April 30, 2012 (London, United Kingdom) — Several new studies presented at the European Society of Hypertension (ESH) European Meeting on Hypertension 2012 indicate that uric-acid levels are associated with hypertension, diabetes, and a range of other CVD risk factors.

In the first presentation, during the late-breaking clinical-trials session on Friday, Dr Adi Leiba (Chaim Sheba Medical Center, Tel Hashomer, Israel) presented data on more than 100 000 people with uric-acid measurements from an Israeli health maintenance organization (HMO) [1]. He showed that those with so-called "normal" levels of uric acid had a 50% higher risk of hypertension and an almost doubling of diabetes over 10-year follow-up, compared with those who have naturally occurring low levels of uric acid--a phenomenon that exists in certain Jewish families.

Leiba said that even presumably "normal" uric-acid levels, "normal goutwise and kidney-stone–wise," are "probably not normal cardiovascularwise. So the question is, is uric acid a friend or a foe? It's probably a foe; it's probably a cause of cardiovascular disease, and definitely it's not such an innocent bystander," he observed.

Is uric acid a friend or a foe? It's probably a foe; it's probably a cause of cardiovascular disease.

Commenting on the presentation, Dr Gary Jennings (Baker ID Heart and Diabetes Institute, Melbourne, Australia) told heartwire : "I thought it was very interesting because it's a long-term follow-up, with big numbers." The uric-acid story "has been around for years," says Jennings, and "there's always this chicken-and-egg question with uric acid and BP and kidney disease. This was quite a neat and very simple approach to take people at the low end and see what happens."

Normal vs Low Uric Acid=50% Increased Risk of Hypertension

High uric-acid levels are correlated with cardiovascular risk, but it is as-yet unclear whether uric acid is a culprit, a risk factor, or just a surrogate of disease, Leiba told the conference. He explained that there are a number of Jewish families that have naturally occurring low levels of uric acid, so he and his colleagues decided to compare these individuals with people who had so-called "normal" levels, instead of the usual practice of comparing normal with high levels.

Using the electronic database of the HMO, Clalit, starting in 2002, Leiba et al compared a historical cohort of healthy adults (40–70 years) with low uric-acid levels (<3 mg/dL) with those who had normal values (3.1–6.8 mg/dL) during 10 years of follow-up. They excluded patients who had diabetes, hypertension, ischemic heart disease, congestive heart failure, chronic kidney disease, cerebrovascular or peripheral vascular disease or who used diuretics, cardiac medications, aspirin, probenecid, or allopurinol.

Serum uric-acid levels <3 mg/dL were found in 9156 subjects, mostly women, and these were compared with almost 114 000 subjects with normal values. There were some significant differences in metabolic parameters between the groups, but all were within the normal range.

I can't imagine putting people with normal uric acid on allopurinol, so it comes back to the usual kind of lifestyle advice.

After 10 years of follow-up, healthy subjects with normal uric-acid levels had a 53% higher risk of developing hypertension (HR 1.53; p<0.001) compared with the hypouricemic group, in a logistic regression model adjusted for sex, age, socioeconomic status, body-mass index (BMI), smoking, baseline estimated glomerular filtration rate (eGFR), glucose, and LDL and HDL levels.

And the risks of developing new-onset diabetes and chronic kidney disease were almost doubled (HR 1.84, p<0.001; and HR 1.93, p=0.055, respectively) in the normal-uric-acid-level group compared with the hypouricemic group.

Jennings observed that uric acid "is measured a lot, because it's part of a standard biochemistry panel." But the question remains, he says: "What do you do about it? I can't imagine putting people with normal uric acid on allopurinol, so it comes back to the usual kind of lifestyle advice."

Threefold Increased Risk of High LVMI in Those With Uric Acid >8 mg/Dl

Separately, Dr Ayako Yoshimura (Kurume University School of Medicine, Japan) and colleagues performed a large-scale epidemiological study in a general population in Tanushimaru, Japan, in 2009 [2]. There were 1943 participants (774 males and 1169 females) aged over 40 years. Serum uric-acid and creatinine levels were measured, and all individuals underwent echocardiography, from which LVMI was calculated.

The LVMI was strongly and significantly associated with age, male gender, waist circumference, BMI, systolic and diastolic BP, and creatinine, among other things, and with uric acid (p<0.001).

In logistic regression analysis, the risk of left ventricular hypertrophy was almost threefold higher in those with uric-acid levels of >8 mg/dL, even after adjustment for confounding factors.

Patients With High LVMI by Uric-Acid Level

 

<3.9 mg/dL (reference)

4.0–4.9 mg/dL

5.0–5.9 mg/dL

6.9–7.9 mg/dL

>8.0 mg/dL

n

371

560

507

412

82

High left ventricular mass indexa, n (%)

42 (11.3)

69 (12.3)

79 (15.6)

57 (15.6)

19 (23.1)

Hazard ratiob

Ref

1.05

1.34

1.29

2.70c

a. Male >125g/m2; female >110 g/m2

b. Adjusted for age, sex, systolic blood pressure, BMI, and LVEF

c. p<0.05 vs group with <3.9 mg/dL

This study is the first demonstration of a positive relation between LVMI and uric acid in a general population.

"This study is the first demonstration of a positive relation between LVMI and uric acid in a general population," say the researchers, adding that their results also indicate that uric acid may be a component or marker of metabolic syndrome.

And other research [3], also presented as a poster by Dr MV Papavasileiou (Sismanoglio General Hospital, Athens, Greece) and colleagues, found that in 874 hypertensive patients, uric-acid blood levels correlated significantly with all components of the metabolic syndrome.

Several other abstracts presented over the course of the three-day ESH meeting reported associations between high uric-acid levels and other cardiovascular-risk parameters in hypertensive patients, including arterial stiffness, microalbuminuria, microvascular endothelial vasomotor function, and atheromatosis of the carotid artery.

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