Relationship Between Hyperuricemia and Cardiovascular Disease Risk Factors in a Chinese Population: A Cross-Sectional Study

To study the relationship between hyperuricemia and cardiovascular diseases (CVDs) risk factors in a Chinese population.  Data analyzed in this study were from the Chinese Hyperuricemia and Gout Database. Indicators of serum uric acid (SUA) level, height, weight, systolic blood pressure (SBP), diastolic blood pressure (DBP), smoking status, alcohol consumption, blood glucose, cholesterol, and triglycerides were measured. T test, one-way analysis of variance, Pearson’s correlation, multivariate linear regression, and multivariate logistic regression were used.  Compared with normouricemic men, hyperuricemic men had greater height (P<0.01), weight (P<0.001), body mass index (BMI) (P<0.001), SBP (P<0.01), DBP (P<0.001), cholesterol (P<0.01), and triglyceride (P<0.001). Compared with normouricemic women, hyperuricemic women were older (P<0.01) and had greater weight (P<0.05), BMI (P<0.01), SBP (P<0.01), DBP (P<0.05), glucose (P<0.05), and triglyceride (P<0.001). In men, an increase of 1 mg/dL in SUA was associated with a 0.279 kg/m2 increase in BMI (P<0.001), a 2.438 mg/dL increase in cholesterol (P<0.05), a 10.358 mg/dL increase in triglyceride (P<0.001), and a 3.1 mg/dL decrease in glucose (P<0.01). In women, an increase of 1 mg/dL SUA was associated with a 0.168 kg/m2 increase in BMI (P<0.01) and a 3.708 mg/dL increase in triglyceride (P<0.01). After adjustment, SUA was strongly associated with obesity and hyperlipidemia in both sexes.  Elevated serum uric acid concentration was strongly associated with obesity and hyperlipidemia in both men and women. These results indicated that, among hyperuricemia patients, we should pay more attention to the possibility of cardiovascular complications. These results might provide a novel target or a possible new treatment for cardiovascular diseases by lowering the level of serum uric acid.

