News and Views

Mortality rate after AMI higher for young women than young men

Sex differences to the disadvantage of women have been well documented in the treatment of cardiovascular disease. As recently as 2016 a statement from the American Heart Association, despite noting improvements in the previous decade, reported that such differences exist ‘in the presentation, pathophysiological mechanisms, and outcomes in patients with acute myocardial infarction’ (AMI). ¹ Indeed, this was the first ever statement from the AHA on heart disease in women, and it could at last record a ‘dramatic decline in mortality rates for women’ attributed to an increase in awareness, and a greater focus on women and cardiovascular disease risk.

Nevertheless, and despite such improved outcomes, a new study has still found that women who experienced a first infarction at a younger age (below 50) were less likely to receive coronary revascularisation or be treated with guideline-directed therapies. ² Moreover, although the young women who survived that first hospitalisation had similar cardiovascular mortality as men, their all-cause mortality was significantly worse.

The study, described as the largest ever to examine the sex differences in outcome in young AMI patients, was a pooled assessment of patients in two large US registries (404 women and 1693 men) with a median 11.2 year follow-up. The results showed that, even after adjustment for differences in risk factors and treatment, the women had a higher rate of long-term all-cause mortality, suggesting ‘an inherent excess risk in young women’. Post MI cardiovascular mortality rate was 4.4% in men and 5.3% in women. However, when hospital deaths were excluded, all-cause mortality rate was 9.5% in men and 13.5% in women, a statistically significant difference. Moreover, a greater proportion of women died from causes other than cardiovascular problems, 8.4% versus 5.4% respectively and a 1.6-fold increased risk of death.

Women were less likely to have coronary angiography (93.5% versus 96.7%) or coronary vascularisation (82.1% versus 92.6%). They were less likely to be discharged with aspirin (92.2% versus 95%), beta-blockers (86.6% versus 90.3%), ACE inhibitors or receptor blockers (53.4% versus 63.7%), and statins (82.4% versus 88.4%).

The investigators were at a loss to explain the gender discrepancies, but did note a protective effect of estrogen in the premenopausal years and the possibility that traditional cardiovascular risk factors such as smoking ‘may pose a greater influential risk for CV events in women than men’. An accompanying editorial in the European Heart Journal stressed the importance of addressing cardiovascular risk factors in young AMI patients, especially those with a high burden of comorbidities. However, non-traditional risk factors, such as a history of pre-eclampsia, gestational diabetes or ovarian surgery would also deserve attention, while adding that ‘young women with depression are six times more likely to have coronary heart disease than women without depression’. The editorial also noted, as this column has reported before, the dominant male bias in so many cardiovascular trials and the continuing need for ‘designing studies that account for sex differences; facilitating recruitment of women into clinical trials; requesting sex-based data when reviewing manuscripts; and reporting sex differences in published research’.

Mehta LS, Beckie TM, DeVon HA, et al. Acute myocardial infarction in women: a scientific statement from the American Heart Association. Circulation 2016; 133: 916–947.

Chocolate fails to demonstrate cancer protection in WHI observational study

Chocolate, like coffee and red wine, has long been on the lists of friends or foe in public health. Maybe yes, maybe no, but a definite maybe. The flavonoids in chocolate, especially dark chocolate with a high cocoa content, are known to be antioxidants and thus active against cellular damage from free radicals. Flavonoids have also gained recent recognition as possible anticancer agents, promoting cytotoxicity and apoptosis in cancer cells, and thus raising the hypothesis that cocoa and dark chocolate may reduce cancer risks. ¹

The theory of an inverse relationship between chocolate consumption and cancer risk has now been put to the everyday test by the observational data of the Women’s Health Initiative. ² The amount of chocolate consumption was assessed over a mean 14.8 year follow-up in the WHI’s food frequency questionnaire, which in this study had ‘plausible’ data from more than 100,000 of the WHI’s original subjects. Cancer risk, as confirmed by ‘physician adjudication, was than correlated with quartiles of chocolate consumption disclosed in the questionnaire. There was an overall cancer incidence rate of 17% over the study follow-up, but no statistically significant associations for total invasive cancer or invasive breast cancer in any of the chocolate quartiles. There was a small association with colorectal cancer, but this result, said the authors, ‘may be attributable to the excess adiposity associated with frequent chocolate candy consumption’.

