Serum uric acid, diuretic treatment and risk of cardiovascular events in the Systolic Hypertension in the Elderly Program (SHEP)

OBJECTIVE: To assess longitudinally the association of serum uric acid and its change due to diuretic treatment with cardiovascular events in hypertensive patients. DESIGN: Cohort study in a randomized trial. SETTING: Cohort of hypertensive patients. PARTICIPANTS: A total of 4327 men and women, aged > or = 60 years, with isolated systolic hypertension, randomized to placebo or chlorthalidone, with the addition of atenolol or reserpine if needed, were observed for 5 years. MAIN OUTCOME MEASURES: Major cardiovascular events, coronary events, stroke and all-cause mortality. RESULTS: Cardiovascular event rates for quartiles of baseline serum uric acid were: I, 32.7 per 1000 person-years; II, 34.5 per 1000 person-years; III, 38.1 per 1000 person-years; and IV, 41.4 per 1000 person-years (P for trend = 0.02). The adjusted hazard ratio (HR), of cardiovascular events for the highest quartile of serum uric acid versus the lowest quartile was 1.32 (95% CI, 1.03-1.69). The benefit of active treatment was not affected by baseline serum uric acid. After randomization, an increase of serum uric acid < 0.06 mmol/l (median change) in the active treatment group was associated with a HR of 0.58 (0.37-0.92) for coronary events compared with those with a serum uric acid increase > or = 0.06 mmol/l. This difference was not explained by blood pressure effects. Those with a serum uric acid increase > or = 0.06 mmol/l in the active treatment group had a similar risk of coronary events as the placebo group. CONCLUSIONS: Serum uric acid independently predicts cardiovascular events in older persons with isolated systolic hypertension. Monitoring serum uric acid change during diuretic treatment may help to identify patients who will most benefit from treatment.     

Uric acid is not an independent predictor of cardiovascular mortality in type 2 diabetes: a population-based study

ObjectiveAlthough some studies have suggested that uric acid is a risk factor for mortality, this relationship is still uncertain in people with type 2 diabetes.MethodsThe study base was the population-based cohort of 1540 diabetic subjects (median age 68.9 years) of the Casale Monferrato Study. The role of serum uric acid on 15-years all-cause, cardiovascular and non-cardiovascular mortality was assessed by multivariate Cox proportional hazards modeling.ResultsBaseline levels of serum uric acid were negatively correlated with HbA1c, were higher in men and in the elderly and were independently associated with components of the metabolic syndrome. Out of 14,179 person-years, 1000 deaths (514 due to cardiovascular diseases) were observed. Compared to the lower quartile of uric acid, HRs (95% CI) in the upper quartile were 1.47 (1.22–1.76) for all-cause mortality; 1.40 (1.09–1.80) for cardiovascular mortality and 1.50 (1.15–1.96) for non-cardiovascular mortality. In multiple adjusted models, however, HRs were 1.30 (1.06–1.60) for all-cause mortality, 1.13 (0.85–1.50) for cardiovascular mortality and 1.50 (1.11–2.02) for non-cardiovascular mortality (men 1.87, 1.19–2.95; women 1.20, 0.80–1.80); the latter appeared to be due to neoplastic diseases (HR in all combined quartiles vs. lower quartile: both sexes 1.59, 1.05–2.40; men 1.54, 0.83–2.84, women 1.68, 0.95–2.92).ConclusionsIn diabetic people, uric acid is associated with components of the metabolic syndrome but it may not be accounted as an independent risk factor for cardiovascular mortality. The increased all-cause mortality risk with higher levels of uric acid might be due to increased neoplastic mortality and deserves future studies.     