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Because previous studies (2, 3, 7, 21) have suggested that uric acid is more strongly associated with adverse events in women than in men, we chose a priori to perform sex-specific analyses.  Study Sample The selection criteria and study design of the Framingham Heart Study and the Framingham Offspring Study have been described elsewhere (22, 23). Original participants of the Framingham Heart Study who took part in the 13th biennial examination (1972 to 1976) and adult participants in the first examination of the Framingham Offspring Study (1971 to 1975) were eligible for this investigation (n=7940). Blood samples for uric acid measurement were obtained in 7650 (96.3%) persons. Participants were excluded (n=887) for the following reasons: use of more than 2 g of salicylates per day (n=17), missing covariate or follow-up data (n=117), and prevalent cardiovascular disease (n=753). The remaining 6763 participants were followed prospectively until 1994. 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Menopause was defined as the absence of menses for 1 year or more. Diabetes was defined on the basis of a nonfasting blood glucose level of 11.1 mmol/L (200 mg/dL) or greater, a fasting blood glucose level of 7.8 mmol/L (140 mg/dL) or greater, or the use of insulin or an oral hypoglycemic agent. Serum uric acid levels were measured with an autoanalyzer that used a phosphotungstic acid reagent (25). Cholesterol levels were determined according to the Abell-Kendall method (26). Outcome Events The primary outcome measures were incident coronary heart disease events, death from cardiovascular disease (coronary heart disease, congestive heart failure, stroke, or other cardiovascular disease), and death from all causes. Coronary heart disease events included the following: death from coronary heart disease (available information suggested coronary heart disease as the probable cause), recognized myocardial infarction (serial electrocardiographic changes leading to development of new pathologic Q waves, characteristic increase and decrease in serum myocardial markers with a suggestive clinical history, or evidence at necropsy of new or recent infarction), and coronary insufficiency (prolonged ischemic chest discomfort associated with transient repolarization abnormality, without criteria for myocardial infarction). Events that were more equivocal, such as unrecognized myocardial infarction and angina pectoris, were not included as coronary heart disease events for this analysis. A panel of three physicians determined the outcome events according to previously published criteria (27) after reviewing Framingham Heart Study and outside hospital and physician records. Statistical Analysis Separate analyses were performed for men and women. All participants were divided according to sex-specific uric acid quintiles. Crude event rates were calculated for each quintile. Cox proportional-hazards regression models (28) were used to examine the relations of uric acid quintiles (with quintile 1 as the reference category) and the relation of uric acid level as a continuous variable to incidence of coronary heart disease events, cardiovascular disease mortality rates, and all-cause mortality rates. For comparative purposes, hazard ratios were calculated without adjustment. For inferential purposes, hazard ratios were calculated with adjustment for age only and also with adjustment for age and other clinical variables associated with uric acid level or atherosclerotic events: body mass index (kg/m2), diabetes (yes/no), systolic blood pressure (mm Hg), current diuretic use (yes/no), use of antihypertensive medications other than diuretics (yes/no), left ventricular hypertrophy shown on electrocardiography (yes/no), total cholesterol level (mmol/L), smoking status (yes/no), alcohol use (ounces consumed per week), and menopausal status in women (yes/no). Post hoc subgroup analyses were done to determine any possible relations between quintiles of uric acid and the outcome events in participants stratified according to diuretic use and hypertension status. All analyses were performed on a Sun UltraSPARC computer (Sun Microsystems, Mountain View, California) using SAS software (SAS Institute, Cary, North Carolina) (29). A two-sided P value less than 0.05 was the criterion for statistical significance.  Participant Characteristics Table 1 shows the baseline clinical characteristics for men and women. The mean uric acid level was 379 mol/L in men (range, 119 to 738 mol/L) and 285 mol/L in women (range, 24 to 696 mol/L). The effect of age on mean serum uric acid level is illustrated in the Figure. In men, uric acid levels changed minimally with age. In women, mean serum uric acid levels gradually increased from the fourth to the seventh decades of life. Furthermore, among women 30 to 54 years of age, the mean serum uric acid level was 5 to 13 mol/L greater in those who were postmenopausal (data not shown). Table 1. Baseline Clinical Characteristics Figure. Mean serum uric acid level by sex and 5-year age group. Uric Acid Level and Outcome Events There were 117 376 person-years of follow-up. In men, 394 coronary heart disease events, 232 deaths due to cardiovascular disease, and 729 deaths from all causes occurred. As a continuous variable, baseline uric acid level was not associated with increased risk for any end point in men. In fully adjusted Cox models, for every 60-mol/L increase in serum uric acid level, hazard ratios were as follows: 0.91 (95% CI, 0.83 to 0.99) for coronary heart disease, 0.95 (CI, 0.86 to 1.06) for death from cardiovascular disease, and 0.97 (CI, 0.91 to 1.03) for death from all causes. In men, baseline quintile of serum uric acid level was also not associated with increased risk for any outcome measure. Uric acid level was inversely related to coronary heart disease in the full multivariable adjusted model (Table 2). Table 2. Relations of Serum Uric Acid Level to Coronary Heart Disease, Death from Cardiovascular Disease, and Death from All Causes In women, 223 coronary heart disease events, 197 deaths from cardiovascular disease, and 731 deaths from all causes occurred. From quintile 1 to quintile 5, crude rates increased more than threefold for coronary heart disease (from 1.9 to 7.5 per 1000 person-years), death from cardiovascular disease (from 1.3 to 7.0 per 1000 person-years) and death from all causes (from 6.3 to 21.8 per 1000 person-years) (Table 2). In unadjusted Cox models in which quintile 1 was the reference category, risk significantly increased with increasing uric acid quintile for all three outcome measures (P<0.001 for trend). This trend diminished after adjustment for age but remained significant for coronary heart disease (P=0.002), death from cardiovascular disease (P=0.009), and death from all causes (P=0.03). In fully adjusted Cox models, baseline uric acid level was no longer associated with increased risk for coronary heart disease (P>0.2 for trend), death from cardiovascular disease (P=0.23), or death from all causes (P>0.2). Similar relations were found when baseline uric acid level was assessed as a continuous variable. In the fully adjusted models, hazard ratios for every 60-mol/L increase in serum uric acid level were as follows: 1.05 (CI, 0.94 to 1.17) for coro

