Summary: optimal systolic BP is 129, BP drugs don’t promote longevity.
(I am not endorsing this post, I am posting it for comment.)
https://x.com/DrPaulMason/status/1883855381392506924
Here is a summary on ‘Blood Pressure, longevity and drugs’ I have composed for my patients. My conclusions might surprise you.
‘Blood Pressure, Longevity and Drugs’
High blood pressure (hypertension) is a well-known risk factor for early death. The belief that lowering blood pressure can lead to an increase in life expectancy has driven Australians to spend over $1.2 billion annually on blood pressure medications. However, while these drugs lower blood pressure, they don’t address the most common root cause of hypertension, which is insulin resistance. As a result, the expected longevity associated with a particular blood pressure may well be different in unmedicated and medicated individuals.
What’s the Ideal Blood Pressure for longevity?
Studies assessing the association between blood pressure and mortality often has significant limitations. These studies are often conducted in developed countries on high-risk populations. This means that many study subjects are likely to be taking blood pressure medications, limiting the generalisability of findings to unmedicated populations. Additionally, the number of very elderly participants in these studies is typically limited, restricting the ability of these studies to inform us about blood pressure and optimal longevity.
One study, published in BMJ in 2018, addresses these limitations and is the most methodologically sound study I have found on this topic. This was a prospective longitudinal study of 4,658 elderly Chinese individuals with an average age of 92 years (including 825 centenarians). Given the impressive age of the subjects, this study has the potential to inform us of optimal blood pressure for longevity.
There are two numbers in a standard blood pressure reading. The top number refers to systolic blood pressure (SBP) and indicates pressure when the heart pumps. The bottom number refers to diastolic blood pressure (DBP), which is the pressure when the heart relaxes between beats.
Systolic blood pressure (the top number reflecting peak pressure when the heart pumps) was shown by this study to predict longevity, with an optimal reading being 129 mmHg. Systolic blood pressures both below and above this level were found to represent an increased mortality risk, though this was not significant between about 120 mmHg and 140 mmHg. Importantly, the risk of premature mortality was greater for lower blood pressures than for higher blood pressures.
Diastolic blood pressure (bottom number, reflection pressure when the heart is relaxed), was shown to be all but worthless when it comes to predicting longevity. All-cause mortality was basically identical across a wide range of diastolic blood pressure (40 mmHg to 130 mmHg).# In essence, it is reasonable to only consider systolic blood pressure (the top number) when predicting longevity based on blood pressure**.
These findings have been replicated in other populations too. A UK-based study of females over the age of 80 had broadly similar findings, identifying the lowest risk of mortality when systolic blood pressure was between 120 to 139 mmHg. Another study of 68,901 Korean adults over the age of 65 found that the optimal systolic blood pressure in terms of mortality was 130-139 mmHg. In summary, the optimal systolic blood pressure for longevity in an unmedicated population is likely to be around 130 mmHg, with diastolic blood pressure being all but irrelevant.
Does Treating High Blood Pressure with Drugs Increase Life Expectancy?
Perhaps the most influential clinical guidelines on the management of blood pressure in Australia were published by the Australian Heart Foundation in 2016. Angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), calcium channel blockers, and thiazide-type diuretics are all recommended as first-line management for hypertension. Despite the strong recommendation to use these drugs for hypertension, on balance, there is no compelling evidence that taking blood pressure medications for hypertension increases life expectancy. This was demonstrated by a 2017 meta-analysis of 74 individual trials involving over 300,000 patients, which found no evidence that treating hypertension, even when systolic pressures were over 160 mmHg, offered any mortality benefit. Of course, it may be argued that some classes of medication may be superior to others, offering benefits through mechanisms independent of their blood-lowering effect. There is little compelling evidence, however, that any of the four classes of medication commonly initiated for hypertension offer mortality benefit.