Long-term predictors of survival for the Seven Countries Study cohort from Crete: from 1960 to 2000

BACKGROUND: In 1960, all male inhabitants of a series of villages in rural Crete, born between 1900 and 1919, were invited to participate in the Seven Countries Study. Analysis of 25-year mortality data from the 16 cohorts of participants indicated that the cohort from Crete had the lowest age-standardised all-cause and coronary heart disease death rates. METHODS: At baseline, 686 Cretan men (98% of those invited) participated in health examinations. Mortality data were collected over 40 years. Time-fixed and updated covariate survival analysis techniques were applied to assess eight cardiovascular disease risk factors as long-term predictors of all-cause and cardiovascular disease mortality. RESULTS: The median survival time was 32 years. All-cause and cardiovascular mortality rates were 26 and 11 per 1000 person-years, respectively. Age (relative risk 1.11, 95% CI 1.09-1.13), diastolic blood pressure (relative risk 1.02, 95% CI 1.01-1.03), and smoking (relative risk 1.37, 95% CI 1.14-1.64) were positively associated and forced expiratory volume (relative risk 0.50, 95% CI 0.36-0.68) was negatively associated with all-cause mortality. Age (relative risk 1.13, 95% CI 1.09-1.16), diastolic blood pressure (relative risk 1.01, 95% CI 1.001-1.03), and forced expiratory volume (relative risk 0.53, 95% CI 0.32-0.89) were independent predictors of cardiovascular mortality. Serum cholesterol concentration and body mass index were not independently associated with death risk. CONCLUSIONS: The Cretan cohort displays favourable 40-year survival. Even so, long-term predictors of the hazard of both all-cause and cardiovascular disease mortality are present.     

Serum uric acid is associated with microalbuminuria in prehypertension

Serum uric acid is associated with cardiovascular disease. However, the independent role of uric acid in the development of cardiovascular disease is uncertain. This study examined the cross-sectional association of serum uric acid level with microalbuminuria among 6771 subjects without diabetes or hypertension. Blood pressure was categorized as prehypertension (systolic blood pressure, 120 to 140 mm Hg or diastolic blood pressure, 80 to 90 mm Hg) and normotension (systolic blood pressure, <120 mm Hg and diastolic blood pressure, <80 mm Hg). Microalbuminuria was found in 4.0% of normotensive subjects (n=4819) and in 7.9% of prehypertensive subjects (n=1952). Prehypertensive subjects with microalbuminuria had higher uric acid level than those with normoalbuminuria (men, 387 [68] mmol/L versus 371 [69] mmol/L; P=0.017; women 286 [56] mmol/L versus 262 [54] mmol/L; P=0.006). However, the difference in serum uric acid level according to the presence or absence of microalbuminuria was not found in the normotensive group. Multiple logistic regression models showed that, in the prehypertensive group, after adjustment for other cardiovascular risk factors, the highest uric acid quartile entailed >2 times greater risk for microalbuminuria than the lowest quartile in both men (odds ratio, 2.12; 95% CI, 1.16 to 3.87) and women (odds ratio, 3.36; 95% CI, 1.17 to 9.69). In the normotensive group, serum uric acid quartile did not show the independent association with microalbuminuria. In conclusion, serum uric acid level was strongly associated with microalbuminuria in prehypertensive subjects.     

Prognostic significance of serum creatinine and uric acid in older Chinese patients with isolated systolic hypertension

We examined the relation of serum creatinine and uric acid to mortality and cardiovascular disease in older (aged >/=60 years) Chinese patients with isolated systolic hypertension (systolic/diastolic blood pressure >/=160/<95 mm Hg). We used Cox regression to correlate outcome with baseline serum creatinine and uric acid measured in 1880 and 1873, respectively, of the 2394 patients enrolled in the placebo-controlled Systolic Hypertension in China (Syst-China) TRIAL: Median follow-up was 3 years. In multiple Cox regression analysis with adjustment for gender, age, active treatment, and other significant covariates, serum creatinine was significantly associated with a worse prognosis. The relative hazard rates (95% CIs) associated with a 20-micromol/L increase in serum creatinine for all-cause, cardiovascular, and stroke mortality were 1.16 (1.05 to 1.27, P=0.003), 1.15 (1.01 to 1.31, P=0.03), and 1.37 (1.13 to 1.65, P=0.001), respectively. In a similar analysis, which also accounted for serum creatinine, serum uric acid was also significantly and independently associated with excess mortality of cardiovascular disease and stroke. The relative hazard rates associated with a 50-micromol/L increase of serum uric acid were 1.14 (1.02 to 1.27, P=0.02) for cardiovascular mortality and 1.34 (1.14 to 1.57, P<0.001) for fatal stroke. In conclusion, in older Chinese patients with isolated systolic hypertension, serum creatinine and serum uric acid were predictors of mortality.     

