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Plasma lactate and incident hypertension in the atherosclerosis risk in communities study.

ABSTRACT: Recent evidence suggests that insufficient oxidative capacity or mitochondrial dysfunction may play a causal role in the development of high blood pressure. However, this hypothesis has not been tested in the general population. We hypothesized that lactate, a measure of oxidative capacity, would be positively associated with incident hypertension even after accounting for traditional hypertension risk factors.Plasma lactate was measured in 5,554 participants from the Atherosclerosis Risk in Communities (ARIC) Study with no subclinical or diagnosed hypertension at baseline (1996-1998). Incident hypertension was defined by self-report or hypertension medication use. Analyses were performed with Cox proportional hazards models.The mean age was 61.9 years, and the mean lactate was 0.8 mmol/L. During a median follow-up period of 11.9 years (range = 26.9 days to 13.4 years), there were 3,849 new cases of hypertension. The fourth quartile of lactate (compared with the first quartile) was associated with an elevated risk of hypertension (hazard ratio (HR) = 1.18; 95% confidence interval (CI) = 1.07-1.31) even after adjustment for traditional risk factors, including baseline systolic and diastolic blood pressure. This association was stronger when the population was restricted to participants with normal blood pressure (<120mm Hg/<80mm Hg; HR = 1.42; 95% CI = 1.23-1.63). In strata of sex, the association was strong in women vs. null in men (P interaction = 0.01).Plasma lactate is associated with incident hypertension in women, especially with a normal blood pressure (<120mm Hg/<80mm Hg). Future studies should elucidate the mechanisms underlying these observations.

SUBMITTER: Juraschek SP

PROVIDER: S-EPMC4357800 | biostudies-other | 2015 Feb

REPOSITORIES: biostudies-other

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Plasma lactate and incident hypertension in the atherosclerosis risk in communities study.

Juraschek Stephen P SP Bower Julie K JK Selvin Elizabeth E Subash Shantha Ghanshyam Palamaner GP Hoogeveen Ron C RC Ballantyne Christie M CM Young J Hunter JH

American journal of hypertension 20140703 2

<h4>Background</h4>Recent evidence suggests that insufficient oxidative capacity or mitochondrial dysfunction may play a causal role in the development of high blood pressure. However, this hypothesis has not been tested in the general population. We hypothesized that lactate, a measure of oxidative capacity, would be positively associated with incident hypertension even after accounting for traditional hypertension risk factors.<h4>Methods</h4>Plasma lactate was measured in 5,554 participants f ...[more]

PMID: 24994607

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Project description:IMPORTANCE:Studies document a progressive increase in heart disease risk as systolic blood pressure (SBP) rises above 115 mm Hg, but it is unknown whether an SBP lower than 120 mm Hg among adults with hypertension (HTN) lowers heart failure, stroke, and myocardial infarction risk. OBJECTIVE:To examine the risk of incident cardiovascular (CV) events among adults with HTN according to 3 SBP levels: 140 mm Hg or higher; 120 to 139 mm Hg; and a reference level of lower than 120 mm Hg. DESIGN, SETTING, AND PARTICIPANTS:A total of 4480 participants with HTN but without prevalent CV disease at baseline (years 1987-1989) from the Atherosclerosis Risk in Communities Study were included. Measurements of SBP were taken at baseline and at 3 triennial visits; SBP was treated as a time-dependent variable and categorized as elevated (?140 mm Hg), standard (120-139 mm Hg), and low (<120 mm Hg). Multivariable Cox regression models included baseline age, sex, diabetes status, BMI, high cholesterol level, smoking status, and alcohol intake. MAIN OUTCOMES AND MEASURES:Incident composite CV events (heart failure, ischemic stroke, myocardial infarction, or death related to coronary heart disease). RESULTS:After a median follow-up of 21.8 years, a total of 1622 incident CV events had occurred. Participants with elevated SBP developed incident CV events at a significantly higher rate than those in the low BP group (adjusted hazard ratio [HR], 1.46; 95% CI, 1.26-1.69). However, there was no difference in incident CV event-free survival among those in the standard vs low SBP group (adjusted HR, 1.00; 95% CI, 0.85-1.17). Further adjustment for BP medication use or diastolic BP did not significantly affect the results. CONCLUSIONS AND RELEVANCE:Among patients with HTN, having an elevated SBP carries the highest risk for cardiovascular events, but in this categorical analysis, once SBP was below 140 mm Hg, an SBP lower than 120 mm Hg did not appear to lessen the risk of incident CV events.

