Does vitamin D deficiency play a role in the pathogenesis of chronic heart failure? Do supplements improve survival?

LOW VITAMIN D CONTRIBUTES TO THE PATHOGENESIS OF HEART FAILURE

In recent years, ideas about the pathophysiology of heart failure have expanded from a purely hemodynamic view to a more complex concept involving inflammatory cytokines and neurohormonal overactivation.⁸

Animal studies first showed vitamin D to inhibit the renin-angiotensin-aldosterone system, activation of which contributes to the salt and water retention seen in heart failure.^4,9

In addition, vitamin D has a number of effects that should help prevent hypertension, an important risk factor for heart failure. It protects the kidney by suppressing the reninangiotensin-aldosterone system, prevents secondary hyperparathyroidism and its effects on vascular stiffness, prevents insulin resistance, and suppresses inflammation, which protects vascular endothelial cells.¹⁰

The first studies to show a connection between cardiovascular homeostasis and vitamin D status were in animal models more than 20 years ago. These studies showed that 1,25-dihydroxyvitamin D₃ acts directly on cardiomyocyte vitamin D receptors, which are widely distributed throughout the body in several tissue types.¹¹

Excess PTH levels associated with low vitamin D levels may play a role in cardiovascular disease by leading to cardiomyocyte hypertrophy and interstitial fibrosis of the heart.¹² Animal studies have found that vitamin D suppresses cardiac hypertrophy.¹³ Vitamin D also plays a role in cardiomyocyte relaxation and may abrogate the hypercontractility associated with diastolic heart failure.^2,14

Currently, it is unclear whether vitamin D deficiency is a causative risk factor for heart failure or simply a reflection of the poor functional status of patients with heart failure that leads to decreased exposure to sunlight. This debate will continue until further randomized clinical trials address this association.

VITAMIN D AND HEART TRANSPLANTATION

One would expect that patients with endstage organ failure would be at high risk of vitamin D deficiency because of limited sunlight exposure. However, few studies have evaluated the role of this vitamin in heart transplant recipients.

Stein and colleagues¹⁵ measured serum 25-hydroxyvitamin D₃ immediately after transplantation in 46 heart and 23 liver transplant recipients. Levels were low in both types of transplant recipients, but liver transplant recipients had significantly lower levels than heart transplant patients. This could be explained by malabsorption and impaired synthesis of 25-hydroxyvitamin D₃ in end-stage liver disease.

Also, an important point is that osteoporosis is prevalent in postcardiac transplant patients and likely related to the immunosuppressive agents these patients must take.¹⁶ In theory, increasing the body’s stores of vitamin D during the pretransplant period could lower the rate of bone loss and osteoporosis after cardiac transplantation.

Further investigation is needed to determine whether restoring adequate levels of vitamin D at the time of or after transplantation prevents graft rejection or improves survival.

VITAMIN D SUPPLEMENTATION AND SURVIVAL IN HEART FAILURE

The best laboratory test to assess vitamin D levels is the serum 25-hydroxyvitamin D₃ concentration. A level between 20 and 30 ng/mL (50–75 nmol/L) is considered insufficient, and a level below 20 ng/mL (50 nmol/L) represents vitamin D deficiency.^4,5,11

Vitamin D insufficiency is typically treated with 800 to 1,000 IU of vitamin D₃ daily, whereas deficiency requires 50,000 IU of vitamin D₃ weekly for 6 to 8 weeks, followed by 800 to 1,000 IU daily.¹⁹ The goal of therapy is to increase the serum 25-hydroxyvitamin D₃ level above 30 ng/mL.¹⁹

Currently, it is unknown if vitamin D supplementation improves survival in heart failure. We recommend testing for vitamin D deficiency in all patients with heart failure and treating them as described above. For heart failure patients that are not deficient, daily intake of 800 to 1,000 IU of vitamin D is reasonable. Our review underscores the need for more studies to evaluate the efficacy of vitamin D replacement in improving survival in patients with heart failure.

KEY POINTS

• Screening for vitamin D deficiency in patients with heart failure is appropriate and encouraged.
• Vitamin D deficiency is common in patients with heart failure and in heart transplant recipients.
• In theory, achieving adequate levels of vitamin D would have a beneficial effect on patients with heart failure.
• Randomized controlled trials are needed to determine if vitamin D supplementation confers a survival benefit in patients with heart failure who have deficient vitamin D levels.