Can iron deficiency cause high blood pressure

A new discovery on how iron deficiency affects the vasculature of the lung could hold the key to improving treatment of pulmonary arterial hypertension.

A new paper from the Lakhal-Littleton Group at Oxford’s Department of Physiology Anatomy & Genetics describes the way in which iron deficiency affects human vasculature - in particular the vasculature of the lung.

Iron deficiency is the most common nutritional disorder in the word. Its prevalence is particularly high in patients with cardiovascular diseases, in whom it is associated with poor outcome.

It has been known for some time that iron deficiency predisposes to pulmonary arterial hypertension (PAH). In this condition, the vasculature in the lungs is constricted and remodelled, and this puts pressure on the right side of the heart. For some time it was thought that PAH is caused by anaemia, a condition in which iron deficiency is the underlying mechanism. Consequently, the only consideration given to iron deficiency in the clinical setting has been in the context of correcting anaemia.

However, previous work from this laboratory has shown that iron deficiency within tissues, such as the heart, is sufficient to cause disease even in the absence of anaemia. In the paper, 'An essential cell-autonomous role for hepcidin in cardiac iron homeostasis', Professor Lakhal-Littleton and her team revealed the first study describing the mechanism linking iron deficiency with heart disease.

This new study explores the links between iron deficiency and PAH. It has found that iron deficiency within the smooth muscle cells of the pulmonary arteries is in itself sufficient to cause PAH, even in the absence of anaemia. The effect of iron deficiency is due to increased release of the vasoconstrictor endothelin-1 from cells of the pulmonary arteries.

Professor Lakhal-Littleton and her team were able to reverse and prevent PAH in mice by both iron supplementation and inhibition of endothelin-1 signalling. Consequently, this study provides a mechanistic underpinning for the observation that iron deficiency raises hypoxic pulmonary arterial pressure in healthy individuals and worsens existing PAH in patients.

Ultimately, this paper demonstrates that it is not anaemia, but rather the lack of iron in the cells of the vasculature that is causing the remodelling of the vessels in the lung present in individuals suffering from PAH. Therefore, it strengthens the rationale for correction of tissue iron deficiency independently of the presence or absence of anaemia.

Associate Professor Samira Lakhal-Littleton, said: ‘This research holds potential to alter the way in which patients with pulmonary arterial hypertension are treated.

‘This provides the rationale for giving iron to patients even when they aren't anaemic, because the target is no longer anaemia, but iron deficiency within tissues.’

The full paper, ‘Intracellular iron deficiency in pulmonary arterial smooth muscle cells causes pulmonary arterial hypertension in mice,’ can be read in PNAS.

Iron deficiency occurs when the body’s iron stores are too low. This interferes with the body’s ability to produce hemoglobin, a component of red blood cells that enables them to transport oxygen.

Iron deficiency causes include blood loss, a lack of iron in your diet, or certain medical conditions. Severe, untreated, or prolonged iron deficiency changes red blood cell (RBC) quantity, size, and function, a condition known as iron deficiency anemia.

Iron deficiency causes tiredness, weakness, poor concentration, and dry skin and nails. Anemia can also cause heart palpitations, shortness of breath, and an increased risk for infections.

This article discusses iron deficiency. It also explores the causes and symptoms of iron deficiency and iron deficiency anemia while suggesting ways you can prevent this condition.

Low Iron and Your Body

Iron is an important nutrient. It helps your body produce hemoglobin and myoglobin, two proteins that carry oxygen in your blood. When you don't get enough iron, this important function is hampered. Your cells don't get what they need to give you energy.

It takes a while to develop symptoms of iron deficiency anemia. When you don't get enough iron in your diet, your body can use stored and recycled iron to form new blood cells. When the iron supply begins to run out, symptoms will develop as your body slows the production of red blood cells.

Stages of Iron Deficiency

Iron deficiency occurs in three stages.

Stage 1: the body’s iron stores begin to be depleted. Your hemoglobin levels may still be normal, but serum ferritin levels are low. Ferritin is a protein that stores iron. You may feel run down and tired, although many people do not have any symptoms.

Stage 2: The body does not have enough iron to build new red blood cells. Instead, the body uses zinc. Blood work may still show normal hemoglobin levels, but transferrin saturation levels (a measure of how much iron is being held in the body) are low, and zinc protoporphyrin (ZPP), which helps use zinc In RBCs, is high. You may feel fatigued and dizzy at this stage, although you may not have any symptoms.

Stage 3: This stage is defined as iron deficiency anemia. In this stage, hemoglobin levels drop below the normal range:

• 12 to 15 g/dL for women
• 14 to 16.5 g/dL for men

At this stage, you will likely feel tired, weak, and short of breath when climbing stairs or exercising. You may also experience headaches, dizziness, and heart palpitations.

Iron Deficiency Causes

Low iron levels can be caused by a few different things, including:

Diet and Absorption

You can develop iron deficiency if you don't eat enough iron-containing foods or if you have trouble absorbing iron. Vegetarians and vegans may be more prone to iron deficiency, especially premenopausal females. This is because non-heme iron, the form found in plants, is not absorbed as well as heme iron, the form found in meat, poultry, and fish.

