Is it time to recommend cardiovascular protection for all?

Throughout the life course of everyone, there is an accumulating risk of developing circulatory disease, which is accelerated by hypertension and exacerbated further by additional factors, such as diabetes and hyperlipidaemia. However, for reasons of safety and economics, primary preventive cardiovascular healthcare has focussed on targeting the hypertensive individuals who fall within the higher risk strata: the mantra chanted is based around numbers needed to treat to avoid a single event based upon robust trial evidence drawn from cardiovascular outcome studies that recruited high-risk individuals followed for a few years. The rationale for this clinical trial strategy is based upon an objective to test whether lowering blood pressure could save lives and prevent cardiovascular events within a reasonable experimental timeframe. The approach worked: active medication was shown to have an immediate impact upon the incidence of stroke, heart failure began to disappear and coronary artery disease rates slowed. Times are changing and, with them, the demands of our patients are evolving. Modern therapeutic agents available to lower blood pressure and lipids are well tolerated and inexpensive. An increasingly health conscious and internet-informed population is emerging, which wants to stay healthy and make individual proactive life choices. There is a plethora of pills that contain combinations of aspirin, statins and antihypertensive dugs in low doses. Theoretically, they could provide a preventive panacea. Is it time to forget the classifications of hypertension and hyperlipidaemia and empower the individual to take such therapy like they might a vitamin? Many individuals have decided for themselves already. The potential societal benefits are enormous and the reduction in healthcare costs could be more so. Can a persuasive case be made? We would argue that the evidence that has formed the bedrock of national and international guidelines does not exist for every member of our populations. How should 'experts' respond to the demand to put these efficacious agents into the public domain? In 1978, Kannel and Gordan [1] published 18 years of follow-up data from the Framingham Study. Males and females were classified into optimal (systolic 105 mmHg) and poor risk (systolic 195 mmHg) categories. Added to the poor-risk diabetes, a current smoking habit and hyperlipidaemia, and a male individual aged 35 years was found to have an 8-year probability of developing cardiovascular disease of 60%. This outstanding pioneering study opened our eyes to risk predicting and of course went pari passu with trials of treating these risk factors and the demonstration of dramatic improvements in outcome. This study highlights also how far we have come in the modern approach, we adopt in patient management: contemporary guidelines tell us to treat a blood pressure of 195 mmHg immediately and normalize it quickly. In order to provide a test of the null hypothesis promptly and within a feasible economic budget, of necessity treatment trials sought to recruit patients with established cardiovascular disease or at high risk of developing it. Invariably the outcome was positive. The evidence was overwhelmingly in favour of offering medication to lower high blood pressure and cholesterol. The question was asked whether treatment programmes could be extended to low-risk patients, both sexes and all ethnic backgrounds? These reservations have been allayed, and modern management appears inclusive [2]. However, despite clear evidence that an increase in cardiovascular risk is recognized at systolic pressures around 115 mmHg and increases as pressure rises, the clinical definition of high blood pressure is above 140 mmHg. In addition, a person needs to present with blood pressure readings consistently in excess of this level to be diagnosed as hypertensive and eligible for treatment. This scenario is evidence-based and reflects a historic concern about doing more harm than good. For example, the more patients treated the more side effects of drugs will be observed and the need to balance a realistic expectation of cardiovascular event reduction for what was a costly outlay on medication. The former can be partially dismissed with the proven safety profile of modern drugs, the latter by the arrival of generic formulations. The intrusion into the uncharted blood pressure range has been stimulated by recent trials demonstrating that treated to below 130 mmHg rather than the conventional target of 140 mmHg is associated with even more circulatory protection [3,4], and in the case of SPRINT, the study was stopped early because of benefit seen within just over 3 years [3]. But here we must pause and dissect the evidence further. The SPRINT Trial excluded certain patients: first it contained no people with diabetes and hypertension. This exclusion was intentional as people with diabetes had been tested for this same endpoint in the ACCORD Trial [5]. The outcome was regarded widely as providing no evidence for intensively treating blood pressure in these high-risk individuals. Of note, there was a significant reduction in stroke in the short time frame of a relatively underpowered study. We would add that an individual's cardiovascular risk is for a lifetime not just trial time: more benefit will likely accrue over a protracted treatment time in this chronic disease setting. Second people who had sustained a stroke were excluded because they were examined in the SPS3 Trial [6]. Here the further reduction in blood pressure was associated with a reduction in stroke, which was not significant. We would argue that to see a patient sustain a stroke in 2023 is a tragedy. and the onus on healthcare systems is to prevent the index event rather than recurrence. Hypertension is the most potent risk factor for the acceleration of cardiovascular risk. The case being advanced here is for considering primary preventive therapy at lower levels of blood pressure at younger age points in healthy individuals. The hope is that the age-related rise in pressure will