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title: Serum uric acid and cardiovascular disease: recent developments, and where do they leave us?
abstract: The relationship between serum uric acid (SUA) and cardiovascular disease has been controversial. Here we review recent literature assessing whether hyperuricemia is an independent risk factor for adverse cardiovascular outcomes. Studies from the past 6 years evaluating the association of SUA with cardiovascular disease were identified through MEDLINE, EMBASE, and Cochrane library searches, bibliography cross-referencing, and review articles. Twenty-one cohort studies in healthy and high-risk patients with cardiovascular disease were identified and reviewed. In studies of high-risk patients, in which more overall events were recorded, 10 of 11 studies were supportive of an independent association. In 10 studies of healthy patients, 6 suggested an independent association of SUA with adverse cardiovascular outcomes. Increasing SUA is likely an independent risk factor for cardiovascular disease in high-risk individuals. However, the magnitude of excess risk attributable to high SUA is likely to be small in healthy individuals. Trials of SUA-lowering therapy in hyperuricemic patients evaluating the effect on cardiovascular outcomes are justified in high-risk patients.

title: The impact of serum uric acid on cardiovascular outcomes in the LIFE study.
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title: Cardiovascular Tissue Engineering: Where We Come From and Where Are We Now?
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title: Relations of hyperuricemia with the various components of the insulin resistance syndrome in young black and white adults: the CARDIA study. Coronary Artery Risk Development in Young Adults.
abstract: To assess the association of hyperuricemia with the various components of the Insulin Resistance Syndrome (IRS) in a biracial cohort of young adults.



Cross-sectional study in 4053 young black and white adults aged 18-30 years from the Coronary Artery Risk Development in Young Adults (CARDIA) study.



Body mass index (BMI), fasting insulin, and triglycerides were significantly higher, and high density lipoprotein (HDL)-cholesterol lower in subjects with hyperuricemia (uric acid > or = 7.0 mg/dl in males; > or = 6.0 mg/dl in females) (all p < 0.001). BMI showed the strongest positive correlation with uric acid among the IRS components. Significant associations of hyperuricemia with these risk factors were observed in all sex-race groups, which persisted after controlling for possible confounders including age, education, physical activity, smoking, alcohol intake, oral contraceptive use, and creatinine. Further adjustment for BMI and/or waist-to-hip ratio caused a large decrease in the strength of the associations. Adjustment for insulin also lead to decreases; however, the influence of fasting insulin appeared weaker than obesity. Even after controlling for obesity, insulin, and the other components of the IRS, male subjects in both races in the upper tertile of triglycerides were still more likely to have hyperuricemia.



The association of hyperuricemia with most aspects of the IRS may result predominantly from their covariation with adiposity and secondarily with insulin level. Elevated triglyceride level seems to have an independent relationship with hyperuricemia in males. The relationship between hyperuricemia and cardiovascular disease observed in previous studies may be secondary to its association with the IRS.