Survival impact of serum uric acid levels in children and adolescents

Evidence is limited on the association between hyperuricaemia and mortality in children and adolescents. This study was to investigate this association in the paediatric population. The study included children and adolescents who had undergone serum uric acid (SUA) measurement at the Chang Gung Memorial Hospital between 1997 and 2008. The survival status and cause of death of the included were ascertained by examining the National Death Registry of Taiwan. Hyperuricaemia was defined as a SUA level greater than 7.0 mg/dL. We included 13,241 patients (male, n = 7,454; female, n = 5,787) of mean age 14.3 ± 4.9 years. During the 82,800 person-years of follow-up, 455 deaths were identified, which corresponded to a crude mortality rate of 5.50 deaths per 1,000 person-years. Compared with individuals with a SUA <6.0 mg/dL, those with a SUA of 6.0–8.9, 9.0–11.9 and ≥12 mg/dL had an age- and sex-adjusted HR (95 % CI) of 1.02 (0.82–1.26), 1.48 (1.08–2.02) and 4.73 (2.67–8.37). After adjustment for age, sex and history of diabetes mellitus and hypertension, hyperuricaemia was found to be associated with a HR (95 % CI) of 1.38 (1.13–1.69; p < 0.001) for all-cause mortality. Hyperuricaemia was associated with an increased risk of mortality due to cardiovascular diseases (HR, 5.0; 95 % CI 1.79–13.94; p = 0.001) and kidney diseases (11.71; 3.13–43.78; p < 0.001). Paediatric patients with hyperuricaemia were at increased risk of mortality, especially due to kidney and cardiovascular diseases.     

Distribution of Serum Uric Acid in Black Africans and Its Association With Cardiovascular Risk Factors

Hyperuricemia is associated with cardiovascular disease and its prevalence is unknown in black Africans. This study reports hyperuricemia distribution and its association with cardiovascular risk factors in a selected Angolan population. A cross‐sectional study in 585 black Africans was performed. Hyperuricemia was defined as uric acid >7.0 mg/dL in men or >5.7 mg/dL in women. Overall prevalence was 25%. Hyperuricemia was associated with hypertension (odds ratio [OR], 2.20; confidence interval [CI], 95% 1.41–3.47), high waist circumference (OR, 1.67; CI, 95% 1.05–2.65), and metabolic syndrome (OR, 1.66; CI, 95% 1.07–2.57). Compared to those with uric acid levels in the first quartile, individuals in the fourth quartile showed higher body mass index, waist circumference, systolic blood pressure, and plasma levels of creatinine and triglycerides. Hypertension, high waist circumference, and metabolic syndrome were the major cardiovascular risk factors associated with hyperuricemia.     

Serum uric acid level and all-cause and cardiovascular mortality in Chinese elderly: A community-based cohort study in Shanghai

Background and aimsThe association between serum uric acid (SUA) and the all-cause and cardiovascular diseases (CVD) mortality remains controversial, but few studies based on the community population in Shanghai have been reported. We aimed to evaluate the association of SUA level with all-cause and CVD mortality in Chinese elderly based on a community-based cohort study in Shanghai of China.Methods and resultsA total of 12,071 eligible participants were included, with a cumulative follow-up period of 46,063.65 person-years and a median of 4.67 years. The time-dependent Cox regression model indicated that when SUA level was classified into quartile groups, no significant association was observed between SUA level and all-cause death in both men and women and between SUA level and CVD mortality in men. However, the HR (95%CI) between SUA groups and CVD death in women was 3.75 (1.49–9.43) for quartile 1, 3.66 (1.53–8.76) for quartile 2, and 2.98 (1.33–6.69) for quartile 4, respectively, when compared with the quartile 3 SUA level. A significant non-linear association was observed between SUA level and CVD death in elderly women. An increased risk of CVD death was observed among women with SUA level less than 4.30 mg/dL at the baseline, and a lower risk, among women with SUA level of 4.30–4.72 mg/dL at the baseline.ConclusionThe non-linear association between SUA level and CVD mortality in elderly women suggests a potential benefit of controlling SUA level at4.30–4.72 mg/dL in elderly Chinese women.     