be slowed and the effects on accelerated circulatory senescence attenuated. Critics of aggressive blood pressure control point out the significant increase in falls, hyperkalaemia and fall in glomerular filtration rate (GFR). None of these contributed to an excess mortality. Furthermore, these events were seen against a background of treating hypertension above 140 mmHg. Finally, SPRINT excluded frail patients and those in care homes. Earlier intervention holds promise to reduce events and thereby decrease morbidity and loss of independence. Guidelines are creeping slowly lower. The margins around the definition of hypertension are blurred further by HOPE-3 [7,8], which treated patients with a blood pressure of between 130 and 139 mmHg and an 'intermediate' risk profile with a statin and angiotensin receptor blocker/diuretic combination and demonstrated event reduction with Rosuvastatin but not with Candesartan plus hydrochlorothiazide given for a median follow-up of 5.6 years, although there was benefit in those with a blood pressure greater than 143.5 mmHg. Cushman and Goff [9] point out that neither of the antihypertensive drugs used has shown a reduction in events at such low doses and that meta-analyses of trials in adults with an average SBP higher than 130 mmHg and either clinical cardiovascular disease or a higher cardiovascular risk than recruited here (5%) do provide support for intervening [10]. If we accept 130 mmHg, we are just 15 mmHg above the threshold at which risk takes off in the population, although the individuals in HOPE-3 were not completely extrapolatable to the general community at large. There is overwhelming evidence now that women who develop preeclampsia have a four-fold risk of future incident heart failure and a two-fold increased risk of coronary heart disease, stroke and death because of coronary heart or cardiovascular disease. One might say this is predictable because preeclampsia is more often seen in patients who have obesity, diabetes or hypertension but many are not. This notwithstanding it is attractive to include these patients into early prevention programmes. More evidence is needed and soon, because this may be an area where physicians may wish to prescribe if trials are convincing. Another area for primary prevention is dementia. There are unequivocal data to suggest that the rate of dementia development is falling in western Europe and, almost certainly, this is because of cardiovascular disease prevention programmes. More than 70% of Alzheimer's disease has a vascular component, and there are multiple studies, which show that dementia rates rise in the higher levels of blood pressure. Also retrospective analyses of trials of the treatment of hypertension have shown that lowering pressure is associated with a slowing of cognitive decline and a reduction in dementia benefit. A properly powered trial in this area should be a priority. A subset of individuals is increasingly curious about their health. This translates into an insatiable need for information on how to stay well – the explosion of fitness (including high-intensity interval training) and interest in nutritional supplementation being just two examples of changing attitudes to modern lifestyle. The advent of polypills, which contain various agents such as aspirin, statins and antihypertensive drugs all in low doses offers another dimension to cardiovascular disease protection. The risk of side effects should be minimal –the risk of benefit is also unknown. Empowering the individual to make a life choice and embarking on a course of such medication brings blood pressure lowering for all a step closer. The expense could be offset by savings, which accrue from the reduction in treatment for stroke survivors, the fall in coronary revascularization procedures and dementia care needs. Those are the arguments that could be supported by evidence-based logic but individuals are not waiting for those research studies. Cheap nontoxic drugs are becoming a persuasive daily regime for people keen to stay healthy. We are left with a question of where to stand in the new and evolving setting of individual empowerment. How should we react? A subset of people is going to self-medicate or supplement with polypills, and our view is the risk of harm is low, and community benefit will likely follow. Notably, this new wave of demand exists in the context of underdiagnosis and undertreatment of hypertension, which remains a poorly addressed public health issue. The concept of a specific threshold for medical intervention for hypertension is being challenged in the public, as blood pressure is a continuous variable, and risk is enhanced above 115 mmHg. Is it time to consider societal benefit by allowing individuals to make choices for themselves? It is interesting to entertain that we could enter a new era of disease prevention, and the opportunity is there to grasp. Although we do not have the evidence base that justifies the current position on blood pressure guidelines in order to extend recommendations to the 'normotensive' population, should we discourage a self-informed internet-empowered body that sees self-monitoring and management of its risk factors as a priority? Those individuals have a robust point of view. If we can provide no further data because of funding reluctance, we have little choice but to creatively approach interfacing with our patients as they venture into uncharted territory. There are risks with having the populace set the medical intervention agenda. One is the medicalization of health – wellness with a medication is not the same as diet and physical activity. Other risks are the diversion from science and evidence-based treatment and the inability to track over-the-counter use to assess risk/benefit. However, by the latest guidance, 1.2 billion people across the globe have diagnosable hypertension, most not treated. Yes, perhaps we should give the health-conscious a pass to take their polypill while we focus on the urgency of management of blood pressure in the hypertensive range. ACKNOWLEDGEMENTS Conflicts of interest There are no conflicts of interest.