Dataset Information

Genetic Association of Albuminuria with Cardiometabolic Disease and Blood Pressure.

ABSTRACT: Excretion of albumin in urine, or albuminuria, is associated with the development of multiple cardiovascular and metabolic diseases. However, whether pathways leading to albuminuria are causal for cardiometabolic diseases is unclear. We addressed this question using a Mendelian randomization framework in the UK Biobank, a large population-based cohort. We first performed a genome-wide association study for albuminuria in 382,500 individuals and identified 32 new albuminuria loci. We constructed albuminuria genetic risk scores and tested for association with cardiometabolic diseases. Genetically elevated albuminuria was strongly associated with increased risk of hypertension (1.38 OR; 95% CI, 1.27-1.50 per 1 SD predicted increase in albuminuria, p = 7.01 × 10-14). We then examined bidirectional associations of albuminuria with blood pressure which suggested that genetically elevated albuminuria led to higher blood pressure (2.16 mmHg systolic blood pressure; 95% CI, 1.51-2.82 per 1 SD predicted increase in albuminuria, p = 1.22 × 10-10) and that genetically elevated blood pressure led to more albuminuria (0.005 SD; 95% CI 0.004-0.006 per 1 mmHg predicted increase in systolic blood pressure, p = 2.45 × 10-13). These results support the existence of a feed-forward loop between albuminuria and blood pressure and imply that albuminuria could increase risk of cardiovascular disease through blood pressure. Moreover, they suggest therapies that target albuminuria-increasing processes could have antihypertensive effects that are amplified through inhibition of this feed-forward loop.

SUBMITTER: Haas ME

PROVIDER: S-EPMC6174360 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Genetic Association of Albuminuria with Cardiometabolic Disease and Blood Pressure.

Haas Mary E ME Aragam Krishna G KG Emdin Connor A CA Bick Alexander G AG Hemani Gibran G Davey Smith George G Kathiresan Sekar S

American journal of human genetics 20180913 4

Excretion of albumin in urine, or albuminuria, is associated with the development of multiple cardiovascular and metabolic diseases. However, whether pathways leading to albuminuria are causal for cardiometabolic diseases is unclear. We addressed this question using a Mendelian randomization framework in the UK Biobank, a large population-based cohort. We first performed a genome-wide association study for albuminuria in 382,500 individuals and identified 32 new albuminuria loci. We constructed ...[more]

PMID: 30220432

Similar Datasets

Project description:BACKGROUND: The relationship between hypertension and kidney disease is complicated. Clinical trials found intense blood pressure control was not associated with alterations in glomerular filtration rate (GFR) in all patients but did slow the rate of GFR decline among those with a higher baseline proteinuria. However, the underlying mechanism has been unclear. METHODS: We tested the hypothesis that the association between high blood pressure and renal function is modified by albuminuria status by conducting analyses in a cross-sectional study with 12,440 adult participants without known kidney diseases, diabetes or cardiovascular diseases, participating in the National Health and Nutrition Examination Survey (NHANES) 1999-2006. RESULTS: 1226 out of 12440 were found to have unknown high blood pressure and 4494 were found to have reduced renal function. Overall, a moderate association was found between high blood pressure and renal function insufficiency in all participants analyzed. However, among participants with albuminuria, the prevalence of moderate-severe renal insufficiency substantially and progressively increased from normal subjects to prehypertensive and undiagnosed hypertensive subjects (1.43%, 3.44%, 10.96%, respectively, P for trend<0.0001); on the other hand, the prevalence of undiagnosed hypertension was also significantly higher among subjects with moderate-severe renal insufficiency than those with mild renal insufficiency (35.54% Vs 19.09%, P value <0.05), supporting an association between hypertension and renal function damage. In contrast, no association between hypertension and renal insufficiency was observed among those without albuminuria in this population. Similar findings were observed when the CKD-EPI equation was used. CONCLUSIONS: The association between high blood pressure and reduced renal function could be dependent upon the albuminuria status. This finding may provide a possible explanation for results observed in clinical trials of intensive blood pressure control. Further studies are warranted to confirm our findings.

Project description:BackgroundCurrent guidelines recommend treating hypertension in patients with peripheral artery disease (PAD) to reduce the risk of cardiac events and stroke, but the effect of reducing blood pressure on lower extremity PAD events is largely unknown. We investigated the association of blood pressure with lower extremity PAD events using data from the ALLHAT trial (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial).MethodsALLHAT investigated the effect of different antihypertensive medication classes (chlorthalidone, amlodipine, lisinopril, or doxazosin) on cardiovascular events. With the use of these data, the primary outcome in our analysis was time to first lower extremity PAD event, defined as PAD-related hospitalization, procedures, medical treatment, or PAD-related death. Given the availability of longitudinal standardized blood pressure measurements, we analyzed systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure as time-varying categorical variables (reference categories 120-129 mm Hg for SBP, 70-79 mm Hg for DBP, and 45-54 mm Hg for pulse pressure) in separate models. We used extended Cox regression with death as a competing risk to calculate the association of each blood pressure component with PAD events, and report the results as subdistribution hazard ratios and 95% CIs.ResultsThe present analysis included 33 357 patients with an average age of 67.4 years, 53.1% men, 59.7% white race, and 36.2% with diabetes mellitus. The median baseline blood pressure was 146/84 mm Hg. Participants were followed for a median of 4.3 (interquartile range, 3.6-5.3) years, during which time 1489 (4.5%) had a lower extremity PAD event, and 4148 (12.4%) died. In models adjusted for demographic and clinical characteristics, SBP <120 mm Hg was associated with a 26% (CI, 5%-52%; P=0.015) higher hazard and SBP≥160 mm Hg was associated with a 21% (CI, 0%-48%; P=0.050) higher hazard for a PAD event, in comparison with SBP 120 to 129 mm Hg. In contrast, lower, but not higher, DBP was associated with a higher hazard of PAD events: for DBP <60 mm Hg (hazard ratio, 1.72; CI, 1.38-2.16). Pulse pressure had a U-shaped association with PAD events.ConclusionsIn this reanalysis of data from ALLHAT, we found a higher rate of lower extremity PAD events with higher and lower SBP and pulse pressure and with lower DBP. Given the recent revised blood pressure guidelines advocating lower SBP targets for overall cardiovascular risk reduction, further refinement of optimal blood pressure targets specific to PAD is needed.Clinical trial registrationURL: https://www.clinicaltrials.gov . Unique identifier: NCT00000542.

Dataset Information

Genetic Association of Albuminuria with Cardiometabolic Disease and Blood Pressure.

Publications

Genetic Association of Albuminuria with Cardiometabolic Disease and Blood Pressure.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets