Atherosclerosis develops when plaque (a sticky substance) builds inside the arteries. It happens when cholesterol, fat, blood cells, and other substances form plaque. Plaque causes the narrowing of arteries. As a result, it reduces the oxygen supply to vital body organs. Coronary (artery-supplying) atherosclerosis plays an essential role in cardiovascular disease (CVD). Increased dietary salt intake has deleterious effects on the heart and brain blood vessels.
Previous studies confirmed that long‐term high dietary salt intake leads to hypertension (increased blood pressure; BP) and the progression of CVD (including atherosclerosis) and cerebrovascular (brain) diseases. However, recent research suggests that a high salt intake is a risk factor for atherosclerosis without hypertension.
What Is the Role of Dietary Salt in Normal Body Functioning and Disease?
Dietary salt (sodium chloride) is important to maintain water and sodium homeostasis (a stable system). It also plays a crucial role in BP regulation. Human studies and experiments in animal models provide strong evidence that high sodium intake leads to increased BP. High BP is a well-known risk factor for atherosclerosis.
However, changes in dietary sodium have had varied results in atherosclerosis studies in mouse models. Still, it is difficult to prove these findings in humans. Some studies report that high dietary sodium levels promote atherosclerosis. On the other hand, other studies suggest that low dietary sodium increases atherosclerosis in mice. Hence, the different findings infer a more complex role of salt intake in causing atherosclerosis than a causal relationship mediated through hypertension.
What Are the Effects of Salt Intake on Various Health Parameters Contributing to Atherosclerosis?
Effects of Salt Intake on Blood Pressure: High sodium intake is detrimental to BP (an endpoint for CVD). Evidence supports that higher sodium intake is associated with elevated BP (consistent in animal and human studies). On the other hand, sodium restriction is associated with reduced blood pressure. Decreased sodium intake reduces inflammation (a marker for atherosclerosis).
Effects of Salt Intake on Lipids: Studies suggest salt restriction adversely affects blood lipid levels. The risk of cardiovascular disease (atherosclerosis) increases in proportion to blood lipid levels. Studies demonstrate that total cholesterol and low-density lipoprotein (LDL; also called bad cholesterol) increase with short-term low sodium intake (one week) in non-obese normotensive (normal BP) individuals aged 19 to 78. On the contrary, other studies report that total cholesterol and LDL cholesterol increase during short-term sodium restriction. Hence, it suggests a controversial role of salt intake on cholesterol levels.
Effects of Salt Intake on Vascular Endothelial Function: Vascular endothelial (inner cell layer of a blood vessel) dysfunction (a type of coronary artery disease) can contribute to atherosclerosis. Endothelial dysfunction is associated with high sodium intake in animals and humans. Furthermore, endothelial dysfunction is predictive of future cardiovascular events such as atherosclerosis. Various studies suggest that it is related to the increased oxidant levels caused by high sodium intake through the generation of reactive oxygen species (ROS; ROS form free radicals that contribute to atherosclerosis) in the endothelium. Studies suggest that ROS contribute to the reduced bioavailability of nitric oxide (NO). It is because the half-life of NO decreases in the presence of superoxide anions (a type of ROS). NO plays an important role in vascular function by promoting vasodilation (blood vessel dilation) and inhibiting platelet and leukocyte activation (the important events in atherosclerosis). Hence, reduced NO bioavailability can impair endothelial function during high sodium intake and contribute to the pathogenesis of atherosclerosis.
Effects of Salt Intake on Immunity: Sodium intake can negatively affect the immune system. Atherosclerosis is a component of CVD pathogenesis and consists of chronic (long-term) low-grade inflammation and atherogenesis (plaque formation). Oxidized LDL involved in atherogenesis is involved in mediating T-cell (a type of immune cell) infiltration into atherosclerotic plaques. Hence, a high sodium intake might be associated with an imbalance in immune homeostasis. Further, it has a predisposition toward a pro-inflammatory state.
Effects of Sodium Intake on the Sympathetic Nervous System (SNS): SNS component of the nervous system increases heart rate (HR), BP, and breathing rate. Sodium intake has differential effects on the SNS. As a result, it may adversely affect the cardiovascular system. It can lead to left ventricular hypertrophy (an increase in the size of the left ventricle), vascular remodeling, arterial stiffness, and atherosclerosis.
Effects of Sodium Intake on Diabetic Patients: Diabetes mellitus (DM) and atherosclerosis connect through several pathways. The accelerated development of atherosclerosis has been shown in studies on diabetic patients. It is due to:
Dyslipidemia (Altered Blood Lipid Levels): Diabetes-associated dyslipidemia has received attention in recent years. Dyslipidemia in DM is linked to elevated liver production of LDL and very low-density lipoproteins (VLDL; VLDL is a subfraction of LDL in humans).
Hyperglycemia (Increased Blood Glucose): One of the possible mechanisms is the formation of advanced glycation end-products (AGE), which occurs in a hyperglycemic state. AGEs are not metabolized and accumulate in patients with long-term inadequate blood glucose control. Hence, it may accelerate atherosclerosis in diabetic patients. Excessive glycation (the attachment of glucose to a protein or a lipid molecule) may also play a role in atherosclerosis development. The glycation of red blood cells (RBCs) in type 2 DM patients may impair endothelial function. This process contributes to unstable plaque development with subsequent thrombosis (clot formation) in patients with type 2 DM and atherosclerosis.
Oxidative Stress: DM is associated with increased ROS production and reduced antioxidant activity. Studies demonstrate that increased ROS production is linked to hyperglycemia. Vascular ROS increases are closely related to atherosclerosis in the diabetic context. Hence, antioxidant therapies are considered for the management of both DM and atherosclerosis.
Chronic Inflammation: Chronic inflammation is common in atherosclerosis and DM. Atherosclerosis is a chronic inflammatory condition. In patients with type 2 DM, increased activity of inflammasomes (protein complexes involved in inflammation) is demonstrated along with increased levels of pro-inflammatory cytokines (inflammatory mediators).
The pathogenesis of atherosclerosis and high salt intake are linked. But the mechanisms and molecular interactions are still under discussion. High salt intake has many effects on cardiovascular health, highlighting the association between sodium intake and cardiovascular outcomes. Hence, the dietary sodium guidelines have been challenged because of the emerging evidence suggesting a beneficial role of dietary salt in high-risk groups. It indicates that the current guidelines are strict. Therefore, they may need further revision.