Medicine
High blood pressure: the myth of low-sodium diets, antihypertensive drugs, and mortality
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MPH, MSc
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In this critical review, we address the management of hypertension and the relationship between blood pressure, low-sodium diet, antihypertensive medication, and mortality. We will see that everything is much less clear than is often assumed, given that cardiovascular risk is broader than hypertension, and hypertension is in turn determined by other cardiovascular risk factors, such as insulin resistance, etc. For this reason, blood pressure management is inadequate in most cases, and the approach that needs to be improved is cardiovascular risk, not simply reducing numbers with drugs, thereby ignoring the metabolic health that causes hypertension in the first place. We will see that diet cannot be thought of simply as sodium reduction. Additionally, when sodium in the body is severely reduced, there may be problems that have not been sufficiently assessed.
The answer is provided by comparative clinical trials such as that by Filippou et al, which shows that a Mediterranean diet with sodium restriction achieves a greater reduction in systolic blood pressure than the DASH diet and than sodium restriction alone in adults with grade 1 hypertension or high blood pressure. This shows that there are dietary elements that may be as important as or more important than sodium restriction. The Mediterranean diet with extra virgin olive oil, high in polyphenols and antioxidants that exert vasodilator effects, rich in anti-inflammatories and antioxidants, improves endothelial function and reduces vascular resistance. The intake of certain minerals with food (magnesium, potassium, and calcium) may also have contributed. For example, higher levels of circulating magnesium are inversely related to hypertension (Tirani et al 2025), with a relevant odds ratio (OR = 0.65).
However, the issue is to document reductions in absolute mortality, not to maximize reductions in blood pressure. A Cochrane systematic review evaluated the long-term effects of dietary salt reduction on mortality and cardiovascular events by analyzing eight randomized controlled trials (RCTs) with more than 7,000 people and follow-ups over several years. No solid evidence of a reduction in all-cause mortality was found in normotensive or hypertensive populations, although there is a trend toward a reduction in cardiovascular mortality and cardiovascular events in hypertensive individuals. These reductions in events were mainly driven by one high-weight trial, so the certainty of the evidence is low (Adler et al 2014), showing that there are very few controlled studies, despite this being a widely applied recommendation.
Recent systematic reviews and meta-analyses show that adherence to DASH-type diets reduces all-cause mortality, cardiovascular disease, and cancer (Soltani et al, 2020). However, the question is whether the reduction in mortality is due to sodium reduction or to an overall improvement in diet quality.
People's sensitivity to salt differs markedly, so an individual's blood pressure responds differently to changes in sodium intake. Interestingly, salt sensitivity itself is an independent risk factor for cardiovascular morbidity and mortality in both hypertensive and normotensive populations. Some studies have found that salt sensitivity is a risk factor that increases mortality, independently of blood pressure and even salt intake (Weinberger et al, 2001). In other words, negative vascular responses can occur even in the absence of hypertension and even when adjusting for salt consumption, with Mendelian randomization studies reinforcing this finding.
At the pharmacological level, the picture is mixed. In people under 60 years of age, there is no clear evidence of absolute decreases in mortality with antihypertensive drug treatment (Musini et al 2017). Another Cochrane systematic review of controlled studies has shown no clear evidence of decreases in mortality in people with mild hypertension (Diao et al, 2012). However, reductions in absolute mortality have been found in people over 60 years of age with moderate and severe hypertension (Musini et al 2019), showing a significant reduction in total mortality, cardiovascular mortality, and cerebrovascular mortality. However, the probabilities must be understood. There is an absolute risk reduction of 10 deaths per 1,000 participants (110 per 1,000 vs. 100 per 1,000 in the treatment group) over an average duration of 3.8 years. That is, an approximate reduction in mortality of 1 death per 100 drug treatments during that time. Additionally, the effect of the medication is limited by age. In people aged 80 years or older, a reduction in cardiovascular events was observed, but there was no significant decrease in total mortality (Musini et al, 2019). It is intuitive that, after a certain age, the increased likelihood of adverse effects (falls, orthostatic hypotension, interactions) becomes more significant, counteracting the possible cardiovascular benefits of the medication.
