Background: Elevated serum uric acid (SUA) levels have been independently associated with cardiovascular disease. Stress myocardial perfusion positron emission tomography (PET) allows for measurement of absolute myocardial blood flow (MBF) and quantification of global left ventricular coronary flow reserve (CFR). A CFR <2.0 is considered impaired coronary vascular function, and it is associated with increased cardiovascular risk. We evaluated the relationship between SUA and PET-measured markers of coronary vascular function. Methods: We studied adults undergoing a stress myocardial perfusion PET on clinical grounds (1/2006-3/2014) who also had ≥1 SUA measurement within 180 days from the PET date. Multivariable linear regression estimated the association between SUA and PET-derived MBF and CFR. We also stratified analyses by diabetes status. Results: We included 382 patients with mean (SD) age of 68.4 (12.4) years and mean (SD) SUA level of 7.2 (2.6) mg/dl. 36% were female and 29% had gout. Median [IQR] CFR was reduced at 1.6 [1.2, 2.0] and median [IQR] stress MBF was 1.5 [1.1, 2.1] ml/min/g. In the adjusted analysis, SUA was inversely associated with stress MBF (β = -0.14, p = 0.01) but not with CFR. Among patients without diabetes (n = 215), SUA had a negative association with CFR (β = -0.15, p = 0.02) and stress MBF (β = -0.19, p = 0.01) adjusting for age, sex, extent of myocardial scar and ischemia, serum creatinine and gout. In diabetic patients (n = 167), SUA was not associated with either CFR or MBF. Conclusions: In this cross-sectional study, higher SUA is modestly associated with worse CFR and stress MBF among patients without diabetes.
Research Article; Medicine and health sciences; Endocrinology; Endocrine disorders; Diabetes mellitus; Metabolic disorders; Biology and life sciences; Anatomy; Body fluids; Blood; Blood flow; Physiology; Inflammatory diseases; Gout; Rheumatology; Vascular medicine; Coronary heart disease; Cardiology; Research and analysis methods; Imaging techniques; Neuroimaging; Positron emission tomography; Neuroscience; Diagnostic medicine; Diagnostic radiology; Tomography; Radiology and imaging; Biochemistry; Biomarkers; Creatinine; Physical sciences; Chemistry; Chemical compounds; Acids; Uric acid; Ischemia
A number of large epidemiologic studies have demonstrated an independent association between serum uric acid (SUA) levels and risk of myocardial infarction (MI), heart failure, stroke, and cardiovascular mortality.[[
Coronary flow reserve (CFR)—the ratio of peak hyperemic myocardial blood flow (MBF) over MBF at rest as measured by positron emission tomography (PET)–is a robust and reproducible clinical measure of the integrated hemodynamic effects of epicardial coronary artery stenoses, diffuse atherosclerosis, vessel remodeling, endothelial dysfunction, and microvascular dysfunction on myocardial tissue perfusion.[[
Over the past decades, the association between hyperuricemia and cardiovascular disease has been extensively studied. The association between SUA and increased cardiovascular risk appears to be only partially accounted by traditional coronary risk factors. This suggests that other mechanisms may contribute to the association between the SUA and increased cardiovascular risk. One such mechanism may involve the potential adverse effect of SUA on vascular function and in particular endothelial function, thereby increasing the potential for coronary vasoconstriction and thrombosis. To date, the direct effect of hyperuricemia on coronary vascular function, as assessed by CFR, has not been studied. We therefore conducted a cross-sectional study to evaluate coronary vascular function related to SUA levels in patients referred for stress myocardial perfusion PET. In addition, we examined whether the relationship between SUA levels and coronary vascular function differed by presence of diabetes based on the close relationship between hyperuricemia, gout and diabetes.[[
All patients clinically referred for stress myocardial perfusion PET at the Brigham and Women’s Hospital in Boston, Massachusetts, USA between January 2006 and March 2014 were eligible for inclusion. Of those, we selected patients with at least one SUA level measurement during the 180-day period before or after the PET test date. In patients with multiple PET tests during the study period, we included the study closest to the date of SUA level measurement. The study protocol was approved by the Institutional Review Board of the Brigham and Women’s Hospital which granted a waiver of informed consent.