Uric acid level and elevated blood pressure in US adolescents: National Health and Nutrition Examination Survey, 1999-2006

Uric acid is associated with cardiovascular disease and cardiovascular disease risk factors in adults, including chronic kidney disease, coronary artery disease, stroke, diabetes mellitus, preeclampsia, and hypertension. We examined the association between uric acid and elevated blood pressure in a large, nationally representative cohort of US adolescents, a population with a relatively low prevalence of cardiovascular disease and cardiovascular disease risk factors. Among 6036 adolescents 12 to 17 years of age examined in the 1999-2006 National Health and Nutrition Examination Survey, the mean age was 14.5 years, 17% were obese (body mass index: ≥95th percentile), and 3.3% had elevated blood pressure. Mean serum uric acid level was 5.0 mg/dL, and 34% had a uric acid level ≥5.5 mg/dL. In analyses adjusted for age, sex, race/ethnicity, and body mass index percentile, the odds ratio of elevated blood pressure, defined as a systolic or diastolic blood pressure ≥95th percentile for age, sex, and height, for each 0.1-mg/dL increase in uric acid level was 1.38 (95% CI: 1.16-1.65). Compared with <5.5 mg/dL, participants with a uric acid level ≥5.5 mg/dL had a 2.03 times higher odds of having elevated blood pressure (95% CI: 1.38-3.00). In conclusion, increasing levels of serum uric acid are associated with elevated blood pressure in healthy US adolescents. Additional prospective studies and clinical trials are needed to determine whether uric acid is merely a marker in a complex metabolic pathway or causal of hypertension and, thus, a potential screening and therapeutic target.     

Association between Serum Inorganic Phosphorus Levels and Adverse Outcomes in Chronic Kidney Disease: The Fukushima CKD Cohort Study

Objective Although an association between serum inorganic phosphorus levels and a poor prognosis has been noted in dialysis patients, these associations have been insufficiently reported in non-dialysis-dependent chronic kidney disease (NDD-CKD) patients. This study attempted to determine the association between serum inorganic phosphorus levels and adverse outcomes in Japanese NDD-CKD patients. Methods We investigated the relationships between serum inorganic phosphorus levels and adverse outcomes, such as kidney events, cardiovascular events, and all-cause death, in Japanese NDD-CKD patients using longitudinal data from the Fukushima CKD Cohort Study with a median follow-up period of 2.8 years. The study evaluated 822 patients with NDD-CKD enrolled between June 2012 and July 2014. A kidney event was defined as a combination of doubling of the baseline serum creatinine or end-stage renal disease. Cox regression was performed to analyze the relationships of the quartile of the serum inorganic phosphorus with kidney events, cardiovascular events, and all-cause death. Results The frequency of kidney events per 1,000 person-years exhibited a U-shaped distribution based on serum inorganic phosphorus levels, with these levels not significantly associated with an increased risk of cardiovascular events and all-cause death. A multivariable Cox regression analysis showed an increased risk of kidney events for the highest quartile of the serum inorganic phosphorus levels (≥3.7 mg/dL) versus the second quartile (2.9-3.2 mg/dL, hazard ratio, 3.30; 95% confidence interval, 1.50-7.28; p=0.003). There were no significant associations between the serum calcium levels and adverse outcomes. Conclusion Serum inorganic phosphorus levels were associated with an increased risk of CKD progression in Japanese NDD-CKD patients.     

Hyperuricemia and coronary heart disease: A systematic review and meta‐analysis

Objective

The role of serum uric acid as an independent risk factor for cardiovascular disease remains unclear, although hyperuricemia is associated with cardiovascular disease such as coronary heart disease (CHD), stroke, and hypertension.

Methods

A systematic review and meta‐analysis using a random‐effects model was conducted to determine the risk of CHD associated with hyperuricemia in adults. Studies of hyperuricemia and CHD were identified by searching major electronic databases using the medical subject headings and keywords without language restriction (through February 2009). Only prospective cohort studies were included if they had data on CHD incidences or mortalities related to serum uric acid levels in adults.