Nursing home residents are particularly prone to falls due to age-related physiological changes (e.g., blood pooling in the veins, decreased cardiac output, decreased baroreceptor sensitivity), as well as a higher prevalence of osteoporosis, limited mobility, cognitive impairment, polypharmacy, frailty, etc. Orthostatic hypotension, a trigger for falls and fractures, is a common complication of antihypertensive treatment, with the highest risk in the period immediately after treatment initiation. In a large cohort, the fracture incidence rate (per 100 person-years) in the antihypertensive group was 5.4 compared with 2.2 in the control group (adjusted HR 2.42). The number of falls decreased over the months of follow-up but remained high at 90 days. The findings suggest that initiation of antihypertensive medication is associated with an increased risk of fracture in older nursing home residents, emphasizing the need for caution when initiating therapy, especially in the high-risk period after starting the medication (Dave et al 2024).
Another way to look at the impact of antihypertensive medication is through drug withdrawal (deprescribing) studies. The efficacy and safety of deprescribing antihypertensive drugs has been evaluated through a synthesis of recent randomized clinical trials (Crisafulli et al, 2021). Only two studies meeting the inclusion criteria were identified. The first included patients aged 80 years and older with blood pressure <150 mmHg treated with at least two antihypertensive drugs for at least one year, and found no significant differences in blood pressure, quality of life, frailty, or adverse events after a reduction in medication at 12 weeks. The second study included adults aged 40 to 70 years without cardiovascular disease and demonstrated non-inferiority of deprescribing in the 10-year cardiovascular risk SCORE, although with a slight increase in systolic and diastolic blood pressure. Recent Cochrane systematic reviews on deprescribing in older adults show no significant effects on mortality (Gnjidic et al., 2025), although uncertainty is high due to the low number of studies conducted, so interpretation requires caution.
Jing et al., 2024 evaluated the effects of deprescribing antihypertensive medications on cognitive function in more than 12,000 nursing home residents over the age of 65 (Jing et al, 2024). The results showed that the intervention group undergoing deprescribing was associated with a lower probability of cognitive decline. Among patients with dementia, this reduction was even greater, suggesting that there may be a more pronounced benefit in people with compromised neurological health. The study highlights the complex relationship between blood pressure and neurological health in older people, given that hypertension is a risk factor for cognitive decline on the one hand, but also that the use of antihypertensive drugs can have negative effects on the functionality of vascular perfusion in the brain. Therefore, prescribing in older people should be done in a less generalized manner, carefully balancing the individual risk profile.
These findings reinforce the need to periodically reassess the indication for antihypertensive drugs in contexts of polypharmacy, polypathology, and low absolute risk (younger people, lower blood pressure, etc.). Therefore, an assessment of drug use and other ways of managing hypertension beyond simply resorting to medication is key, as reducing the pharmacological burden could prevent the progression to frailty and adverse and fatal clinical events in older people, and move away from comprehensive non-pharmacological approaches in younger people.
The fact that the impact of sodium reductions is not so clearly evident in absolute mortality may be due in part to disturbances in cellular ionic, hormonal, and metabolic balance, compromising the electrochemical gradient necessary for the myocardium and other organs, as well as increasing sympathetic stress through compensatory effects that may amplify the proarrhythmic environment to some extent. This elevates renin/angiotensin II/aldosterone and catecholamines, increasing vasoconstriction and afterload, and may elevate heart rate due to increased sympathetic tone. In the longer term, this neurohormonal activation could promote structural remodeling (hypertrophy/fibrosis) and increased myocardial excitability. Aldosterone, on the other hand, increases potassium (and sometimes magnesium) excretion, which may cause prolongation/dispersion of repolarization, in addition to ionic alterations through Na+/Ca2+ exchange and channels involved in the action potential.
Another relevant aspect is the reduced response to sodium restrictions associated with age. Filippou's study shows a cutoff point at 50 years of age. With age, arterial baroreceptor sensitivity decreases and arteries tend to become stiffer, which reduces the hemodynamic response to changes in extracellular volume or sympathetic tone, decreasing functional adaptations and the ability to induce vasodilation in this context. Aging is associated with progressive deterioration in renal function, which alters sodium excretion capacity and sensitivity to its reduction. In addition, this can alter the balance of the renin-angiotensin-aldosterone system (RAAS), activating it more strongly in a compensatory manner, limiting the net effect on blood pressure. Sarcopenia and negative body changes affect extracellular volume, also worsening homeostasis. Medication may have modulated the sodium system, reducing the margin for additional effect from diet. Inflammatory cytokines and reactive oxygen species produced by poor metabolic health and changes in body composition promote endothelial dysfunction, reduce the bioavailability of nitric oxide, and reduce the vasodilator response. Additionally, renal aging involves loss of functional nephrons and tubular atrophy, increasing vulnerability to electrolyte imbalances and inducing neurohormonal activation that may respond to low sodium load as if the body were in hypovolemia or threatened with dehydration, perpetuating proinflammatory and proarrhythmic hormonal signals.
In short, it is clear that simply reducing salt is a simplistic approach that, once again, is based on a reductionist line of reasoning that prioritizes the part over the whole. The response to sodium reduction is compromised with age, and perhaps chronic sodium restriction itself could produce some metabolic and electrolyte alterations that have been little considered, clinging to blood pressure figures. However, the balance between the potentially positive and potentially negative effects we are discussing is undoubtedly complex, so the definitive answer must come from controlled clinical trials that yield results on hard markers in various populations and subgroups. Surprisingly, despite the fact that it critically affects millions of people, these studies have not yet been sufficiently conducted, even though only a controlled empirical evaluation can fully clarify this issue. All in all, the dietary approach for most people should avoid being reduced simply to sodium restriction and should focus primarily on improving the quality of the foods included. Based on an initial response, a more specific clinical nutrition approach covering different aspects can be considered.
With an intermediate level of risk in people with different comorbidities, studies on composite outcomes conducted with thousands of people fail to show benefits, except perhaps in cardiovascular events in subgroups with higher blood pressure > 140 mmHg (Lonn et al, 2016). Even in people with comorbidities, there are not many studies that provide absolute mortality data. Those that do (Elgendy et al, 2016) are not well-controlled studies, which causes many problems in their interpretation. On the one hand, people who achieve better blood pressure readings may be more responsible and have made greater lifestyle changes, have a better baseline prognosis, etc., so the pharmacological effect is confounded. Blood pressure itself is also confounded, as it may indicate systemic deterioration, frailty, polypharmacy, etc., rather than good health. Therefore, the effect on mortality of the different blood pressure ranges achieved is also confounded.
Many physicians actually initiate treatments justified by the presence of some criterion considered a risk factor (often questionable), with a "preventive" consideration problematically assumed by poor probabilistic reasoning that fails to see the prior probability and to adequately weigh the probability of non-event in the Bayesian calculation (NPV, P(¬E)).
Many of the current international clinical guidelines raise central problems, guiding the treatment of high blood pressure outside the context of metabolic health and underlying vascular health. At the nutritional level, most guidelines focus on sodium reduction, with poor study of nutritional aspects by all of them. Blood pressure figures are better focused in some guidelines than in others in terms of the target population. Other guidelines, such as those of the AHA and AMA in the US, suggest medicalizing virtually the entire living population, to no one's surprise.
https://targetbp.org/
Drug treatment in low-risk groups not only appears to be an ineffective intervention, but may even increase mortality, according to some studies. Cochrane meta-analyses themselves highlight the absence of consistent reductions in absolute mortality, which calls into question the strategy of preventively medicating the majority of the population, except for those clearly justified by a high risk profile.
The European ESC guidelines make some mention of the conflicting evidence on salt. That's something, at least. However, they practically avoid talking about nutrition.
https://www.escardio.org/Guidelines/Clinical-Practice-Guidelines/El...
NICE also fails.
https://www.nice.org.uk/guidance/ng136/resources/hypertension-in-ad...
In short, the guidelines present a biased view of hypertension, with a biochemical theoretical basis that selects only those factors that lead to its medicalization, something that can hardly be considered an innocent oversight. This is even more so given that the evidence continues to raise considerable doubts. The nutritional approach demedicalizes people, and is therefore a threat to a system that moves a lot of money. The number to be treated at the individual level is high, so the patient must understand that cardiovascular risk still exists even if a drug lowers blood pressure (or lipid levels, etc.). We therefore criticize the reductionism of a medicalized approach to hypertension, when there are multiple mechanisms involved in the regulation of blood pressure and vascular function: autonomic balance, endothelial function, arterial stiffness, low-grade systemic inflammation, gut microbiota, and insulin resistance, among many others.