Five years ago the same investigators using the same WHI observational cohort and food frequency questionnaire had found that those eating chocolate in varying amounts all experienced weight gain over a three-year study period. ³ Results showed that each additional 1 oz/day was associated with an average greater three‐year weight gain of 0.92 kg. The weight gain in each chocolate‐candy intake level increased as BMI increased above the normal range, and was inversely associated with age. Perhaps the weight gain from eating chocolate would cancel any benefit from its flavonoid content?

Romagnolo DF, Selmin OI. Flavonoids and cancer prevention: a review of the evidence. J Nutr Gerontol Geriatr 2012; 31: 206–238.

Intermittent fasting and the pursuit of weight loss

Far be it from this column to take a swipe at diets. Their faults seem to lie less with the diet itself than the person pursuing it. As Falstaff’s physician said of the great man’s urine sample, there’s nothing wrong with the sample, only with the man who provided it. ¹ Yet most weight-loss and balanced diets have an undeniable health benefit, especially in the prevention of chronic diseases. Evidence in favour of the Mediterranean diet’s role in the prevention of cardiovascular disease, for example, was described in a major review last year as ‘large, strong and consistent’. ² Similarly, the evidence seems strong that a weight-loss diet with exercise can prevent or even reverse type 2 diabetes. A much publicised study from The Lancet in 2018 found that primary care-led ‘weight management’ caused remission of type 2 diabetes in almost half of all overweight subjects. ³ ‘Remission of type 2 diabetes is a practical target for primary care,’ the report concluded.

One such weight loss diet which has attracted much interest over recent years – and much controversy over recent weeks – is ‘intermittent fasting’, an eating regime concentrated within a restricted time during the day. There has been discussion about the time length of the eating window but a recent study of intermittent fasting found that limiting food consumption to just ten hours a day encouraged weight loss and improved metabolic parameters, including blood pressure. ³ This was a small study, mainly including women who were taking statins and antihypertensives. However, added to this routine therapy, the intermittent fasting regime (12 weeks of food consumption ten hours a day and a fasting period of 14 hours) prompted an overall weight loss of 3.3 kg corresponding to a BMI reduction of 3%. Notably, the authors reported, study subjects were told not to check calories or to change their eating habits, but only to observe the fasting window.

Now, a new and bigger study – though no less controversial – has concluded that this increasingly popular dietary approach does not result in any greater weight loss than eating without timed restrictions. ⁵ This was a 12-week randomised trial which pitched one group instructed to eat three balanced meals per day, against another asked to eat as wished from 12.00 pm until 8.00 pm but completely abstain from caloric intake outside those times. The latter, said the authors, was a ‘real-world recommendation to free-living individuals’. At 12 weeks, those in the intermittent fasting group did show some weight loss from baseline, but importantly the difference in weight loss between the two groups was not significant – nor was it in secondary endpoint metabolic parameters.

The study has drawn much criticism, notably in its design - and in the effects of the everyday US diet. But it doesn’t really clear up the feasibility of a time-restricted diet. We should also stress that the major study from last year – from the Salk Institute in California – did achieve its weight loss and reduced metabolic measures in combination with medication. However, one of the investigators from this study did reportedly say that a consistent 10-hour permitted eating window ‘allows your body to rest and restore for 14 hours at night’ and to ‘optimize metabolism’. The investigators described time-restricted eating as ‘powerful lifestyle intervention’, with persuasive animal studies in support, as well as support from the American Heart Association and numerous prevention groups, usually as part of a broader lifestyle programme.

There seems no clear answer, and the study results beg the question of whether a simple regime of fewer calories and a bit more exercise might do the same job but without the controversy. And it’s worth noting that the Women’s Health Initiative no less, in its dietary modification trial reporting in July this year, amazingly found that postmenopausal women eating four meals a day had a higher risk of type 2 diabetes than those getting by on just one to three. ⁶