serum urate levels and incident gout over 11 years
A large individual participant data analysis documented a strong nonlinear relationship between serum urate levels and developing clinical gout (see gout serum urate conc and gout annrheumdis2018 in dropbox, or Dalbeth N. Ann Rheum Dis 2018; 77: 1048).
Details:
-- 4 longitudinal observational studies fit the criteria for inclusion: the Atherosclerosis Risk in Communities Study (ARIC) with 10,775 participants; the Coronary Artery Risk Development in Young Adults Study (CARDIA) with 3470 participants; and both the Original and Offspring cohorts of the Framingham Heart Study (FHS)
-- all studies had publicly-available patient-level data, incident gout data, serum urate levels measured prior to assessment of incident gout, minimum study duration of 3 years, and gout defined by using recognized criteria/doctor diagnosis/patient self-reported disease/or self-reported of doctor diagnosis
-- there was a total of 18,889 people who were gout-free at baseline with mean of 11.2 years of follow-up: 212,363 total patient-years
-- 43.8% men, mean age 49 (17-85)
Results:
-- overall cumulative incidence of gout for all participants:
-- 0.6% at 3 years, 1.1% at 5 years, 2.4% at 10 years, 3.2% at 15 years
-- urate-specific gout incidence overall (primary outcome):
-- by 5 years: 0.33% for baseline serum urate <6 mg/dL up to 26% if ≥10 mg/dL
-- by 10 years: 0.79% for baseline serum urate <6 , up to 40% if ≥10 mg/dL
-- by 15 years: 1.1% for baseline serum urate <6 , up to 49% if ≥10 mg/dL
-- per the 5-year data, the incidence of gout was:
-- for those with serum urate ≥7, incidence ago was 9.8/1000 person-years
-- for those with serum urate ≥8, incidence ago was 20/1000 person-years
-- for those with serum urate ≥9, incidence ago was 34/1000 person-years
-- for those with serum urate ≥10, incidence ago was 53/1000 person-years
-- for women, the cumulative incidence of gout per baseline serum urate measurement was lower by 3 years of follow-up, but by 10 to 15 years of follow-up the cumulative incidence was the same as men
-- relative risk of developing gout, as compared to a baseline serum urate level <6 mg/dL (all with p<0.001), the hazard ratio (HR), adjusted for age, sex, ethnicity, and cohort were:
-- for baseline serum urate HR 6.0-6.9 was 2.7 (2.0-3.6)
-- for baseline serum urate HR 7.0-7.9 was 6.6 (5.0-8.8)
-- for baseline serum urate HR 8.0-8.9 was 15 (11-20)
-- for baseline serum urate HR 9.0-9.9 was 30 (21-42)
-- adjusted HR for baseline serum urate ≥10 was 64 (43-96)
Commentary:
-- the study revealed a strong non-linear concentration-dependent relationship between serum urate levels and incident gout
-- the overall prevalence of hyperuricemia is increasing in the US, as documented by the National Health and Nutrition Examination Survey.
-- there are an array of risk factors associated with increased uric acid levels:
-- several foods/drinks lead to hyperuricemia: alcohol, high purine diet
(meat/seafoods), as well as obesity.
-- one
other major dietary factor leading to hyperuricemia is fructose. --I’ve seen several patients stop drinking sodas (a large source of high fructose corn syrup) and have their serum uric acid levels decrease by 1-1.5 mg/dL (as commented on in http://gmodestmedblogs.blogspot.com/2016/12/new-gout-management-guidelines.html .
--Another blog (http://gmodestmedblogs.blogspot.com/2015/11/fructose-restriction-and.html ) did not find a lowering of uric acid by diet in a small study of kids, though this blog reviews some of the epidemiologic studies.
--Also http://gmodestmedblogs.blogspot.com/2016/08/non-alcoholic-fatty-liver-disease-2.html has a review of fructose metabolism (different than other sugars) and suggestions that it may directly lead to non-alcoholic fatty liver disease.
-- Medications: a study of 25K pts in general practices in UK
found a 19% decreased risk of clinical gout with losartan (compared
to other hypertensive pts), 13% with ccbs (21% decreased with amlodipine, 13%
with nifedipine, and 14% with diltiazem), and increased gout risk with
diuretics, b-blockers, ACE-I's, other ARBs besides losartan. They
note in their discussion some studies (which I looked at, and are pretty
small…) find that ccbs (esp nifedipine and amlodipine)
and losartan are uricosuric and decrease serum uric acid
levels. See https://www.bmj.com/content/bmj/344/bmj.d8190.full.pdf
.
--
as per the authors, the current study was limited by lack of environmental risk
factors which could have influenced gout or the inflammatory response to
hyperuricemia (since only half the patients with very high uric acid levels
develop clinical gout, were there some moderators for inciting or depressing
clinical gout?). and there were variable differences in the definitions and
ascertainment of the gout diagnosis; there was only one baseline serum urate
concentration measured (this might have changed over time), and this study
looked only at gout as the clinical outcome and not other perhaps more
important endpoints such as hypertension, chronic kidney disease, or
cardiovascular disease
--and there are a lot of
relevant blogs reviewing studies, some related to the potential effects of
hyperuricemia on heart disease and hypertension, and some suggesting that gout
therapies may lower the risk.
--see http://gmodestmedblogs.blogspot.com/2017/07/hyperuricemia-and-cardiometabolic.html
: a Japanese study suggesting that hyperuricemia predated the
development of hypertension, hyperlipidemia, chronic kidney disease,
overweight/obesity, diabetes
--see http://gmodestmedblogs.blogspot.com/2016/03/hyperuricemia-allopurinol-decreases.html for a Danish study suggesting that treating hyperuricemia in those
with allopurinol led to fewer cardiovascular events
--see http://gmodestmedblogs.blogspot.com/search/label/gout%2Fhyperuricemia which includes blog on an interesting evolutionary perspective on
hyperuricemia (see http://gmodestmedblogs.blogspot.com/2019/04/uric-acid-lowering-cardiovasc-benefit.html ), as well as several on gout (guidelines, even a
study suggesting that colchicine lowers cardiovascular risk)
So,
I have become more convinced that hyperuricemia may well be a bad actor for a
lot of chronic medical problems, as well as clinical gout. It may be
useful to occasionally check uric acid levels on patients (I do, but this is
certainly not routine clinical practice), with an eye to decreasing causative
agents if the uric acid is elevated (dietary changes, with a focus on high
fructose corn syrup), perhaps switching antihypertensive agents to using more
losartan, ccb’s. and strongly considering allopurinol if very elevated levels.
geoff
If you
would like to be on the regular email list for upcoming blogs, please contact
me at gmodest@uphams.org
to get
access to blogs since 8/15/17:
2.
click on 3 parallel lines top left, if you want to see blogs by category, then
click on "labels" and choose a category
3. or
you can just type in a name in the search box and get all the blogs with that
name in them
to
access older blogs from the BMJ website, from October 2013 until 8/15/17: go
to http://blogs.bmj.com/bmjebmspotlight/category/archive/
please
feel free to circulate this to others. also, if you send me their emails, i can
add them to the list
Comments
Post a Comment
if you would like to receive the near-daily emails regularly, please email me at gmodest@uphams.org