If you want to moderate your salt intake, reducing ultra-processed foods is a good start. But just as important, if not more so, than reducing numbers is staying active, eating a diet high in a variety of vegetables and fruits (not just the usual ones, but also berries, etc.), consuming virgin olive oil daily, etc. The mortality benefit observed with the DASH pattern may derive more from the overall improvement in the inflammatory, antioxidant, and vasomodulatory profile of the diet than from a linear reduction in sodium. There is nothing special about the "DASH diet" or "Mediterranean diet" except for the foods they contain, particularly vegetables, etc. What should be clear is that in most cases, the main issue is not blood pressure numbers, but metabolic health. Moreover, the former is primarily a consequence of the latter. It is not enough to say "eat better" when the doctor himself does not understand what that means in the first place. "Balanced diet," "varied diet," "eat everything," and all the usual clichés and linguistic circumlocutions when you don't know what to say, used as a false first step in "lifestyle modification." If there is no significant initial response to generic guidelines, dietary management should be tailored more specifically at the clinical nutrition level, acting on the underlying pathways that produce a poor response, addressing different pathways: microbiota, oxidative stress, inflammation, nitric oxide, etc.
The focus should be on the integration of individualized dietary modifications by competent individuals in clinical nutritional management and judicious pharmacotherapy, which in some cases also includes consideration of deprescription when appropriate. Hypertension, lipids, etc., are only a reflection of poor metabolic health, and focusing on the numbers is to confuse cause and consequence, health and marker. In fact, high blood pressure is not just "hypertension," but the manifestation of vascular and metabolic dysfunction that goes beyond hypertension. For example, there is evidence showing that insulin resistance and diabetes often develop. Both hypertension and diabetes share mechanisms such as activation of the renin-angiotensin axis, as well as inflammatory, oxidative, and microbiota pathways, etc., which show underlying metabolic damage that needs to be addressed differently than trying to lower various numbers with various drugs.
Reasoning through conceptual categories and numerical positivism produces a reductionist inductive logic that overshadows the clinical reasoning of vascular and metabolic physiology. Medicine that ignores the metabolic basis of chronic diseases simply medicalizes under the illusion of controlling variables, covering up symptoms without addressing the causes.
SODIUM REDUCTION AND THE MYTH OF LOW-SALT DIETS
Despite being widely recommended, the scientific evidence on sodium reduction is surprisingly poor, based mostly on changes in physiological markers rather than on objective reductions in mortality. It is essential to understand this aspect, given that lowering blood pressure does not necessarily reduce absolute mortality. Filippou conducted a systematic review of the level of sodium restriction in the DASH diet, finding a smaller reduction in blood pressure in the analysis of subgroups with greater sodium restrictions. In other words, diets that were less restrictive in sodium (>2.4 g) showed a greater effect on lowering blood pressure than more stringent levels of sodium reduction (Filippou et al 2020). It is possible that excessive restriction may activate compensatory mechanisms such as activation of the renin-angiotensin-aldosterone system, increased sympathetic tone, or alterations in electrolyte homeostasis that counteract the expected hypotensive effect.The answer is provided by comparative clinical trials such as that by Filippou et al, which shows that a Mediterranean diet with sodium restriction achieves a greater reduction in systolic blood pressure than the DASH diet and than sodium restriction alone in adults with grade 1 hypertension or high blood pressure. This shows that there are dietary elements that may be as important as or more important than sodium restriction. The Mediterranean diet with extra virgin olive oil, high in polyphenols and antioxidants that exert vasodilator effects, rich in anti-inflammatories and antioxidants, improves endothelial function and reduces vascular resistance. The intake of certain minerals with food (magnesium, potassium, and calcium) may also have contributed. For example, higher levels of circulating magnesium are inversely related to hypertension (Tirani et al 2025), with a relevant odds ratio (OR = 0.65).
However, the issue is to document reductions in absolute mortality, not to maximize reductions in blood pressure. A Cochrane systematic review evaluated the long-term effects of dietary salt reduction on mortality and cardiovascular events by analyzing eight randomized controlled trials (RCTs) with more than 7,000 people and follow-ups over several years. No solid evidence of a reduction in all-cause mortality was found in normotensive or hypertensive populations, although there is a trend toward a reduction in cardiovascular mortality and cardiovascular events in hypertensive individuals. These reductions in events were mainly driven by one high-weight trial, so the certainty of the evidence is low (Adler et al 2014), showing that there are very few controlled studies, despite this being a widely applied recommendation.
Recent systematic reviews and meta-analyses show that adherence to DASH-type diets reduces all-cause mortality, cardiovascular disease, and cancer (Soltani et al, 2020). However, the question is whether the reduction in mortality is due to sodium reduction or to an overall improvement in diet quality.
