standardised and sex-standardised incidence of these events per 1000 person-years.

 

Findings

This analysis assesses the incidence of events in 162 534 participants who were enrolled in the first two phases of the PURE core study, between Jan 6, 2005, and Dec 4, 2016, and who were assessed for a median of 9·5 years. During follow-up, 11 307 (7·0%) participants died, 9329 (5·7%) participants had cardiovascular disease, 5151 (3·2%) participants had a cancer, 4386 (2·7%) participants had injuries requiring hospital admission, 2911 (1·8%) participants had pneumonia, and 1830 (1·1%) participants had chronic obstructive pulmonary disease (COPD). Cardiovascular disease occurred more often in LICs (7·1 cases per 1000 person-years) and in MICs (6·8 cases per 1000 person-years) than in HICs (4·3 cases per 1000 person-years). However, incident cancers, injuries, COPD, and pneumonia were most common in HICs and least common in LICs. Overall mortality rates in LICs (13·3 deaths per 1000 person-years) were double those in MICs (6·9 deaths per 1000 person-years) and four times higher than in HICs (3·4 deaths per 1000 person-years). This pattern of the highest mortality in LICs and the lowest in HICs was observed for all causes of death except cancer, where mortality was similar across country income levels. Cardiovascular disease was the most common cause of deaths overall (40%) but accounted for only 23% of deaths in HICs ( vs 41% in MICs and 43% in LICs), despite more cardiovascular disease risk factors (as judged by INTERHEART risk scores) in HICs and the fewest such risk factors in LICs. The ratio of deaths from cardiovascular disease to those from cancer was 0·4 in HICs, 1·3 in MICs, and 3·0 in LICs, and four upper-MICs (Argentina, Chile, Turkey, and Poland) showed ratios similar to the HICs. Rates of first hospital admission and cardiovascular disease medication use were lowest in LICs and highest in HICs.

 

Interpretation

Among adults aged 35–70 years, cardiovascular disease is the major cause of mortality globally. However, in HICs and some upper-MICs, deaths from cancer are now more common than those from cardiovascular disease, indicating a transition in the predominant causes of deaths in middle-age. As cardiovascular disease decreases in many countries, mortality from cancer will probably become the leading cause of death. The high mortality in poorer countries is not related to risk factors, but it might be related to poorer access to health care.

Article available here

Yusuf, S. | 2019| Modifiable risk factors, cardiovascular disease, and mortality in 155 722 individuals from 21 high-income, middle-income, and low-income countries (PURE): a prospective cohort study | The Lancet | DOI:https://doi.org/10.1016/S0140-6736(19)32008-2

Summary

Background

Global estimates of the effect of common modifiable risk factors on cardiovascular disease and mortality are largely based on data from separate studies, using different methodologies. The Prospective Urban Rural Epidemiology (PURE) study overcomes these limitations by using similar methods to prospectively measure the effect of modifiable risk factors on cardiovascular disease and mortality across 21 countries (spanning five continents) grouped by different economic levels.

 

Methods

In this multinational, prospective cohort study, we examined associations for 14 potentially modifiable risk factors with mortality and cardiovascular disease in 155 722 participants without a prior history of cardiovascular disease from 21 high-income, middle-income, or low-income countries (HICs, MICs, or LICs). The primary outcomes for this paper were composites of cardiovascular disease events (defined as cardiovascular death, myocardial infarction, stroke, and heart failure) and mortality. We describe the prevalence, hazard ratios (HRs), and population-attributable fractions (PAFs) for cardiovascular disease and mortality associated with a cluster of behavioural factors (ie, tobacco use, alcohol, diet, physical activity, and sodium intake), metabolic factors (ie, lipids, blood pressure, diabetes, obesity), socioeconomic and psychosocial factors (ie, education, symptoms of depression), grip strength, and household and ambient pollution. Associations between risk factors and the outcomes were established using multivariable Cox frailty models and using PAFs for the entire cohort, and also by countries grouped by income level. Associations are presented as HRs and PAFs with 95% CIs.

 

Findings

Between Jan 6, 2005, and Dec 4, 2016, 155 722 participants were enrolled and followed up for measurement of risk factors. 17 249 (11·1%) participants were from HICs, 102 680 (65·9%) were from MICs, and 35 793 (23·0%) from LICs. Approximately 70% of cardiovascular disease cases and deaths in the overall study population were attributed to modifiable risk factors. Metabolic factors were the predominant risk factors for cardiovascular disease (41·2% of the PAF), with hypertension being the largest (22·3% of the PAF). As a cluster, behavioural risk factors contributed most to deaths (26·3% of the PAF), although the single largest risk factor was a low education level (12·5% of the PAF). Ambient air pollution was associated with 13·9% of the PAF for cardiovascular disease, although different statistical methods were used for this analysis. In MICs and LICs, household air pollution, poor diet, low education, and low grip strength had stronger effects on cardiovascular disease or mortality than in HICs.

 

Interpretation

Most cardiovascular disease cases and deaths can be attributed to a small number of common, modifiable risk factors. While some factors have extensive global effects (eg, hypertension and education), others (eg, household air pollution and poor diet) vary by a country’s economic level. Health policies should focus on risk factors that have the greatest effects on averting cardiovascular disease and death globally, with additional emphasis on risk factors of greatest importance in specific groups of countries.

Full article available from The Lancet