SUA level measured by enzymatic colorimetric assay in 180 days before or after the PET test was the exposure of interest. Hyperuricemia was defined as ≥7 mg/dl in men and ≥6 mg/dl in women.
The primary outcomes of interest were stress MBF and CFR quantified using PET. Absolute MBF in milliliter/minute/gram (ml/min/g) was computed from the dynamic rest and stress imaging series with commercially available software (Corridor4DM; INVIA Medical Imaging Solution, Ann Arbor, MI) and previously validated methods.[[
Following standard imaging protocols, patients were studied with a whole-body PET/computed tomography scanner (Discovery RX or STE LightSpeed 64, GE Healthcare, Milwaukee, WI) after at least 4 hours of fasting. Patients refrained from caffeine- and methylxanthine-containing substances and drugs for 24 hours before their scans. Briefly, at rest, radionuclide imaging was obtained with an intravenous bolus administration of
We assessed a number of pre-defined variables potentially related to hyperuricemia or coronary vascular function based on patient interview and/or medical record data in the Partners Healthcare Research Patient Data Registry from the 180-day period immediately before or after the PET test date. These variables were: age and sex; body mass index; comorbidities including gout, hypertension, diabetes, smoking, coronary artery disease, heart failure, and dyslipidemia; medications including beta blockers, calcium channel blockers, nitrates, angiotensin-converting enzyme inhibitors, diuretics, gout-related medications (i.e., allopurinol, febuxostat and colchicine), and aspirin; and laboratory data including SUA, serum creatinine, LDL cholesterol and C-reactive protein levels.
Patient characteristics were compared between the hyperuricemia and normouricemia groups. Statistical significance was assessed with Wilcoxon rank sum tests or two-sided t-tests for continuous variables and Fisher’s exact or chi
We identified a total of 382 patients including 208 with hyperuricemia and 174 with normouricemia. Table 1 presents patient characteristics. Mean (SD) age was 68.4 (12.4) years and 36% were female. Mean (SD) SUA level was 7.2 (2.6) mg/dl and 29% had gout. Cardiovascular comorbidities were prevalent as 85% had hypertension, 27% CAD and 11% heart failure. Diabetes was present in 44%, and 23% had any use of allopurinol or febuxostat.
null: Study cohort characteristics.
N Overall Hyperuricemia Normouricemia p-value 382 208 174 Mean ± SD, median [IQR] or percentage Uric acid level, mg/dl 7.2 ± 2.67.0 [5.4, 8.7] 9.0 ± 2.18.5 [7.4, 10.1] 5.1 ± 1.25.3 [4.5, 6.0] <0.001 Age, years 68.4 ± 12.469.0 [60.0, 77.0] 68.9 ± 12.069.0 [60.0, 78.0] 67.8 ± 12.969.0 [60.0, 76.0] 0.398 Female 36 37 34 0.68 Body mass index, kg/m2 29.0 [25.0, 34.0] 29.0 [26.0, 36.0] 28.0 [24.0, 33.0] 0.08 Comorbidities Hypertension 85 91 78 0.001 Diabetes 44 50 37 0.012 Gout 29 39 18 <0.001 Smoking 6 6 7 0.641 Coronary artery disease 27 28 26 0.682 Heart failure 11 16 4 <0.001 Dyslipidemia 75 77 72 0.242 Serum creatinine, mg/dl a 1.2 [0.9, 1.9] 1.4 [1.1, 2.1] 1.0 [0.8, 1.4] <0.001 LDL level, mg/dl b 79.0 [58.0, 97.0] 79.0 [57.0, 97.0] 78.0 [61.0, 100.0] 0.721 Medications Beta blockers 69 71 66 0.318 Calcium channel blockers 26 32 20 0.008 Nitrates 19 24 13 0.008 ACE inhibitors 40 39 42 0.519 Diuretics 47 59 33 <0.001 Aspirin 66 67 65 0.6 Statins and other lipid lowering drugs 71 74 68 0.205 Colchicine 8 13 3 <0.001 Xanthine oxidase inhibitors 23 30 14 <0.001 Cardiac function Heart rate at rest, per minute 70.0 [63.0, 80.0] 71.0 [63.0, 79.5] 69.0 [62.0, 80.0] 0.312 Systolic blood pressure at rest, mmHg 142.0 [127.0, 162.0] 142.0 [127.0, 163.0] 142.0 [125.0, 161.0] 0.638 LVEF at rest, %c 53.0 [40.0, 62.0] 50.0 [35.0, 62.0] 56.0 [45.0, 63.0] 0.004 LVEF at stress, %d 57.0 [44.0, 67.0] 55.0 [39.0, 64.0] 61.0 [47.0, 70.0] 0.001 Sum stress score 4.0 [0.0, 14.0] 6.0 [0.0, 16.0] 2.0 [0.0, 11.0] 0.004 Sum difference score 1.0 [0.0, 6.0] 2.0 [0.0, 6.0] 0.0 [0.0, 5.0] 0.155 Sum rest score 0.0 [0.0, 6.0] 0.0 [0.0, 7.0] 0.0 [0.0, 3.0] 0.003 Myocardial blood flow at rest, mL/min/g 1.0 [0.8, 1.2] 0.9 [0.7, 1.2] 1.0 [0.8, 1.3] 0.055 Myocardial blood flow at stress, mL/min/g 1.5 [1.1, 2.1] 1.4 [1.0, 2.0] 1.6 [1.2, 2.3] 0.003 Coronary flow reserve 1.6 [1.2, 2.0] 1.5 [1.2, 1.9] 1.6 [1.2, 2.1] 0.04
- 5 SD: standard deviation, LDL: low density lipoprotein, ACE: angiotensin converting enzyme, LVEF: left ventricle ejection fraction
- 6 P-values are for the comparisons between hyperuricemia and normouricemia.
1 a Missing in <1% of the hyperuricemia group and 2% of the normouricemia group
- 2 b Missing in 20% of the hyperuricemia group and 22% of the normouricemia group
- 3 c Missing in 3% of the hyperuricemia group and 2% of the normouricemia group
- 4 d Missing in 2% of the hyperuricemia group and 6% of the normouricemia group
The mean (SD) uric acid level in milligram per deciliter was 9.0 (2.1) for the hyperuricemia group and 5.1 (1.2) for the normouricemia group. Hypertension, diabetes, heart failure, gout, and use of calcium channel blockers, nitrates, xanthine oxidase inhibitors, and diuretics were more common in patients with hyperuricemia. The patients with hyperuricemia had impaired renal function with median [IQR] serum creatinine of 1.4 [1.1, 2.1] mg/dl whereas the median [IQR] serum creatinine was normal in the normouricemia group (1.0, [0.8, 1.4]). Median LDL level was similar between the groups.
The median [IQR] summed stress score was 4 [0.0, 14] for the overall cohort, 6.0 [0.0, 16.0] for the hyperuricemia, and 2.0 [0.0, 11] for the normouricemia group, indicating more prevalent myocardial damage in patients with hyperuricemia. 185 patients (48.4%) in the overall cohort had a normal summed stress score ≤3. Median [IQR] CFR was 1.6 [1.2, 2.0] and median [IQR] stress MBF was 1.5 [1.1, 2.1] ml/min/g in the overall cohort. The median CFR and stress MBF were lower (worse) in the hyperuricemia group versus the normouricemia group. There were weak negative correlations between SUA and CFR (r = -0.13, p = 0.015) and between SUA and MBF at stress (r = -0.24, p<0.001) in the unadjusted analysis (see S1 and S2 Figs). At rest, the heart rate and systolic blood pressure were similar between the hyperuricemia and normouricemia groups, but left ventricular ejection fraction was lower in patients with hyperuricemia (Table 1).
Table 2 presents the main results from the multivariable linear regression models. In the final multivariable linear regression model adjusting for age, sex, diabetes, summed stress score, serum creatinine and gout, SUA was associated with stress MBF (β = -0.14, p = 0.01), but not with CFR (β = -0.07, p = 0.14). In a sensitivity analysis limiting to 184 patients with a normal summed stress score (≤3), SUA was associated with both CFR (β = -0.14, p = 0.037) and stress MBF (β = -0.16, p = 0.048).
null: Association between serum uric acid level and coronary vascular function*.