title: Prevalence of hyperuricemia and relation of serum uric acid with cardiovascular risk factors in a developing country
abstract: BackgroundThe prevalence of hyperuricemia has rarely been investigated in developing countries. The purpose of the present study was to investigate the prevalence of hyperuricemia and the association between uric acid levels and the various cardiovascular risk factors in a developing country with high average blood pressures (the Seychelles, Indian Ocean, population mainly of African origin).MethodsThis cross-sectional health examination survey was based on a population random sample from the Seychelles. It included 1011 subjects aged 25 to 64 years. Blood pressure (BP), body mass index (BMI), waist circumference, waist-to-hip ratio, total and HDL cholesterol, serum triglycerides and serum uric acid were measured. Data were analyzed using scatterplot smoothing techniques and gender-specific linear regression models.ResultsThe prevalence of a serum uric acid level >420 μmol/L in men was 35.2% and the prevalence of a serum uric acid level >360 μmol/L was 8.7% in women. Serum uric acid was strongly related to serum triglycerides in men as well as in women (r = 0.73 in men and r = 0.59 in women, p < 0.001). Uric acid levels were also significantly associated but to a lesser degree with age, BMI, blood pressure, alcohol and the use of antihypertensive therapy. In a regression model, triglycerides, age, BMI, antihypertensive therapy and alcohol consumption accounted for about 50% (R2) of the serum uric acid variations in men as well as in women.ConclusionsThis study shows that the prevalence of hyperuricemia can be high in a developing country such as the Seychelles. Besides alcohol consumption and the use of antihypertensive therapy, mainly diuretics, serum uric acid is markedly associated with parameters of the metabolic syndrome, in particular serum triglycerides. Considering the growing incidence of obesity and metabolic syndrome worldwide and the potential link between hyperuricemia and cardiovascular complications, more emphasis should be put on the evolving prevalence of hyperuricemia in developing countries.

title: Arsenic exposure, hyperuricemia, and gout in US adults.
abstract: There is very limited information on the association between arsenic and serum uric acid levels or gout. The aim of this study was to investigate the association of arsenic with hyperuricemia and gout in US adults.



A cross-sectional study was conducted in 5632 adults aged 20years or older from the National Health and Nutrition Examination Survey (NHANES) 2003-2010 with determinations of serum uric acid and urine total arsenic and dimethylarsinate (DMA). Hyperuricemia was defined as serum uric acid higher than 7.0mg/dL for men and 6.0mg/dL for women. Gout was defined based on self-reported physician diagnosis and medication use.



After adjustment for sociodemographic factors, comorbidities and arsenobetaine levels, the increase in the geometric means of serum uric acid associated with one interquartile range increase in total arsenic and DMA levels was 3% (95% CI 2-5) and 3% (2-5), respectively, in men and 1% (0-3) and 2% (0-4), respectively, in women. In men, the adjusted odds ratio for hyperuricemia comparing the highest to lowest quartiles of total arsenic was 1.84 (95% CI, 1.26-2.68) and for DMA it was 1.41 (95% CI, 1.01-1.96). The corresponding odds ratios in women were 1.26 (0.77, 2.07) and 1.49 (0.96, 2.31), respectively. The odds ratio for gout comparing the highest to lowest tertiles was 5.46 (95% CI, 1.70-17.6) for total arsenic and 1.98 (0.64-6.15) for DMA among women older than 40years old. Urine arsenic was not associated with gout in men.



Low level arsenic exposures may be associated with the risk of hyperuricemia in men and with the prevalence of gout in women. Prospective research focusing on establishing the direction of the relationship among arsenic, hyperuricemia, and gout is needed.

title: Metabolic Syndrome among Undergraduate Students Attending Medical Clinics for Obligatory Medical Screening
abstract: To determine the prevalence and risk factors for metabolic syndrome (MS) among first-year undergraduate students in three Sudanese universities.  A total of 384 first-year students attending university medical clinics for obligatory medical checkup in Khartoum, Sudan participated in this cross-sectional study. Anthropometric parameters, including weight, height, body mass index (BMI) and waist circumference (WC) were measured with reference to National Cholesterol Education Program’s Adult Treatment Panel III (NCEP/ATP III) guidelines. Fasting blood samples were collected from all participants and assayed for fasting blood glucose (FBG), total cholesterol (TC), triglyceride (TG), high density lipoprotein (HDL), and low density lipoprotein (LDL).  The overall prevalence of MS in the test group was 7.8 %. The prevalence of MS, though higher in females, was statistically not significant (p = 0.32). According to residential area (rural – urban), the prevalence was higher in urban than rural, 10.4 and 4.4 %, respectively (p = 0.25 and p = 0.25, respectively). In addition, frequency of MS was directly proportional to age. The weight of patients with MS was significantly different from that of non-MS subjects (p ˂ 0.001). Same was also observed when obese patients were compared with non-MS subjects. (p ˂ 0.001).  The prevalence of MS among Sudanese first-year university students in Khartoum is moderately high. Incidence of MS among the students is directly proportional to BMI.  Metabolic syndrome, Obesity, Hypertension, Diabetes, Dyslipidemia, Anthropometric

