Does excessive salt consumption lead to cardiovascular disease indirectly through elevating blood pressure or are there also direct mechanisms?

Excessive Salt Causes Cardiovascular Disease Through Both Blood Pressure-Dependent AND Direct Mechanisms

Excessive salt consumption damages the cardiovascular system through multiple direct pathways beyond its effect on blood pressure, including cardiac hypertrophy, vascular fibrosis, renal injury, immune activation, and metabolic dysfunction. 1, 2, 3

Direct Cardiovascular Damage Independent of Blood Pressure

Salt causes cardiovascular injury through several blood pressure-independent mechanisms that are increasingly recognized as clinically significant:

Cardiac Effects

• Chronic intracellular sodium elevation in the heart leads to mitochondrial dysfunction and direct cardiac injury. 1
• Excessive sodium intake promotes left and right ventricular hypertrophy and fibrosis, perivascular fibrosis of the coronary arteries, and diastolic dysfunction—even in young healthy adults with clinically normal blood pressure. 2
• Those who consume more sodium are more likely to have increased left ventricular mass, which is especially prominent when blood pressure is elevated, suggesting that excess dietary sodium sensitizes the heart to hypertrophic and fibrotic stimuli. 2

Vascular Toxicity

• Sodium appears to be a direct vascular toxin—in experimental models, sodium augments the production and release of vascular injury mediators such as TGF-beta. 1
• Sodium is necessary for aldosterone to inflict fibrosis and scarring in target organs. 1
• High salt intake has unfavorable effects on arterial stiffness, cardiac output, and alterations in sympathetic outflow through mechanisms including excess inflammation and oxidative stress. 1

Renal Damage

• High sodium intake results in massive albumin excretion, oxidative stress, severe renal arteriolar damage, interstitial fibrosis, increased glomerular hydrostatic pressure, glomerular hyalinization, fibrosis, and end-stage renal disease independently of increased blood pressure. 2
• Acute high-salt exposure causes morphological signs of renal injury within 3 days in salt-sensitive rats, mediated by increased leucocyte adhesion without any change in blood pressure. 1
• Sodium can reversibly disrupt normal autoregulation of GFR, a mechanism that potentially exposes the glomerulus to inappropriately high systemic BP, predisposing to hemodynamic injury. 1

Immune System Activation

• Salt activates myeloid and T cells to adopt a pro-inflammatory state, with dysregulation of the gut microbiome, skin resident monocyte/macrophages, regulatory T cells, natural killer T cells, and myeloid-derived suppressor cells contributing to blood pressure. 1
• High salt treatment in both mice and humans reduced Lactobacillus species and increased blood pressure, demonstrating microbiome-mediated effects. 1

Blood Pressure-Mediated Cardiovascular Risk

While direct mechanisms are important, blood pressure elevation remains a major pathway:

• High dietary salt intake is a key driver in elevating blood pressure, with population data suggesting lifestyle factors account for at least up to 5 mm Hg higher blood pressure. 1
• A large RCT in rural China confirmed that reduced dietary sodium and high potassium intake results in lower blood pressure and an associated reduction in major cardiovascular events and mortality. 1
• Meta-analysis of clinical trials identified a statistically significant 20% reduction in cardiovascular disease and stroke events with sodium reduction. 2
• Each 1 g/day sodium increase raises systolic blood pressure by 0.60 mmHg and CVD and stroke risks by 4% and 6%, respectively. 4

Medication Interference

• Excessive dietary sodium intake contributes to resistant hypertension both through directly increasing blood pressure and by blunting the blood pressure-lowering effect of most classes of antihypertensive agents. 1
• Excess sodium intake attenuates the beneficial effects of many antihypertensive drugs, including blockers of the renin-angiotensin-aldosterone system, whereas reducing sodium intake enhances these effects. 2

Clinical Magnitude and Recommendations

• Average sodium intake in US adults is 4,127 mg/day in men and 3,002 mg/day in women, significantly exceeding guideline recommendations. 2
• The American Heart Association recommends limiting sodium intake to <1,500 mg/day, with strong scientific support from experimental, observational, and clinical trial data. 2
• Currently, an average intake below 5 g of salt per day (equivalent to 2.3 g sodium) is recommended to healthy adult people, but this quantity is largely exceeded in most populations. 1
• Excessive salt intake is estimated to cause approximately 5 million deaths per year globally. 3, 5

Common Pitfalls

• Assuming salt only causes cardiovascular disease through blood pressure elevation misses the substantial direct toxic effects on the heart, vessels, kidneys, and immune system. 2, 3
• Failing to recognize that cardiovascular damage from salt can occur even in normotensive individuals with "clinically normal" blood pressure. 2
• Not appreciating that salt sensitivity varies substantially—approximately 50-60% of hypertensives are salt sensitive, with higher prevalence in women, elderly, African Americans, and those with chronic kidney disease. 1, 6, 5
• Overlooking that in Western countries, around 80% of salt ingested is hidden in processed and canned foods, making individual dietary control difficult without population-level interventions. 1