People's sensitivity to salt differs markedly, so an individual's blood pressure responds differently to changes in sodium intake. Interestingly, salt sensitivity itself is an independent risk factor for cardiovascular morbidity and mortality in both hypertensive and normotensive populations. Some studies have found that salt sensitivity is a risk factor that increases mortality, independently of blood pressure and even salt intake (Weinberger et al, 2001). In other words, negative vascular responses can occur even in the absence of hypertension and even when adjusting for salt consumption, with Mendelian randomization studies reinforcing this finding.
LOWER BLOOD PRESSURE AND MORTALITY: NOT SO CLEAR IN ALL PEOPLE
A Cochrane review (Graudal et al 2020) shows that the effect of sodium restriction depends on baseline blood pressure levels, so the effect of sodium reduction is only relevant in people with higher blood pressure (>140 mmHg), being practically nil in lower ranges, with additional ethnic and individual differences. This review also evaluated some compensatory effects on different hormones. Sodium reduction caused a significant increase in plasma levels of several hormones such as renin, aldosterone, adrenaline, and noradrenaline, activation of the salt-conserving hormonal system, and stress hormones, which could counteract the hypotensive effect and have implications for long-term cardiovascular health.At the pharmacological level, the picture is mixed. In people under 60 years of age, there is no clear evidence of absolute decreases in mortality with antihypertensive drug treatment (Musini et al 2017). Another Cochrane systematic review of controlled studies has shown no clear evidence of decreases in mortality in people with mild hypertension (Diao et al, 2012). However, reductions in absolute mortality have been found in people over 60 years of age with moderate and severe hypertension (Musini et al 2019), showing a significant reduction in total mortality, cardiovascular mortality, and cerebrovascular mortality. However, the probabilities must be understood. There is an absolute risk reduction of 10 deaths per 1,000 participants (110 per 1,000 vs. 100 per 1,000 in the treatment group) over an average duration of 3.8 years. That is, an approximate reduction in mortality of 1 death per 100 drug treatments during that time. Additionally, the effect of the medication is limited by age. In people aged 80 years or older, a reduction in cardiovascular events was observed, but there was no significant decrease in total mortality (Musini et al, 2019). It is intuitive that, after a certain age, the increased likelihood of adverse effects (falls, orthostatic hypotension, interactions) becomes more significant, counteracting the possible cardiovascular benefits of the medication.
RISKS OF ANTIHYPERTENSIVE MEDICATION AND DEPRESCRIBING
In older people, a high percentage of deaths are due to accidents (up to 20% in some studies), with falls being one of the leading causes of death in this population. A high percentage of falls cause serious injuries, resulting in fractures and problems of loss of functionality due to prolonged immobilization, increased risk of clots, and hospitalization. Reducing blood pressure below a certain threshold, especially in the elderly, can lead to falls, which can cause serious and fatal injuries, and cerebral hypoperfusion, which can lead to cognitive decline and neurological damage. Therefore, priority should be given to functionality, quality of life, risk minimization, and a broader sense of cardiovascular and cerebrovascular risk than simply lowering blood pressure numbers.Nursing home residents are particularly prone to falls due to age-related physiological changes (e.g., blood pooling in the veins, decreased cardiac output, decreased baroreceptor sensitivity), as well as a higher prevalence of osteoporosis, limited mobility, cognitive impairment, polypharmacy, frailty, etc. Orthostatic hypotension, a trigger for falls and fractures, is a common complication of antihypertensive treatment, with the highest risk in the period immediately after treatment initiation. In a large cohort, the fracture incidence rate (per 100 person-years) in the antihypertensive group was 5.4 compared with 2.2 in the control group (adjusted HR 2.42). The number of falls decreased over the months of follow-up but remained high at 90 days. The findings suggest that initiation of antihypertensive medication is associated with an increased risk of fracture in older nursing home residents, emphasizing the need for caution when initiating therapy, especially in the high-risk period after starting the medication (Dave et al 2024).