title: Impact of Ambulatory Blood Pressure Monitoring on Control of Untreated, Undertreated, and Resistant Hypertension in Older People in Spain.
abstract: The impact of ambulatory blood pressure monitoring (ABPM) on hypertension control has not been fully assessed across the treatment spectrum in older community-living individuals and could have important implications; specifically, the number of untreated, undertreated, and treatment-resistant uncontrolled hypertensives in need of or with unnecessary drug treatment could vary with respect to studies based on conventional blood pressure (BP) measured in clinical settings.



Cross-sectional study conducted in 2012 among 1118 community-living individuals aged ≥60 years in Spain.



Three conventional BP measurements at participants' homes and 24-hour ABPM were performed under standardized conditions. Uncontrolled hypertension (mean of the last 2 conventional BP readings ≥140/90 mm Hg) was considered undertreated if on 1 or 2 antihypertensive drugs, and apparently treatment-resistant if on ≥3 drugs. White-coat effect was defined as conventional BP ≥ 140/90 mm Hg and 24-hour BP <130/80 mm Hg.



Of 720 hypertensive patients (mean age, 72.3 ± 6.3 years; 51.3%, males), 64.4% had conventional BP ≥ 140/90 mm Hg, and from these 39.9% were untreated, 49.5% undertreated, and 10.6% apparently treatment-resistant. Among uncontrolled hypertensive patients, the white-coat effect was present in 52.4% of those untreated, in 53.5% of undertreated, and in 49% of apparent treatment-resistant. These white-coat results were similar or even higher across alternative BP thresholds.



One-half of older uncontrolled hypertensive patients studied at home were actually controlled according to ABPM, regardless of treatment status. This suggests reconsideration of treatment needs in these numerous white-coat hypertensive patients, who probably do not need drug treatment initiation or intensification.

title: Clinical evaluation of rosuvastatin in heart transplant patients with hypercholesterolemia and therapeutic failure of other statin regimens: short‐term and long‐term efficacy and safety results
abstract: We conducted an observational study of 30 heart transplant recipients with serum low‐density lipoprotein cholesterol (LDL‐c) >100 mg/dl despite previous statin therapy, who were treated with rosuvastatin 10 mg daily (5 mg in case of renal dysfunction). Serum lipids, creatine phosphokinase (CPK), bilirubin, and hepatic enzymes were prospectively measured 2, 4, and 12 weeks after the initiation of the drug. Clinical outcomes of patients who continued on long‐term rosuvastatin therapy beyond this 12‐week period were reviewed in February 2015. Over the 12‐week period following rosuvastatin initiation, serum levels of total cholesterol (TC) and LDL‐c and the ratio TC/high‐density lipoprotein cholesterol (HDL‐c) decreased steadily (P < 0.001). Average absolute reductions of these three parameters were –48.7 mg/dl, –46.6 mg/dl, and –0.9, respectively. Seventeen (57%) achieved a serum LDL‐c < 100 mg/dl. No significant changes from baseline were observed in serum levels of triglycerides, HDL‐c, hepatic enzymes, bilirubin, or CPK. Twenty‐seven (90%) patients continued on long‐term therapy with rosuvastatin over a median period of 3.6 years, with no further significant variation in lipid profile. The drug was suspended due to liver toxicity in 1 (3.3%) patient and due to muscle toxicity in 2 (6.7%) patients. All adverse reactions resolved rapidly after rosuvastatin withdrawal. Our study supports rosuvastatin as a reasonable alternative for heart transplant recipients with hypercholesterolemia and therapeutic failure of other statin regimens.