Results

Twenty‐six eligible studies of 402,997 adults were identified. Hyperuricemia was associated with an increased risk of CHD incidence (unadjusted risk ratio [RR] 1.34, 95% confidence interval [95% CI] 1.19–1.49) and mortality (unadjusted RR 1.46, 95% CI 1.20–1.73). When adjusted for potential confounding, the pooled RR was 1.09 (95% CI 1.03–1.16) for CHD incidence and 1.16 (95% CI 1.01–1.30) for CHD mortality. For each increase of 1 mg/dl in uric acid level, the pooled multivariate RR for CHD mortality was 1.12 (95% CI 1.05–1.19). Subgroup analyses showed no significant association between hyperuricemia and CHD incidence/mortality in men, but an increased risk for CHD mortality in women (RR 1.67, 95% CI 1.30–2.04).

Conclusion

Hyperuricemia may marginally increase the risk of CHD events, independently of traditional CHD risk factors. A more pronounced increased risk for CHD mortality in women should be investigated in future research.     

Serum uric acid concentration as a risk factor for cardiovascular mortality: a longterm cohort study of atomic bomb survivors

OBJECTIVE: To elucidate the association of serum uric acid concentration with cardiovascular mortality risk. METHODS: Serum uric acid level measured from 1966 through 1970 in 10,615 Japanese individuals from a cohort of atomic bomb survivors was analyzed for association with subsequent cardiovascular and all-cause mortality until 1999 using the Cox proportional hazard model. RESULTS: During an average followup of 24.9 years, 5225 deaths occurred, of which 1984 were ascribed to cardiovascular disease. In men, after adjustment for age, elevated serum uric acid level was associated with both cardiovascular and all-cause mortality. After additional adjustment for potential cardiovascular disease risk factors including body mass index, smoking status, alcohol consumption, systolic blood pressure, cholesterol level, and histories of hypertension, diabetes and cardiovascular disease, elevated serum uric acid level in men was associated with all-cause mortality but not with cardiovascular mortality. In women, even after these adjustments, elevated serum uric acid level was significantly associated with cardiovascular and all-cause mortality. CONCLUSION: Increased serum uric acid level is a significant and independent risk factor for cardiovascular mortality in women and for all-cause mortality in both men and women.     

Prognostic usefulness of free fatty acids in patients with stable coronary heart disease

Circulating nonesterified or free fatty acids (FFAs) may contribute to the development of cardiovascular pathology and correlate with ischemia in acute cardiovascular conditions. The aim of this study was to assess whether serum levels of FFAs are associated with long-term prognosis in subjects with stable coronary heart disease. This observational prospective cohort study included 1,206 participants in 3-weeks inpatient rehabilitation programs after acute myocardial infarction, coronary syndromes, or coronary intervention at 2 rehabilitation clinics in Germany (1999 to 2000). Eight-year prognosis (time to a secondary fatal or nonfatal cardiovascular disease event including myocardial infarction and stroke [n = 153] and time to death from any cause [n = 124]) was examined according to FFA quartiles and in spline regression. FFAs were correlated with established serum markers of cardiovascular risk and strongly related to secondary cardiovascular events and all-cause mortality in age- and gender-adjusted analysis. When additionally controlling for multiple established risk factors and risk markers, the hazard ratio in the fourth versus first quartile was 1.34 (95% confidence interval 0.79 to 2.24) for secondary cardiovascular events and 1.09 (95% confidence interval 0.62 to 1.91) for all-cause mortality. Dose-response modeling suggested that very high FFAs might predict an increased risk for mortality (hazard ratio 1.98, 95% confidence interval 0.98 to 4.02, for 95th percentile vs first quartile). In conclusion, FFAs are closely correlated with cardiovascular risk markers, and in particular, very high FFA might identify patients with stable coronary heart disease with worse prognoses.     

Serum uric acid and risk of death from cancer, cardiovascular disease or all causes in men.