Outcome variable Model adjustment Regression coefficient (Standard error) p-value All patients (n = 382) Coronary flow reserve None -0.12 (0.05) 0.015 Age and sex -0.11 (0.05) 0.022 Age, sex, diabetes, and SSS -0.08 (0.05) 0.101 Age, sex, diabetes, SSS, and Cr -0.05 (0.05) 0.255 Age, sex, diabetes, SSS, Cr and gout -0.07 (0.05) 0.138 Myocardial blood flow at stress None -0.28 (0.06) <0.001 Age and sex -0.22 (0.06) <0.001 Age, sex, diabetes, and SSS -0.16 (0.05) 0.002 Age, sex, diabetes, SSS, and Cr -0.15 (0.05) 0.007 Age, sex, diabetes, SSS, Cr and gout -0.14 (0.05) 0.01 Patients with SSS≤3 (n = 184) Coronary flow reserve None -0.15 (0.06) 0.023 Age and sex -0.16 (0.07) 0.016 Age, sex, diabetes -0.16 (0.07) 0.014 Age, sex, diabetes, and Cr -0.13 (0.06) 0.054 Age, sex, diabetes, Cr and gout -0.14 (0.07) 0.037 Myocardial blood flow at stress None -0.23 (0.08) 0.003 Age and sex -0.19 (0.08) 0.014 Age, sex, diabetes -0.18 (0.08) 0.019 Age, sex, diabetes, and Cr -0.15 (0.08) 0.048 Age, sex, diabetes, Cr and gout -0.16 (0.08) 0.048
- 7 SSS: summed stress score, Cr: serum creatinine
- 8 *Log transformed values of serum uric acid level, coronary flow reserve, myocardial blood flow at stress, and serum creatinine were used
Characteristics of the diabetic (n = 167) and non-diabetic (n = 215) subgroups are presented in Tables 3 and 4. The mean age (SD) was 67.1 (10.3) years in the diabetic subgroup and 69.4 (13.8) in the non-diabetic subgroup. Median [IQR] BMI was 32.0 [28.0, 38.0] kg/m
null: Characteristics of patients with diabetes.
N Overall Hyperuricemia Normouricemia p-value 167 103 64 Mean ± SD, median [IQR] or percentage Uric acid level, mg/dl 7.6 ± 2.77.4 [5.6, 9.3] 9.2 ± 2.18.9 [7.6, 10.2] 5.1 ± 1.25.2 [4.4, 6.1] <0.001 Age, years 67.1 ± 10.368.0 [60.0, 75.0] 68.4 ± 10.068.0 [61.0, 77.0] 65.0 ± 10.466.0 [59.0, 73.0] 0.042 Female 34 37 28 0.243 Body mass index, kg/m2 32.0 [28.0, 38.0] 33.0 [28.0, 39.0] 31.5 [27.5, 36.0] 0.169 Comorbidities Hypertension 90 94 84 0.037 Gout 38 47 25 <0.001 Smoking 4 4 5 1 Coronary artery disease 30 28 33 0.523 Heart failure 13 18 3 0.004 Dyslipidemia 79 80 78 0.819 Serum creatinine, mg/dl a 1.3 [1.0, 1.9] 1.4 [1.1, 1.9] 1.1 [0.9, 2.0] 0.115 LDL level, mg/dl b 79.0 [56.0, 98.0] 79.5 [57.0, 98.0] 76.0 [55.0, 95.0] 0.531 Medications Beta blockers 73 72 75 0.656 Calcium channel blockers 29 38 16 0.002 Nitrates 26 30 20 0.163 ACE inhibitors 47 43 53 0.19 Diuretics 56 68 36 <0.001 Aspirin 72 74 70 0.625 Statins and other lipid lowering drugs 75 75 75 0.972 Colchicine 13 19 3 <0.001 Xanthine oxidase inhibitors 29 36 19 0.018 Cardiac function Heart rate at rest, per minute 70.0 [63.0, 80.0] 71.0 [64.0, 80.0] 69.5 [63.0, 80.0] 0.567 Systolic blood pressure at rest, mmHg 143.0 [125.0, 170.0] 144.0 [130.0, 172.0] 139.0 [122.0, 164.0] 0.204 LVEF at rest, %c 51.0 [39.0, 62.0] 50.5 [35.0, 62.0] 52.0 [42.0, 60.0] 0.53 LVEF at stress, %d 54.0 [40.0, 66.0] 54.0 [39.0, 65.0] 55.0 [44.5, 70.0] 0.205 Sum stress score 6.0 [0.0, 15.0] 6.0 [0.0, 15.0] 4.5 [0.0, 15.0] 0.597 Sum difference score 2.0 [0.0, 7.0] 3.0 [0.0, 7.0] 2.0 [0.0, 8.0] 0.864 Sum rest score 0.0 [0.0, 6.0] 1.0 [0.0, 6.0] 0.0 [0.0, 7.0] 0.362 Myocardial blood flow at rest, mL/min/g 0.9 [0.7, 1.2] 0.9 [0.7, 1.2] 0.9 [0.8, 1.2] 0.291 Myocardial blood flow at stress, mL/min/g 1.4 [1.1, 2.1] 1.5 [1.0, 2.1] 1.4 [1.2, 1.8] 0.709 Coronary flow reserve 1.6 [1.2, 2.1] 1.5 [1.2, 2.1] 1.6 [1.2, 2.0] 0.683
- 13 SD: standard deviation, LDL: low density lipoprotein, ACE: angiotensin converting enzyme, LVEF: left ventricle ejection fraction
- 14 P-values are for the comparisons between hyperuricemia and normouricemia.