Another way to look at the impact of antihypertensive medication is through drug withdrawal (deprescribing) studies. The efficacy and safety of deprescribing antihypertensive drugs has been evaluated through a synthesis of recent randomized clinical trials (Crisafulli et al, 2021). Only two studies meeting the inclusion criteria were identified. The first included patients aged 80 years and older with blood pressure <150 mmHg treated with at least two antihypertensive drugs for at least one year, and found no significant differences in blood pressure, quality of life, frailty, or adverse events after a reduction in medication at 12 weeks. The second study included adults aged 40 to 70 years without cardiovascular disease and demonstrated non-inferiority of deprescribing in the 10-year cardiovascular risk SCORE, although with a slight increase in systolic and diastolic blood pressure. Recent Cochrane systematic reviews on deprescribing in older adults show no significant effects on mortality (Gnjidic et al., 2025), although uncertainty is high due to the low number of studies conducted, so interpretation requires caution.
Jing et al., 2024 evaluated the effects of deprescribing antihypertensive medications on cognitive function in more than 12,000 nursing home residents over the age of 65 (Jing et al, 2024). The results showed that the intervention group undergoing deprescribing was associated with a lower probability of cognitive decline. Among patients with dementia, this reduction was even greater, suggesting that there may be a more pronounced benefit in people with compromised neurological health. The study highlights the complex relationship between blood pressure and neurological health in older people, given that hypertension is a risk factor for cognitive decline on the one hand, but also that the use of antihypertensive drugs can have negative effects on the functionality of vascular perfusion in the brain. Therefore, prescribing in older people should be done in a less generalized manner, carefully balancing the individual risk profile.
These findings reinforce the need to periodically reassess the indication for antihypertensive drugs in contexts of polypharmacy, polypathology, and low absolute risk (younger people, lower blood pressure, etc.). Therefore, an assessment of drug use and other ways of managing hypertension beyond simply resorting to medication is key, as reducing the pharmacological burden could prevent the progression to frailty and adverse and fatal clinical events in older people, and move away from comprehensive non-pharmacological approaches in younger people.
PHYSIOLOGICAL AND PHARMACOLOGICAL REDUCTION OF BLOOD PRESSURE
Pharmacological reduction of blood pressure can be more problematic than lowering blood pressure by other means that impact the underlying metabolic mechanisms that produce it. Pharmacological blood pressure reduction is characterized by a "forced" decrease by activating specific physiological mechanisms (renin-angiotensin-aldosterone system, sympathetic tone, renal tubular transport, etc.). Although pharmacological activation is effective, it does not always improve physiological vascular adaptations and intrinsic vascular function. In contrast, non-pharmacological interventions can modulate a set of causal mechanisms directly involved in the genesis of hypertension, producing a decrease not only in blood pressure but also in its physiological causes, favoring a set of adaptive mechanisms that integrate multiple levels of regulation of endothelial function that translate into decreases in blood pressure. Both things seem the same, but they are not. One merely involves the pharmacological activation of a tension mechanism, which does not necessarily promote adaptive circulatory homeostasis or an improvement in baroreflex autoregulation, etc., unlike improving metabolic causes by promoting favorable vascular remodeling, more adaptive arterial distensibility, etc.The fact that the impact of sodium reductions is not so clearly evident in absolute mortality may be due in part to disturbances in cellular ionic, hormonal, and metabolic balance, compromising the electrochemical gradient necessary for the myocardium and other organs, as well as increasing sympathetic stress through compensatory effects that may amplify the proarrhythmic environment to some extent. This elevates renin/angiotensin II/aldosterone and catecholamines, increasing vasoconstriction and afterload, and may elevate heart rate due to increased sympathetic tone. In the longer term, this neurohormonal activation could promote structural remodeling (hypertrophy/fibrosis) and increased myocardial excitability. Aldosterone, on the other hand, increases potassium (and sometimes magnesium) excretion, which may cause prolongation/dispersion of repolarization, in addition to ionic alterations through Na+/Ca2+ exchange and channels involved in the action potential.
Another relevant aspect is the reduced response to sodium restrictions associated with age. Filippou's study shows a cutoff point at 50 years of age. With age, arterial baroreceptor sensitivity decreases and arteries tend to become stiffer, which reduces the hemodynamic response to changes in extracellular volume or sympathetic tone, decreasing functional adaptations and the ability to induce vasodilation in this context. Aging is associated with progressive deterioration in renal function, which alters sodium excretion capacity and sensitivity to its reduction. In addition, this can alter the balance of the renin-angiotensin-aldosterone system (RAAS), activating it more strongly in a compensatory manner, limiting the net effect on blood pressure. Sarcopenia and negative body changes affect extracellular volume, also worsening homeostasis. Medication may have modulated the sodium system, reducing the margin for additional effect from diet. Inflammatory cytokines and reactive oxygen species produced by poor metabolic health and changes in body composition promote endothelial dysfunction, reduce the bioavailability of nitric oxide, and reduce the vasodilator response. Additionally, renal aging involves loss of functional nephrons and tubular atrophy, increasing vulnerability to electrolyte imbalances and inducing neurohormonal activation that may respond to low sodium load as if the body were in hypovolemia or threatened with dehydration, perpetuating proinflammatory and proarrhythmic hormonal signals.