OBJECTIVE: Although many epidemiological studies have suggested that increased serum uric acid levels are a risk factor for mortality, this relationship remains uncertain. This cohort study examined the effects of serum uric acid level on death from cancer, atherosclerotic cardiovascular disease (ASCVD) or all causes in men. METHOD: A 9-year, prospective cohort study was carried out with 22698 Korean men, aged 30 to 77 years, who received health insurance from the National Health Insurance Corporation and who underwent biennial, secondary medical evaluations in 1992-1996. The main outcome measures were death from cancer, ASCVD or all causes, compared by quintiles of serum uric acid level. At baseline, the mean (SD) level of serum uric acid was 354.4 (98.1) micromol/l. RESULTS: During 199746 person-years of follow-up, there were 387 cancer deaths, 323 ASCVD (99 ischaemic heart disease, 192 stroke) deaths and 1625 all-cause deaths. In multivariate Cox proportional hazards models, having controlled for age, current smoking, diabetes, hypertension and hypercholesterolaemia, uric acid levels were not associated with mortality from cancer, ASCVD or all causes. However, for those with diabetes, uric acid levels were associated with mortality from all causes even after full adjustment of the covariates. When the interaction term was included in the multivariate model, there was significant interactive effect of uric acid with diabetes (RR=1.26, 95% confidence interval 1.02-1.55) on the risk of all cause of death, whereas the effects of uric acid itself did not attain significance. CONCLUSION: These findings indicate that uric acid level is not an independent risk factor for death from cancer, ASCVD or all causes.     

Relation of serum vitamin A levels to all-cause and cause-specific mortality among older adults in the NHANES III population

AimsAlthough studies have suggested that vitamin A is associated with cardiovascular events and mortality, it remains unclear whether low doses or high doses of vitamin A have harmful effects on the cardiovascular system. This study investigated whether serum vitamin A levels are associated with all-cause and cause-specific mortality in US older adults.Data synthesisWe analyzed the mortality information for 6069 participants aged 50 years or older who had serum vitamin A data available from the baseline examination. The participants were categorized as having deficient (<30 μg/dL), normal (30–80 μg/dL), or excessive (>80 μg/dL) levels of serum vitamin A, and a multivariate Cox proportional hazards regression analysis was performed on mortality. We found a U-shaped association between serum vitamin A levels and death from all-cause and cause-specific mortality among US adults. Comparing the normal range of serum vitamin A, the hazard ratio with deficient serum vitamin A was 2.9 (95% CI 2.0–4.3) for all-cause mortality, 2.1 (95% CI 1.1–4.1) for cardiovascular-related mortality and 2.5 (95% CI 1.2–5.3) for coronary artery disease-related mortality. Excessive serum vitamin A was associated with a 1.2-fold (95% CI 1.1–1.4) increased risk of all-cause mortality, a 1.4-fold (95% CI 1.2–1.8) increased risk of cardiovascular-related mortality, and a 1.5-fold (95% CI 1.2–2.0) increased risk of coronary artery disease-related mortality compared with the reference group.ConclusionThe finding suggests that serum vitamin A levels less than 30 μg/dL or greater than 80 μg/dL levels may indicate a high risk of subsequent mortality.     

Cardiovascular outcomes in framingham participants with diabetes: the importance of blood pressure

We designed this study to explore to what extent the excess risk of cardiovascular events in diabetic individuals is attributable to hypertension. We retrospectively analyzed prospectively collected data from the Framingham original and offspring cohorts. Of the 1145 Framingham subjects newly diagnosed with diabetes mellitus who did not have a previous history of cardiovascular events, 663 (58%) had hypertension at the time that diabetes mellitus was diagnosed. During 4154 person-years of follow-up, 125 died, and 204 experienced a cardiovascular event. Framingham participants with hypertension at the time of diabetes mellitus diagnosis exhibited higher rates of all-cause mortality (32 versus 20 per 1000 person-years; P<0.001) and cardiovascular events (52 versus 31 per 1000 person-years; P<0.001) compared with normotensive subjects with diabetes mellitus. After adjustment for demographic and clinical covariates, hypertension was associated with a 72% increase in the risk of all-cause death and a 57% increase in the risk of any cardiovascular event in individuals with diabetes mellitus. The population-attributable risk from hypertension in individuals with diabetes mellitus was 30% for all-cause death and 25% for any cardiovascular event (increasing to 44% and 41%, respectively, if the 110 normotensive subjects who developed hypertension during follow-up were excluded from the analysis). In comparison, after adjustment for concurrent hypertension, the population-attributable risk from diabetes mellitus in Framingham subjects was 7% for all-cause mortality and 9% for any cardiovascular disease event. Although diabetes mellitus is associated with increased risks of death and cardiovascular events in Framingham subjects, much of this excess risk is attributable to coexistent hypertension.     

