Discussion
In 2014, 8.0% of all Medicare Fee-For-Service beneficiaries had a
diagnosis of AF (28). In the 65 and older population, AF prevalence was
higher among males (10.5%) than females (8.4%) and was highest among
Non- Hispanic Whites (10.2%), followed by American Indians/Alaska
Natives (5.9%), Hispanics (5.0%), Blacks/African Americans (5.1%),
and Asian Pacific Islanders (4.9%). The cause of these differences in
prevalence is unknown but recent study suggests that there may be some
genetic protection against AF in minority populations (29).
Several additional reports have evaluated the prevalence of AF in CKD
patients but few have studied if CKD in AF patients independently
increases MACE when adjusted for previously defined traditional risk
factors for MACE. Our study is one of the first to assess the effects of
CKD on MACE in an African American and Latino NVAF population and
provides evidence that a decreased GFR was an independent risk factor
for MI, Death and MI, stroke and death among these patients. Our data
reinforces other studies that have identified renal dysfunction as an
added predictor of MACE, although our data is unique in that it is
predominantly from a non-Caucasian population.
Different than other studies in non- African Americans and Latinos, our
data showed that a decreased GFR was not an independent risk factor for
stroke in our patient population. In a recent large prospective cohort
study of AF patients, Go et al found that a lower level of estimated
glomerular filtration rate was associated with a graded, increased risk
of ischemic stroke and other systemic embolism, independently of known
risk factors in AF (30). A study performed in Japan evaluated if CKD
constitutes a risk for stroke and it concluded that decreased kidney
function increases the risk of first symptomatic stroke events in a
general Japanese population (31). Piccini et al reported that adding
impaired renal function to standard stroke risk scoring scale was a
potent predictor for stroke and systemic embolism in a predominantly
white population (22).
Multiple studies have demonstrated that stroke rates are higher in AF
patients with renal dysfunction. Vazquez et al demonstrated a 9.8-fold
increased risk of ischemic stroke among patients undergoing dialysis who
had AF compared those who maintained sinus rhythm during dialysis (32).
In the U.S. Renal Data System study, patients with end-stage renal
failure and AF had a 1.8-fold higher rate of ischemic strokes, whereas
hemorrhagic stroke rates were comparable to end-stage renal failure
patients in sinus rhythm (33). Conversely, in the Rotterdam study (34),
decreased GFR did not significantly increase the risk of ischemic
stroke, but was a strong predictor of hemorrhagic stroke. Genovesi et al
demonstrated that AF was associated with greater total and
cardiovascular mortality among hemodialysis patients and was more
notable for cardiovascular than non-cardiovascular mortality (8).
Nakagawa et al demonstrated that combined eGFR and
CHADS2 score could be an independent powerful predictor
of cardiovascular events and mortality in patients with NVAF (35).
Long-term mortality, cardiac events, and stroke risk were
>8 times higher when decreased eGFR was present with higher
CHADS2 score (≥2).
The mechanism by which chronic kidney disease (CKD) increases the risk
of MACE is not known. CKD increases vascular calcification,
inflammation, valve problems, and fluctuation in electrolytes,
sympathetic nervous system activation and modulation of renin
angiotensin system. Tanaka (36) noted an inverse relationship of eGFR to
thrombin-antithrombin (TAT) and fibrin D-dimer levels, both indexes of
thrombogenesis. Shlipak demonstrated that renal insufficiency was
independently associated with elevations in inflammatory and
pro-coagulant biomarkers (37). These findings lend support to the notion
that enhanced coagulation activation appears to be related to a
reduction in residual renal function in patients with AF (38).
A manual review of EMR was performed for all patients included in the
study to avoid false positives and negative. However, our study has
several limitations. It was completed at one center and was done
primarily on African American and Latino patient population. The
Latino/Hispanic population was not sub-stratified further and there have
been differences in prevalence in various subgroups (5). This was a
retrospective analysis of such patients. The contradictory result for
CKD being an independent risk factor for stroke could be due to our
unique patient population, or a relatively small sample size of patients
with paroxysmal AF mistakenly excluded from study.
A prospective study in minority AF patients with renal dysfunction
should be done in the future to provide further evidence regarding
ischemic neurological events in this patient population and verify our
findings of MACE.