Abstract
Almost half the world’s population now ‘hypertensive’
There were many raised eyebrows in November last year when updated guidelines from the American College of Cardiology (ACC) and American Heart Association (AHA) lowered the threshold for defining hypertension to 130 mmHg systolic blood pressure (BP) and 80 mmHg diastolic. 1 In the USA the changes seemed welcomed by specialists, but challenged by some family doctors, who argued that ‘hypertensives’ currently managed by lifestyle measures would now need prescription medication – and many more formerly below the threshold would be reclassified as hypertensive.
In the few months since these updated guidelines were published, there have already been several studies forecasting an eruption of hypertension. In January, a report in the Journal of the American College of Cardiology (some of whose authors were also contributors to the new ACC/AHA guidelines) concluded that the guideline will result ‘in a substantial increase in the prevalence of hypertension, a small increase in the percentage of U.S. adults recommended for antihypertensive medication, and more intensive BP lowering for many adults taking antihypertensive medication’. 2 A more recent study, which included prevalence rates in developing countries, has even concluded that ‘almost half the world’s population is now hypertensive’ and within the range of the new diagnosis.3
In Britain, the definition and management of hypertension remain subject to the NICE (National Institute for Health and Care Excellence) guidance of 2011, which according to reports is scheduled for update in 2019. Currently, NICE defines ‘Stage 1 hypertension’ as clinic BP of 140/90 mmHg or higher and daytime average or home BP as 135/85 mmHg or higher, and ‘Stage 2’ as 150/95 mmHg or higher. NICE also advises that doctors should ‘offer antihypertensive drug treatment to people of any age’ with Stage 2 hypertension.
NICE makes little distinction between men and women, other than in its specific guidelines on hypertension in pregnancy. However, studies do show with some certainty that women before the menopause have a lower risk and incidence of hypertension than age-matched men; after the menopause, this advantage gradually disappears until, from the age of 65 onwards, a higher proportion of women than men have hypertension. A review in 2012 concluded that ageing of world population and longer life expectancies in women were ‘possibly related to the greater increases in the prevalence of hypertension among women’. 4
In March this year the Pharmaceutical Journal reported that NICE in its updated recommendations for 2019 would ‘almost certainly’ consider the evidence used in the 2017 ACC/AHA guidelines. But, added the PJ, NICE would not speculate ‘about how many people, if any, might be or might not be classed as hypertensive or offered anti-hypertensives’. One of the major contributors to the ACC/AHA guidelines was the NIH-sponsored SPRINT trial, which showed, in a study population aged 50 or over, that intensive BP control to a systolic level of <120 mmHg results in significantly greater cardiovascular benefit than with routine BP control to <140 mmHg. 5
References
Testosterone and CVD risk in postmenopausal women
There are few long-term studies of hormones in menopausal women whose progress was not scuppered by the Women’s Health Initiative. However, the Multi-Ethnic Study of Atherosclerosis (MESA), a study of the risk factors that predict progression to clinically overt cardiovascular disease, marches on, following up a cohort whose first baseline blood measurements were taken in 2000–2002. The latest report from the MESA study assesses the effect of endogenous sex hormones on cardiovascular disease (CVD) risk in almost 3000 postmenopausal women whose levels of testosterone, estradiol, dehydroepiandrosterone and sex hormone binding globulin (SHBG) were measured at the outset. 1
After 12 years of follow-up results showed that a higher testosterone/estradiol ratio was associated with a statistically significant elevated risk for incident CVD, coronary heart disease and heart failure. However, while higher levels of testosterone were associated with statistically significant increased CVD and coronary heart disease, higher estradiol levels – as expected – were associated with a lower coronary heart disease risk. Dehydroepiandrosterone and SHBG levels were not associated with these outcomes.
What emerged from the findings was not so much that estradiol – whose levels plummet after the menopause – is associated with a cardioprotective effect, but that any added CVD risk after the menopause seems particularly associated with testosterone. ‘There has been so much focus on estrogen being protective, but it may be that testosterone is toxic,’ said study author Erin Michos from Johns Hopkins School of Medicine, USA, ‘which might explain why men get heart disease earlier than women.’
