Vitamin D Deficiency and Cardiovascular Risk: we’re still in the Dark

For decades, observational studies has provided evidence of the association between reduced levels of 25-hydroxy vitamin D and increased risk of cardiovascular disease. It is generally accepted that vitamin D deficiency is in some way related to adverse cardiovascular outcomes. It has been postulated that this association may be a result of reverse causality in which unhealthy and less mobile individuals are less likely to be exposed to sunlight, or perhaps due to a physiological chain of events in which low vitamin D concentrations promote downstream vascular remodeling and hemodynamic instability.

And yet, after thousands of studies have been published on the topic, the global medical community remains very much in the dark regarding whether a true relationship exists between vitamin D deficiency and increased cardiovascular risk. A small number of clinical trials which have aimed to assess the possibility of a direct, causal relationship between low vitamin D concentrations and poor cardiovascularoutcomes in select patient populations do exist. Unfortunately, metaanalyses of these trials demonstrate widespread inconsistency in trial duration, sample size, type of vitamin D intervention and route of administration, and primary outcomes. 

One large patient population may be able to shine a much-needed spotlight on this topic. Individuals with chronic kidney disease (CKD), specifically those with end-stage kidney disease requiring dialysis, experience dramatically increased risk of cardiovascular disease compared to that of the general population. In addition, the progressive loss of kidney function also results in disruption of regular vitamin D metabolism, thus the prevalence of severe vitamin D deficiency in this patient population is extremely high. 

In general, approximately 25% of all deaths in CKD are attributed to Sudden Cardiac Arrhythmic death (SCD), which results primarily from miscommunication between the sympathetic and parasympathetic branches of the cardiac Autonomic Nervous System (ANS) and the atrio-ventricular and sino-atrial nodes of the heart. Changes in sinus rhythm controlled by the electrical signals passed from the ANS to the heart can be quantified by measuring Heart Rate Variability (HRV) with a typical ambulatory heart monitor.