Associations of vitamin B6 turnover rate with the risk of cardiovascular and all-cause mortality in hypertensive adults

Background and aimThis study was to assess the association between vitamin B6 turnover rate and mortality in hypertensive adults.Methods and resultsVitamin B6 status including serum pyridoxal-5′-phosphate (PLP) levels, serum 4-pyridoxal acid (4-PA) levels, and vitamin B6 turnover rate (4-PA/PLP) were obtained from the 2005–2010 National Health and Nutrition Examination Survey (NHANES) dataset of hypertensive adults with follow-up through December 30, 2019. Using Cox proportional risk regression models, Hazard ratios (HRs) and 95% confidence intervals (CIs) were analyzed for PLP, 4-PA and 4-PA/PLP quartiles in relation to cardiovascular and all-cause mortality. A total of 5434 participants were included in this study (mean age, 58.48 years; 50.4% men), and the median 4-PA/PLP was 0.75. The median follow-up time was 11.0 years, with 375 and 1387 cardiovascular and all-cause deaths, respectively. In multivariate COX regression models, PLP was negatively associated with cardiovascular mortality (HR [95% CI] quartile 4 vs. 1: 0.66 [0.47–0.94], P_trend = 0.03) and 4-PA/PLP was positively associated with cardiovascular mortality (HR [95% CI] quartile 4 vs.1: 1.80 [1.21–2.67], P_trend = 0.01). Similarly, the higher the quartile of PLP, the lower the risk of all-cause mortality (HR [95% CI] quartile 4 vs. 1: 0.67 [0.56–0.80], P_trend < 0.01). The higher the quartile of 4-PA and 4-PA/PLP, the higher the risk of all-cause mortality (HR [95% CI] quartile 4 vs. 1: 1.22 [1.01–1.48], P_trend < 0.01; and 2.09 [1.71–2.55], P_trend < 0.01).ConclusionThe findings suggested that higher vitamin B6 turnover rate was associated with an increased risk of cardiovascular and all-cause mortality in hypertensive adults.     

Uric Acid Levels and All-Cause and Cardiovascular Mortality in the Hemodialysis Population

Summary

Background and objectives

Hyperuricemia is associated with hypertension, coronary artery disease, and chronic kidney disease. However, there are no specific data on the relationship of uric acid to cardiovascular disease in the chronic hemodialysis setting.

Design, setting, participants, & measurements

Data from 5827 patients on chronic hemodialysis from six countries affiliated with the Dialysis Outcomes and Practice Patterns Study (DOPPS) were analyzed. All laboratory data were based upon the initial cross-section of patients in DOPPS I and II. Cox regression was used to calculate the hazard ratio (HR) of all-cause and cardiovascular (CV) mortality with adjustments for case-mix including 14 classes of comorbidity.

Results

There were no clinically significant differences in baseline characteristics between those who had measured uric acid (n = 4637) and those who did not (n = 1190). Uric acid level was associated with lower all-cause mortality (HR: 0.95, 95% confidence interval [CI]: 0.90 to 1.00 per 1 mg/dl higher uric acid level) and CV mortality (HR: 0.92, 95% CI: 0.86 to 0.99). When analyzed as a dichotomous variable, the adjusted HR at uric acid ≤8.2 mg/dl compared with >8.2 mg/dl was 1.24 (95% CI: 1.03 to 1.49) for all-cause mortality and 1.54 (95% CI: 1.15 to 2.07) for CV mortality.

Conclusions

Higher uric acid levels were associated with lower risk of all-cause and CV mortality in the hemodialysis population. These results are in contrast to the association of hyperuricemia with higher cardiovascular risk in the general population and should be the subject of further research.     