However, Michos also noted that the ratio of testosterone to estradiol is not routinely calculated and, even if it were, ‘until we know what to do about the levels, I don’t think it’s quite ready for prime time’.
Despite the commonsense association of lower estradiol levels with a higher CVD risk, the authors nevertheless propose that the association of sex hormones with CVD events in postmenopausal women ‘is still unclear’ – and the best strategy to modify sex hormone levels to affect CVD risk ‘still uncertain’. Nevertheless, they add, ‘a more androgenic sex hormone profile may identify a woman at higher risk for CVD who may benefit from other risk-reducing strategies’.
Reference
Mediterranean diet back on the menu
Those who have turned to olive oil, nuts, fruit and a little red wine may have been influenced indirectly (or even directly) by the PREDIMED study, a large 2013 trial from Spain which found that a Mediterranean diet was more effective than a low-fat diet in the prevention of cardiovascular disease. 1 This was a huge trial which randomised 7447 subjects at high cardiovascular risk (but with no CVD) to a low-fat control diet or a Mediterranean diet supplemented with extra virgin olive oil or mixed nuts. After 4.8 years, the risk of major cardiovascular events was 30% lower in the combined Mediterranean groups than in the control diet group. Risk reductions were even greater in the two supplement groups. Results, as reflected in citations, were said to be ‘hugely impactful’.
Therefore, there was something of a shock when the trial’s initial publisher, New England Journal of Medicine no less, in June retracted the original 2013 study report after questions were raised over the validity of some baseline data. But the shock proved short-lived; the NEJM republished a revised version of the study at the same time as the retraction – and, for the many believers in the benefits of a Mediterranean diet, the cardiovascular pluses are just as great in the revised paper as in the retracted.
Behind the retraction – and that of studies in several other major journals – lies an anaesthesiologist from Torquay who through a complex computer model found that the baseline ‘random’ allocation of subjects to different treatments may not in fact be random at all. Thus, in the case of the PREDIMED study and according to the journal Science, a months-long inquiry by the Spanish researchers and NEJM staff uncovered that up to 1588 people in the trial hadn’t been properly randomized: Some were assigned to the same diet as someone else in their household... others, who lived in a rural area, were assigned to different diets based on the clinic closest to them...
Not yet similarly rehabilitated, however, after several severe shocks in 2018 are dietary supplements, especially those again hoping to have a place in the prevention of CVD. First, a systematic review from the National Health and Nutrition Survey in the USA found that none of the four most commonly used supplements – multivitamins, vitamin D, calcium and vitamin C – had any significant effect on CVD outcomes or all-cause mortality. 2 Indeed, vitamin D, the most studied nutrient, with 43 randomised trials evaluated, ‘convincingly’ showed a lack of harm or benefit. The only exception was folic acid, which appeared to reduce the risk for stroke.
And more recently still a Cochrane review commissioned by the WHO to assess the effects of polyunsaturated fats on health found that omega-3 fatty acids had little or no effect on all-cause or cardiovascular mortality when compared with placebo or usual diet. 3 The main types of omega-3 fats are alpha-linolenic acid, a fat found in plant foods, eicosapentaenoic acid and docosahexaenoic acid, both found in fish, and ‘there is a common belief’, said the Cochrane reviewers, ‘that eating more fish or taking omega-3 supplements reduces our risk of heart disease, stroke and death’.
They add that this analysis is ‘the most extensive systematic assessment of effects of omega-3 fats on cardiovascular health to date’, with more than 112,000 subjects studied, but the best quality evidence nevertheless suggests that increasing levels of omega-3s – despite lowering triglycerides and raising high density lipoprotein (HDL) levels – has little or no effect on mortality or cardiovascular health.
Commenting on the study, investigator Lee Hooper from the Norwich Medical School said: We got very excited by omega-3 fats in the early 1990s, following a couple of surprising and very positive trials. The results in later trials have never been as positive, but somehow we owned the notion that omega-3 fats were great for us, despite disappointing results ever since. I would love to see omega-3 supplements delivering — what a simple way to reduce our cardiovascular risk. But they don't, so we need to focus on the lifestyle interventions that do work — eating a high-quality diet, moderate alcohol, not smoking, and keeping fit and active.