Blood pressure is a variable and quantitative trait, with a normal blood pressure defined as lower than 120/80 mmHg and hypertension defined when systolic blood pressure is higher than 140 mmHg and diastolic blood pressure is higher than 90 mmHg. These definitions are based in large part on blood pressure distribution and in the population and levels above which blood pressure-related cardiovascular and renal complications develop. Accordingly, major hypertension guidelines suggest that treatment targets should be lower than 140/90 mmHg 1–3.
However, the question arises whether 140/90 mmHg is in fact the optimal blood pressure to target because death from cardiovascular disease actually increases progressively and linearly as blood pressure increases above 115/75 mmHg. For every 20 mmHg increase in systolic blood pressure or 10 mmHg increase in diastolic blood pressure, there is a doubling of mortality from ischaemic heart disease and stroke in both men and women across age groups (40–89 years) 4. Thus, individuals with ‘high normal’ blood pressure are already at increased cardiovascular risk. Therefore, what blood pressure targets should we be striving for to reduce risk and to prevent cardiovascular disease in patients with hypertension? This question has recently been discussed and fiercely debated following the recent publication of a new trial, The Systolic Blood Pressure Intervention Trial (SPRINT), a multicentre, randomized, controlled, open-label trial, which tested the hypothesis that treating to a lower systolic blood pressure target (<120 mmHg) would reduce cardiovascular events more than treating to the standard target (140 mmHg) 5. Results showed that intensive treatment to lower than 120 mmHg was associated with a 25% reduction in primary composite outcomes and a 27% reduction in all-cause mortality compared with standard treatment, which achieved a systolic blood pressure of 136 mmHg. Supporting these results are data from large meta-analyses that also showed cardiovascular benefit when systolic blood pressure was targeted to levels lower than 130 mmHg 6–8. Hence, there is now compelling evidence that if systolic blood pressure is maintained at 120–130 mmHg rather than at the currently accepted level of lower than 140 mmHg, patients with hypertension will have less cardiovascular events and reduced morbidity and mortality 9,10.
Unfortunately, patients with diabetes, previous stroke or polycystic kidney disease were excluded from SPRINT and thus it remains unclear whether the pronounced beneficial effects observed in the intensively treated hypertensive cohort would have held true if patients with these conditions had also been included. As such, some caution should be exercised because SPRINT findings cannot be generalized and need to be considered in the context of the patient profile included in the trial.
Lowering the recommended treatment targets brings with it many practical issues, such as increased economic burden on already stressed healthcare systems and more intensive healthcare provision. In addition, there is the real challenge of actually achieving optimal targets. Let us consider the current status. On the basis of targets of 140/90 mmHg, ∼30% of the adult population has high blood pressure warranting treatment. Despite the availability of many classes of excellent antihypertensive drugs, control is suboptimal, with fewer than 30% of hypertensive patients receiving therapy and, of these, only about 15–20% are treated to target 11–13. This is a global phenomenon and in some regions, control rates are as low as 10%. The reasons for these poor statistics are complex and include multiple factors, such as poor compliance and adherence, lack of access to drugs, inappropriate therapies and lack of awareness among others 12,13. Now let us consider the situation if blood pressure targets are set at 120 or 130 mmHg; it is likely that more than 60% of the adult population globally would require treatment. On the basis of our current poor record of attaining an optimal target of 140 mmHg, the likelihood of achieving lower targets in the majority of our patients with hypertension is slim.
Hypertension is often associated with multiple comorbidities, including diabetes mellitus. Data from prospective cohort studies indicate that development of type 2 diabetes is almost 2.5 times higher in patients with hypertension compared with normotensive individuals 14 and that new-onset diabetes in patients with hypertension have a three times higher risk of cardiovascular disease 15. Much of the excess cardiovascular risk in diabetes is because of coexisting hypertension and, as such, hypertensive patients with coexisting diabetes have been classified as being at very high cardiovascular risk. Accordingly, many guidelines have suggested lower blood pressure targets than 140/90 mmHg in patients with diabetes and hypertension, with some recommending targets of 130–135/80–85 1–3,16–19. Interestingly, these recommendations have been made despite little evidence supporting this. In fact, the Action to Control Cardiovascular Risk in Diabetes study 20 did not find a significant reduction in cardiovascular events when systolic blood pressure was lowered to levels lower than 120 mmHg compared with targets of 133 mmHg. Similar conclusions were drawn from other large studies that examined blood pressure lowering in patients with diabetes. In an analysis of 49 trials comprising over 74 000 individuals, there was an improvement in cardiovascular mortality and morbidity when baseline systolic blood pressure was higher than 140 mmHg 21. However, for baseline blood pressure below 140 mmHg, additional antihypertensive treatment increased cardiovascular mortality, suggesting a J-type phenomenon of blood pressure lowering in patients with diabetes mellitus 22. Taken together, it seems that unlike nondiabetic hypertensive ‘SPRINT’ patients who benefit from blood pressure lowering to lower than 130 mmHg, hypertensive patients with diabetes gain cardiovascular benefits when systolic blood pressure is higher than 140 mmHg. Unravelling the reasons and mechanisms for these apparent divergent outcomes will require intensive research.
The current issue of the journal focuses on hypertension in type 2 diabetes, with an emphasis on optimal management. Some new insights related to vascular phenotypes (premature vascular ageing) in diabetes and hypertension are discussed, antihypertensive effects of antidiabetic drugs are introduced and the controversy on blood pressure targets in patients with diabetes and hypertension is debated. This comprehensive issue provides a compendium of important topics that underpin the link between diabetes, hypertension and cardiovascular disease, common comorbidities that are often challenging to manage in the clinic.
Conflicts of interest
There are no conflicts of interest.
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