In short, it is clear that simply reducing salt is a simplistic approach that, once again, is based on a reductionist line of reasoning that prioritizes the part over the whole. The response to sodium reduction is compromised with age, and perhaps chronic sodium restriction itself could produce some metabolic and electrolyte alterations that have been little considered, clinging to blood pressure figures. However, the balance between the potentially positive and potentially negative effects we are discussing is undoubtedly complex, so the definitive answer must come from controlled clinical trials that yield results on hard markers in various populations and subgroups. Surprisingly, despite the fact that it critically affects millions of people, these studies have not yet been sufficiently conducted, even though only a controlled empirical evaluation can fully clarify this issue. All in all, the dietary approach for most people should avoid being reduced simply to sodium restriction and should focus primarily on improving the quality of the foods included. Based on an initial response, a more specific clinical nutrition approach covering different aspects can be considered.
COMORBIDITIES AND PRESENCE OF OTHER RISK FACTORS
Antihypertensive treatment is considered in the context of people's health (additional risk factors, etc.). For years, the Cochrane group has lamented the lack of sufficient studies that objectively demonstrate absolute reductions in mortality in the treatment of people with diabetes with antihypertensive drugs, also showing that intensive therapies carry risks that in some cases may outweigh the benefits (Arguedas et al, 2013). In addition, lower blood pressure levels multiply the risk of serious side effects, so that the NNH may exceed the NNT. Furthermore, the decrease in mortality in these studies comes from non-cardiovascular causes, suggesting biases in their design. Other meta-analyses in people with diabetes show unimpressive absolute mortality results, with an RR > 0.9, depending on baseline BP values, BP results achieved, and only from 140 mmHg (Brunström, M., & Carlberg, B, 2016).With an intermediate level of risk in people with different comorbidities, studies on composite outcomes conducted with thousands of people fail to show benefits, except perhaps in cardiovascular events in subgroups with higher blood pressure > 140 mmHg (Lonn et al, 2016). Even in people with comorbidities, there are not many studies that provide absolute mortality data. Those that do (Elgendy et al, 2016) are not well-controlled studies, which causes many problems in their interpretation. On the one hand, people who achieve better blood pressure readings may be more responsible and have made greater lifestyle changes, have a better baseline prognosis, etc., so the pharmacological effect is confounded. Blood pressure itself is also confounded, as it may indicate systemic deterioration, frailty, polypharmacy, etc., rather than good health. Therefore, the effect on mortality of the different blood pressure ranges achieved is also confounded.
Many physicians actually initiate treatments justified by the presence of some criterion considered a risk factor (often questionable), with a "preventive" consideration problematically assumed by poor probabilistic reasoning that fails to see the prior probability and to adequately weigh the probability of non-event in the Bayesian calculation (NPV, P(¬E)).
CONCLUSIONS AND CLINICAL RELEVANCE
I hope I have demonstrated that reducing cardiovascular risk and damage to the vessels in terms of microcirculation and macrocirculation is broader than reducing hypertension numbers by reducing salt or resorting to medication, ignoring everything else. Antihypertensive drugs may have their use, particularly in people whose life situation and clinical reality do not allow for other options. However, there are also millions of people who are prescribed these drugs in a questionable manner, without understanding their probability of benefit, which for many people is nil. Although antihypertensive medication is one of the "star" treatments in medicine, controlled studies show a clear benefit only in a narrow age range with higher blood pressure values. At the individual level, the probability of benefit from drug treatment is much lower than doctors and patients probably think. Any reasoning that seeks to create a justification at the population level must start from the premise that reducing salt and prescribing drugs is not a positive thing if it displaces other aspects that are physiologically more relevant to the overall prognosis. Therefore, the rationalizing nature of mechanistic logic should not compromise clinical knowledge and probabilistic reasoning, which is something else entirely.Many of the current international clinical guidelines raise central problems, guiding the treatment of high blood pressure outside the context of metabolic health and underlying vascular health. At the nutritional level, most guidelines focus on sodium reduction, with poor study of nutritional aspects by all of them. Blood pressure figures are better focused in some guidelines than in others in terms of the target population. Other guidelines, such as those of the AHA and AMA in the US, suggest medicalizing virtually the entire living population, to no one's surprise.