A Closer Look at Specific Drug Classes:
ACE Inhibitors A 2014 meta-analysis published in JAMA examined these drug classes in patients with diabetes. Nine out of 11 studies on ACE inhibitors (e.g., Ramipril, Perindopril) found no benefit. The two outliers were industry-funded, with significant methodological limitations. One of these outliers was not in fact a new study, but rather a ‘re-analysis’ of existing trial data from a previous study which just so happened to come to a different conclusion. The other outlier was the ADVANCE trial which also had major methodological limitations. One of these was the use of a run in period (commonly seen in statin trials). Before the study officially started, every eligible subject received the active medications for 6 weeks. If they had any side effects to the drugs, they were removed from eligibility before the study even started (~14% of subjects who registered for the trial ultimately did not take part in the study). Of course, subjects removed during the run-in period were not included in adverse event data.
Consequently, practices such as this load the deck in favour of the drug intervention, leading to an overestimation of the net benefits. Further, these studies were on diabetics, and thus not applicable to the general population. Without these two industry funded outlier studies, the marginal benefit found by this meta-analysis for ACE inhibitors in terms of all cause mortality all but evaporates.
ARBs A 2014 meta-analysis published in JAMA examined these drug classes in patients with diabetes. Seven individual studies assessed Angiotensin II Receptor Blockers (e.g., Candesartan, Irbesartan, Losartan, Olmesartan, Telmisartan, Valsartan), with none finding a mortality benefit.
Calcium Channel Blockers
Calcium channel blockers are another class of medication often used for the management of hypertension. One of the earliest drugs in this class was nifedipine, which was introduced into the Australian market in the 1980’s. The immediate-release formulation of nifedipine was discontinued in Australia in October 2020 after it was found to significantly increase the risk of death in patients with heart disease by 2-3 times. Slow release nifedipine remains available, and is often prescribed to lower blood pressure. Despite this, I could not locate any research finding nifedipine to offer benefit when compared to ‘no treatment at all’ in terms of mortality. Most randomised controlled trials compared nifedipine against other blood pressure drugs rather than placebo, meaning can’t tell us whether nifedipine is superior to ‘no treatment at all’. The only randomised controlled trial that I could find comparing nifedipine against a placebo in the treatment of hypertension, the ‘Systolic Hypertension in Europe trial’ found there to be no mortality benefit. & Similarly, there is no evidence of mortality benefit compared to placebo for other calcium channel blockers, including amlodipine, felodipine and lercanidpine.
Thiazide diuretics
As with other blood pressure lowering medications, there is little if any evidence that thiazide type diuretics (eg. hydro-chlorothiazide) and thiazide ‘like’ diuretics (eg. indapamide) improve longevity when used to treat hypertension. This was demonstrated by a 2015 meta-analysis and systematic review of 21 studies which failed to find any mortality benefit of either thiazide-type or thiazide-like diuretics when compared to placebo.
Conclusion
In summary, the use of blood pressure medications appears to offer no compelling mortality benefit. Most studies compare drugs against each other rather than placebo, creating an illusion of benefit. Additionally, non-inferiority trials—where a new drug is compared against an older drug—often perpetuate the recommendation of multiple drugs without clear evidence of efficacy. Medications are simply no substitute for addressing the underlying causes of hypertension. Focusing on improving diet, exercise, and overall metabolic health offers a more effective and sustainable path to longevity and well-being.
It’s worth noting that the systolic blood pressure found to be optimal for longevity, 129 mmHg, is a level the American Heart Association considers to represent elevated blood pressure. Indeed, it is just shy of the 130 mmHg threshold which is considered stage 1 hypertension. That the optimal blood pressure for longevity as identified by this study is considered to represent elevated blood pressure ought to have us rethinking our blood pressure goals.
Importantly, this study also looked at whether or not study participants were taking medications for blood pressure and found these findings to be independent of medication status. There is another measure called ‘pulse pressure,’ which is the difference between SBP and DBP (SBP - DBP = pulse pressure). Being derived from both systolic blood pressure and diastolic blood pressure, the predictive value of pulse pressure was found to be midway between the two (inferior to the simpler systolic blood pressure). This study also found that blood pressures below 120 mmHg were more common in the last three months of life (despite the absence of any medication changes), with blood pressures below 110 mmHg being associated with the highest risk of all.