title: [Association of hyperuricemia with hyperlipidemia and obesity].
abstract: Various epidemiological evidences have shown the increased incidence of hyperuricemia in the subjects with hyperlipidemia and/or obesity. Our clinical study indicated the association was more close in hypertriglyceridemia to hyperuricemia than in hypercholesterolemia. Serum uric acid level increased more in Type IIb with elevated lipoprotein lipase (LPL) than those with low or normal LPL. Elevated LPL may be involved in the retarded uric acid clearance due to increased free fatty acids (FFA) in the serum, resulting in the elevation of uric acid and may be linked to the obesity-insulin resistance syndrome. Increased FFA may play an important role on the association of hyperuricemia with hypertriglyceridemia.

title: Relationship between Hyperuricemia and Lipid Profiles in US Adults
abstract: Although the link between hyperuricemia and metabolic syndrome had been recognized, the association of the dyslipidemia among individuals with hyperuricemia remains not comprehensively assessed.  Using NHANES III study, we examined the relation between serum lipid profiles and different serum uric acid levels, including serum total cholesterol, LDL cholesterol, triglycerides, HDL cholesterol, apolipoprotein-B, lipoprotein (a), apolipoprotein AI, ratio of triglycerides to HDL cholesterol, and ratio of apolipoprotein-B to AI.  After adjusting for potential confounders, average differences (95% confidence interval) comparing the top to the bottom (reference) serum uric acid were 0.29 (0.19, 0.39) mmol/L for total cholesterol, 0.33 (0.26, 0.41) mmol/L for triglycerides, 0.14 (0.01, 0.27) mmol/L for LDL cholesterol, −0.08 (−0.11, −0.05) mmol/L for HDL, and 0.09 (0.05, 0.12) g/L for serum apolipoprotein-B. Notably, ratios of triglycerides to HDL cholesterol and apolipoprotein-B to AI were also linearly associated with uric acid levels (P for trend < 0.001).  This study suggested that serum LDL cholesterol, triglycerides, total cholesterol, apolipoprotein-B levels, ratio of triglycerides to HDL cholesterol, and ratio of apolipoprotein-B to AI are strongly associated with serum uric acid levels, whereas serum HDL cholesterol levels are significantly inversely associated. In the clinical practice, the more comprehensive strategic management to deal with dyslipidemia and hyperuricemia deserves further investigation.

title: Polymorphisms of the Peroxisome Proliferator-Activated Receptor-γ (rs1801282) and its coactivator-1 (rs8192673) are associated with obesity indexes in subjects with type 2 diabetes mellitus
abstract: AbstractᅟThe aim of this study was to clarify whether common single nucleotide polymorphisms (SNPs) of the Peroxisome Proliferator-Activated Receptor-γ (PPAR-γ) gene (rs1801282) and the Peroxisome Proliferator-Activated Receptor-γ Coactivator-1 (PGC-1α) gene (rs8192673) are associated with obesity indexes (BMI, waist circumference) in subjects with type 2 diabetes mellitus (T2DM) in Caucasian population. The second aim was to find an association of both polymorphisms with T2DM.MethodsTwo exonic SNPs of both genes rs1801282 of the PPAR-γ gene and rs8192673 of the PGC-1α gene) were genotyped in 881 unrelated Slovene subjects (Caucasians) with T2DM and in 348 subjects without T2DM (control subjects).ResultsFemale homozygotes with the CC genotype of the rs8192673 had higher waist circumference in comparison with subjects with other genotypes. Homozygotes (females, males) with wild allele (Pro) of the rs1801282 (Pro12Ala polymorphism) had higher waist circumference in comparison with subjects with other genotypes. In the study, there were no differences in the distributions of the rs8192673 and the rs1801282 genotypes between patients with T2DM and controls. Linear regression analyses for both polymorphisms were performed and demonstrated an independent effect of the rs1801282 of the PPAR-γ on waist circumference in subjects with T2DM, whereas an independent effect on waist circumference was not demonstrated for the rs8192673 of the PGC-1α gene.ConclusionsIn a large sample of the Caucasians the rs8192673 of the PGC-1α gene and the rs1801282 of the PPAR-γ gene were associated with waist circumference in subjects with T2DM.