https://targetbp.org/
Drug treatment in low-risk groups not only appears to be an ineffective intervention, but may even increase mortality, according to some studies. Cochrane meta-analyses themselves highlight the absence of consistent reductions in absolute mortality, which calls into question the strategy of preventively medicating the majority of the population, except for those clearly justified by a high risk profile.
The European ESC guidelines make some mention of the conflicting evidence on salt. That's something, at least. However, they practically avoid talking about nutrition.
https://www.escardio.org/Guidelines/Clinical-Practice-Guidelines/El...
NICE also fails.
https://www.nice.org.uk/guidance/ng136/resources/hypertension-in-ad...
In short, the guidelines present a biased view of hypertension, with a biochemical theoretical basis that selects only those factors that lead to its medicalization, something that can hardly be considered an innocent oversight. This is even more so given that the evidence continues to raise considerable doubts. The nutritional approach demedicalizes people, and is therefore a threat to a system that moves a lot of money. The number to be treated at the individual level is high, so the patient must understand that cardiovascular risk still exists even if a drug lowers blood pressure (or lipid levels, etc.). We therefore criticize the reductionism of a medicalized approach to hypertension, when there are multiple mechanisms involved in the regulation of blood pressure and vascular function: autonomic balance, endothelial function, arterial stiffness, low-grade systemic inflammation, gut microbiota, and insulin resistance, among many others.
If you want to moderate your salt intake, reducing ultra-processed foods is a good start. But just as important, if not more so, than reducing numbers is staying active, eating a diet high in a variety of vegetables and fruits (not just the usual ones, but also berries, etc.), consuming virgin olive oil daily, etc. The mortality benefit observed with the DASH pattern may derive more from the overall improvement in the inflammatory, antioxidant, and vasomodulatory profile of the diet than from a linear reduction in sodium. There is nothing special about the "DASH diet" or "Mediterranean diet" except for the foods they contain, particularly vegetables, etc. What should be clear is that in most cases, the main issue is not blood pressure numbers, but metabolic health. Moreover, the former is primarily a consequence of the latter. It is not enough to say "eat better" when the doctor himself does not understand what that means in the first place. "Balanced diet," "varied diet," "eat everything," and all the usual clichés and linguistic circumlocutions when you don't know what to say, used as a false first step in "lifestyle modification." If there is no significant initial response to generic guidelines, dietary management should be tailored more specifically at the clinical nutrition level, acting on the underlying pathways that produce a poor response, addressing different pathways: microbiota, oxidative stress, inflammation, nitric oxide, etc.
The focus should be on the integration of individualized dietary modifications by competent individuals in clinical nutritional management and judicious pharmacotherapy, which in some cases also includes consideration of deprescription when appropriate. Hypertension, lipids, etc., are only a reflection of poor metabolic health, and focusing on the numbers is to confuse cause and consequence, health and marker. In fact, high blood pressure is not just "hypertension," but the manifestation of vascular and metabolic dysfunction that goes beyond hypertension. For example, there is evidence showing that insulin resistance and diabetes often develop. Both hypertension and diabetes share mechanisms such as activation of the renin-angiotensin axis, as well as inflammatory, oxidative, and microbiota pathways, etc., which show underlying metabolic damage that needs to be addressed differently than trying to lower various numbers with various drugs.
Reasoning through conceptual categories and numerical positivism produces a reductionist inductive logic that overshadows the clinical reasoning of vascular and metabolic physiology. Medicine that ignores the metabolic basis of chronic diseases simply medicalizes under the illusion of controlling variables, covering up symptoms without addressing the causes.
#salt #antihypertensivedrugs #DASHdiet #highbloodpressure #cardiovasculardisease #hypertension
References:
Adler AJ, Taylor F, Martin N, Gottlieb S, Taylor RS, Ebrahim S. Reduced dietary salt for the prevention of cardiovascular disease. Cochrane Database of Systematic Reviews 2014, Issue 12. Art. No.: CD009217. https://doi.org/10.1002/14651858.CD009217.pub3
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