Project description:Decreased kidney function and kidney damage may predate hypertension, but only a few studies have investigated both types of markers simultaneously, and these studies have obtained conflicting results.Cross-sectional for prevalent and prospective observational study for incident hypertension.9,593 participants from the ARIC (Atherosclerosis Risk in Communities) Study, aged 53-75 years in 1996-1998.Several markers of kidney function (estimated glomerular filtration rate using serum creatinine and/or cystatin C and 2 novel markers [?-trace protein and ?2-microglobulin]) and 1 marker of kidney damage (urinary albumin-creatinine ratio [ACR]). Every kidney marker was categorized by its quintiles (top quintile as a reference for estimated glomerular filtration rates and bottom quintile for the rest).Prevalent and incident hypertension.Prevalence ratios and HRs of hypertension based on modified Poisson regression and Cox proportional hazards models, respectively.There were 4,378 participants (45.6%) with prevalent hypertension at baseline and 2,175 incident hypertension cases during a median follow-up of 9.8 years. Although all 5 kidney function markers were associated significantly with prevalent hypertension, prevalent hypertension was associated most notably with higher ACR (adjusted prevalence ratio, 1.60 [95% CI, 1.50-1.71] for the highest vs lowest ACR quintile). Similarly, ACR was associated consistently with incident hypertension in all models tested (adjusted HR, 1.28 [95% CI, 1.10-1.49] for top quintile), while kidney function markers demonstrated significant associations in some, but not all, models. Even mildly increased ACR (9.14-14.0mg/g) was associated significantly with incident hypertension.Self-reported use of antihypertensive medication for defining incident hypertension, single assessment of kidney markers, and relatively narrow age range.Although all kidney markers were associated with prevalent hypertension, only elevated albuminuria was associated consistently with incident hypertension, suggesting that kidney damage is related more closely to hypertension than moderate reduction in overall kidney function.

Project description:Carotid intima-media thickness has been reported to predict kidney function decline. However, whether carotid intima-media thickness is associated with a hard kidney end point, ESRD, has not been investigated.We studied 13,197 Atherosclerosis Risk in Communities participants at visit 1 (1987-1989) without history of cardiovascular disease, including coronary heart disease, stroke, and heart failure, at baseline and assessed whether carotid intima-media thickness measured by B-mode ultrasound is associated with ESRD risk using Cox proportional hazards models. Regarding carotid intima-media thickness parameters, we investigated the mean and maximum values of overall and segment-specific (common, bifurcation, and internal carotid arteries) measurements.Mean age was 54.0 (SD=5.7) years old, and there were 3373 (25.6%) blacks and 7370 (55.8%) women. During a median follow-up of 22.7 years, 433 participants developed ESRD (1.4/1000 person-years). After adjusting for shared risk factors for atherosclerosis and kidney disease, including baseline kidney function, carotid intima-media thickness was significantly associated with ESRD risk (hazard ratio [HR] between quartiles 4 and 1, 1.46; 95% confidence interval [95% CI], 1.02 to 2.08 for overall mean intima-media thickness and HR between quartiles 4 and 1, 1.75; 95% CI, 1.24 to 2.48 for overall maximum intima-media thickness). The associations were largely consistent in demographic and clinical subgroups. When we explored segment-specific intima-media thicknesses, the associations with ESRD were most robust for bifurcation carotid (e.g., adjusted HR between quartiles 4 and 1 of mean intima-media thickness, 1.49; 95% CI, 1.04 to 2.13 for bifurcation; adjusted HR between quartiles 4 and 1 of mean intima-media thickness, 1.36; 95% CI, 0.94 to 1.97 for common; and adjusted HR between quartiles 4 and 1 of mean intima-media thickness, 0.93; 95% CI, 0.67 to 1.29 for internal).Carotid intima-media thickness was independently associated with incident ESRD in the general population, suggesting the shared etiology of atherosclerosis and ESRD.

Dataset Information

Plasma lactate and incident hypertension in the atherosclerosis risk in communities study.

Publications

Plasma lactate and incident hypertension in the atherosclerosis risk in communities study.

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