Some illnesses prevent the absorption of iron, including:

• Irritable bowel syndrome
• Celiac disease

Weight loss surgeries may also lead to iron deficiency. Gastric bypass, for example, often involves the removal of sections of the stomach or intestine. This can interfere with iron absorption.

Phytic acid is an antioxidant found in legumes, rice, and grains. It can inhibit iron absorption, which may contribute to iron deficiency anemia.

Extra Iron Requirements

During pregnancy, you have greater blood volume. A developing fetus also needs oxygen-rich RBCs for energy. This is why you need more iron during pregnancy. If you're pregnant and not taking prenatal vitamins, you may fall short of this goal.

Actively growing bodies need extra iron to provide energy to developing cells. That's why it's also important for babies, children, and teens to get plenty of iron. Female athletes may also need additional iron.

Blood Loss

Normal or heavy menstrual bleeding can lead to iron deficiency anemia. For this reason, females generally need more iron than males.

Medical conditions that cause chronic bleeding, especially when it's rapid, can lead to low blood volume and iron deficiency anemia.

These conditions include:

• Ulcers
• Hemorrhoids
• Polyps
• Colon cancer

In these cases, symptoms tend to be more severe.

Surgery, childbirth, or an injury can also cause excessive blood loss. After donating blood, you may also be a little low in RBCs for a few days. However, in healthy people who donate blood, RBC volume is usually corrected without noticeable symptoms.

Conditions Associated with Iron Deficiency

Some situations are associated with iron deficiency but don't cause it.

For example:

• Being underweight. Calories from any source do not affect iron absorption. Still, people who are underweight are often iron deficient because there isn't enough iron in their diet.
• Kidney disease. Erythropoietin is a hormone produced by the kidneys. It plays an important role in stimulating red blood cell production. You may need erythropoietin replacement to stimulate red blood cell production if you have kidney disease. Dialysis does not correct this hormone problem.
• Some cancers, especially those that involve white blood cells, are associated with low RBC levels. Leukemia and lymphoma, for example, can impair the production of RBCs. Most cancer treatments also suppress the production of RBCs. The lack of RBCs doesn't decrease iron levels, but it prevents the iron in the body from doing what it is meant to do.

Iron Deficiency Symptoms

If you have iron deficiency anemia, it can lead to a number of symptoms. They may progress quickly, or they may appear over the course of weeks or months.

• Fatigue
• Weakness
• Problems with memory and thinking
• Feeling cold
• Headaches or dizziness
• Dry, brittle hair, skin, and nails
• Strange cravings for metal, dirt, paper, or starchy food, called pica
• Red, inflamed tongue, called glossitis
• Frequent infections
• Heart palpitations
• Shortness of breath
• Restless legs syndrome

Symptoms can come on quickly with severe iron deficiency or rapid blood loss. Symptoms of moderate iron deficiency may be slower to appear.

Complications

Extreme iron deficiency anemia can cause tachycardia or rapid heart rate. It can also cause low blood pressure. In children, extreme iron deficiency may contribute to learning and concentration problems.

Pregnant women who have an iron deficiency can have low energy. They also have an increased risk of low birth weight babies and premature birth.

Diagnosing Iron Deficiency

A complete blood count (CBC) is a blood test that counts your platelets and your red and white blood cells. This test can only suggest iron deficiency anemia, because there are also other causes of anemia. Your doctor will try to identify the cause based on your medical history and exam.

Your doctor may order tests to see if you have gastrointestinal (GI) bleeding. If your doctor doesn't suspect GI blood loss, you may need to start a trial of iron supplements with close follow-up. If there is no improvement after a few weeks or if your doctor is still unsure about what's causing your anemia, you may need iron studies.

These blood tests usually measure:

• Serum ferritin
• Serum iron
• Serum transferrin
• Transferrin

If the results are uncertain, your doctor may order other blood tests. If the cause still can't be found, bone marrow biopsy is the gold standard for diagnosis. During this procedure, a sample of bone marrow is taken using a hollow needle. 

Physical Examination

For many conditions, a physical exam is the most important diagnostic tool. Symptoms of iron deficiency, though, don't usually develop until weeks or months after you have an abnormal blood test.

These late symptoms include:

• Pale skin
• Rapid heartbeat
• Low blood pressure while standing

This is why a physical exam usually can't identify an iron deficiency.

Follow-Up Testing

It's very important to find the cause of iron deficiency anemia. One of the first things many doctors do is look for occult blood loss. This is hidden or unnoticed blood loss. The most common cause is bleeding from the colon.

The first step toward identifying this cause is to look for blood in a stool sample. If there is no blood, your doctor may still order a colonoscopy or endoscopy, especially if there is no other obvious cause. During this test, a healthcare provider looks at the inside of your GI system with a camera attached to a long, flexible tube.

Colonic polyps, bleeding ulcers, and even gastrointestinal cancer can be causes of iron deficiency. Some other conditions that your doctor might consider include:

• Helicobacter pylori, a bacteria that can cause ulcers
• Celiac disease
• Autoimmune gastritis

Treating Iron Deficiency

Treatment of iron deficiency is based on two important approaches:

• Correcting the underlying problem
• Replacing iron levels
  

Replacing Iron Levels

Iron levels can be corrected by increasing iron in the diet or taking iron supplement pills. If these options don't help, you may receive an iron injection. The latter may be needed if your iron deficiency is related to an intestinal problem. If your body can't absorb iron, taking a pill or eating food rich in iron won't correct the problem.

Medical or Surgical Intervention

Some causes may require other types of intervention. For example, a bleeding polyp in your colon may need to be removed. A biopsy can make sure it isn't cancer.

For some people, stomach bleeding may be related to the use of blood thinners. When this happens, you may need a lower dose or a different blood thinner. If you have had a major episode of blood loss due to something like surgery or trauma, you may need a blood transfusion.

Preventing Iron Deficiency

Healthy people can usually prevent iron deficiency with diet. Healthy intake differs for different people:

• Healthy adult males: 8 mg per day
• Healthy premenopausal adult females: 18 mg per day
• Healthy pregnant females: 27 mg per day
• Healthy postmenopausal females: 8 mg per day

After menopause, healthy women need less iron because they do not experience blood loss due to menstruation.

Good dietary sources of iron include:

• Meat
• Poultry
• Legumes
• Oysters
• Tuna
• Pork
• Nuts
• Dark green vegetables
• Tomato juice
• Potatoes

You can help your body absorb non-heme iron by combining vegan sources of iron with a food rich in vitamin C. For example, drink a glass of orange juice with a plate of spinach, or add green peppers to beans.

You may need higher amounts if you have a condition that interferes with your iron levels. You may need iron injections if you can't get enough through your diet or with an oral supplement.

Dietary Supplements

Most males and postmenopausal females get enough iron from food and should not take iron supplements unless prescribed by a doctor. Pregnant females should take prenatal vitamins, which usually contain iron. Females who have heavy periods may also need to take iron supplements. If you need to take an iron supplement, don't take more than 45 mg per day unless your doctor tells you to.

Even at recommended doses, iron supplements can cause uncomfortable constipation. They can also cause more serious side effects, such as iron toxicity. Iron supplements are especially dangerous for people who have hemochromatosis. This condition is characterized by iron overload.

Adult iron supplements can be toxic for young children. Be sure to keep them in tightly capped, childproof bottles.

Summary

Iron deficiency can lead to iron deficiency anemia. When you have this condition, you may have symptoms like weakness, dry skin and nails, and poor concentration. In severe cases, you may have heart palpitations and shortness of breath.

Iron deficiency can be caused by a poor diet. It can have other causes, too, like GI bleeding or problems with iron absorption.

Iron deficiency can be diagnosed with blood tests, endoscopy, or a bone marrow biopsy. Treatment involves correcting the underlying cause and replacing lost iron. In healthy people, the condition can usually be prevented by making sure to get plenty of dietary iron.

Frequently Asked Questions

• How do you know if you have low iron?

  If you have symptoms of iron deficiency anemia, you may have low iron levels. This is often how low iron initially presents itself. Symptoms include:

  • Fatigue
  • Weakness
  • Poor or worsened concentration
  • Feeling cold
  • Headaches
  • Dizziness
  • Pica, or eating non-food items like metal, paper, or dirt
  • Glossitis, a red and inflamed tongue
  • Heart palpitations
  • Frequent infection
  • Shortness of breath
  • Restless leg syndrome
  • Dry or brittle hair, skin, and nails

• What causes low ferritin levels?

  Low ferritin levels are a sign of iron deficiency. It can be caused by any condition that affects iron levels.

  Ferritin is a protein that contains iron. When a person shows high or low iron levels symptoms, a doctor may order a ferritin blood test to help diagnose.

• How do you treat iron deficiency?

  Iron deficiency is treated by resolving the underlying cause and then correcting iron levels. Oral iron supplements and nutritional counseling can help correct a person's iron levels. However, if oral iron does not work, nutrition may need to be administered intravenously.

• Can iron deficiency cause weight gain?

  Yes. It is unclear exactly how iron deficiency leads to weight gain. Some suspect it is due to fatigue, which causes you to be less active. Others suspect iron deficiency may slow your metabolism. Either way, research shows treating iron deficiency anemia helps to promote weight loss.

  Does iron deficiency affect blood pressure?

  Lack of iron regulating protein contributes to high blood pressure of the lungs.

  Can anemia cause high blood pressure?

  Anemia is associated with higher cardiovascular risk, higher blood pressure values, and lower dipping status in hypertensive patients, and hemoglobin should be monitored in hypertensive patients.

  Is iron associated with high blood pressure?

  Patients with hypertension with iron overload display a potentiation of the sympathetic activation characterizing high blood pressure which appears to be related to iron load and to the metabolic alterations frequently accompanying this condition.

  Can anemia cause high systolic blood pressure?

  Isolated systolic hypertension is when your systolic blood pressure is high, but your diastolic blood pressure is normal. It can occur naturally with age or can be caused by specific health conditions, including anemia, diabetes, and hyperthyroidism.