Efficacy of treating hypertension in women

OBJECTIVE: To assess whether the relative and absolute benefit of hypertension treatment in women varies with age or race. DESIGN: Systematic review of studies from 1966 to 1998 using MEDLINE, reviews, and consultation with experts. Eleven randomized controlled trials of pharmacologic treatment of prJgiary hypertension with cardiovascular morbidity and mortality outcomes were selected, with a pooled population of 23,000 women. Relative risks were combined for each end point to form a summary risk ratio using meta-analytic techniques based on a random-effects model. Summary risk ratios were converted to numbers needed to treat (NNTs). Data were dichotomized by age to approxJgiate menopausal status (30 to 54 years, and 55 years and older), and by race (white and African American). MAIN RESULTS: In women aged 55 years or older (90% white), hypertension treatment resulted in a 38% risk reduction in fatal and nonfatal cerebrovascular events (95% confidence interval [CI] 27%, 47%; 5-year NNT 78), a 25% reduction in fatal and nonfatal cardiovascular events (95% CI 17%, 33%; 5-year NNT 58), and a 17% reduction in cardiovascular mortality (95% CI 3%, 29%; 5-year NNT 282). In women aged 30 to 54 years (79% white), hypertension treatment resulted in a 41% risk reduction in fatal and nonfatal cerebrovascular events (95% CI 8%, 63%; 5-year NNT 264), and a 27% risk reduction in fatal and nonfatal cardiovascular events (95% CI 4%, 44%; 5-year NNT 259). Hypertension treatment in African-American women (mean age, 52 years) reduced the risk of fatal and nonfatal cerebrovascular events by 53% (95% CI 29%, 69%; 5-year NNT 39), fatal and nonfatal cardiovascular events by 45% (95% CI 18%, 63%; 5-year NNT 21), fatal and nonfatal coronary events by 33% (95% CI 6%, 52%; 5-year NNT 48), and all-cause mortality by 34% (95% CI 14%, 49%; 5-year NNT 32). Analyses in white women aged 30 to 54 years did not show any statistically significant treatment benefit or harm. CONCLUSIONS: Hypertension treatment lowers the relative and absolute risk of cardiovascular morbidity and mortality in women aged 55 years and older and in African-American women of all ages. A greater effort should be made to increase awareness and treatment in these groups of women. Although relative risk reductions for cerebrovascular and cardiovascular events are sJgiilar for younger and older women, the NNT of younger women is at least 4 tJgies higher. Decisions about treatment of hypertension in younger white women should be influenced by the individual patient's absolute risk of cardiovascular disease.     

Serum uric acid and its change with the risk of type 2 diabetes: A prospective study in China

ObjectiveTo assess the association of baseline uric acid levels and their changes from baseline to Year 1 with the risk of type 2 diabetes.Research design and methodsThis study cohort included 9471 subjects without a history of diabetes at baseline. The incident diabetes was diagnosed according to the American Diabetes Association standard.ResultsDuring a mean follow-up of 2.9 years, we identified 762 type 2 diabetes cases. Multivariate-adjusted hazard ratios (HRs) of diabetes across baseline tertiles of serum uric acid were 1.00, 1.15, and 1.32 (P for trend = 0.018), respectively. Participants with hyperuricemia compared with those without had a 1.20-fold (95% confidence interval [CI] 1.01−1.44) risk of diabetes. When uric acid was examined as a continuous variable, multivariable-adjusted HR of diabetes for each 1 mg/dL (60 μmol/L) increase in serum uric acid was 1.09 (95% CI 1.03−1.15). Compared with subjects with stable serum uric acid from baseline to Year 1 (±10%), those with uric acid gain ≥30% had a 30% (95% CI 1.01–1.79) increased risk of diabetes and those with uric acid loss ≥10% had a 21% (95% 0.62−0.99) decreased risk of diabetes. This positive association between baseline serum uric acid and diabetes risk was consistent among subjects younger and older than 45 years, non-obese and obese participants, and men.ConclusionsHigh level of baseline serum uric acid and serum uric acid gain from baseline to Year 1 are associated with an increased risk of type 2 diabetes among Chinese adults.