- 9 a Missing in 0% of the hyperuricemia group and 2% of the normouricemia group
- 10 b Missing in 17% of the hyperuricemia group and 17% of the normouricemia group
- 11 c Missing in 5% of the hyperuricemia group and 2% of the normouricemia group
- 12 d Missing in 1% of the hyperuricemia group and 6% of the normouricemia group
null: Characteristics of patients without diabetes.
N Overall Hyperuricemia Normouricemia p-value 215 105 110 Mean ± SD, median [IQR] or percentage Uric acid level, mg/dl 6.9 ± 2.56.7 [5.3, 8.3] 8.9 ± 2.08.3 [7.3, 9.9] 5.1 ± 1.25.3 [4.6, 5.9] <0.001 Age, years 69.4 ± 13.870.0 [60.0, 80.0] 69.4 ± 13.770.0 [58.0, 79.0] 69.4 ± 14.071.0 [60.0, 81.0] 0.999 Female 37 36 38 0.763 Body mass index, kg/m2 27.0 [24.0, 31.0] 27.0 [25.0, 31.0] 27.0 [24.0, 31.0] 0.554 Comorbidities Hypertension 81 88 74 0.013 Gout 22 31 14 0.002 Smoking 8 8 8 0.863 Coronary artery disease 25 28 22 0.343 Heart failure 9 14 5 0.015 Dyslipidemia 71 74 68 0.303 Serum creatinine, mg/dl a 1.2 [0.9, 1.7] 1.4 [1.0, 2.2] 1.0 [0.8, 1.2] <0.001 LDL level, mg/dl b 79.5 [62.0, 95.5] 79.0 [58.0, 92.0] 80.0 [67.0, 101.0] 0.421 Medications Beta blockers 65 70 61 0.169 Calcium channel blockers 24 26 22 0.526 Nitrates 14 18 9 0.057 ACE inhibitors 36 35 36 0.934 Diuretics 40 50 31 0.006 Aspirin 61 61 61 0.938 Statins and other lipid lowering drugs 68 72 63 0.156 Colchicine 5 7 3 0.295 Xanthine oxidase inhibitors 17 24 11 0.012 Cardiac function Heart rate at rest, per minute 70.0 [62.0, 80.0] 71.0 [63.0, 79.0] 69.0 [61.0, 80.0] 0.403 Systolic blood pressure at rest, mmHg 142.0 [128.0, 158.0] 140.0 [125.0, 157.0] 143.0 [130.0, 158.0] 0.427 LVEF at rest, %c 55.0 [42.0, 63.0] 50.0 [34.0, 62.0] 57.0 [46.0, 64.0] 0.003 LVEF at stress, %d 59.0 [45.0, 68.0] 55.0 [39.0, 64.0] 63.0 [51.0, 70.0] 0.002 Sum stress score 2.0 [0.0, 13.0] 5.0 [0.0, 18.0] 0.0 [0.0, 7.0] 0.004 Sum difference score 0.0 [0.0, 5.0] 0.0 [0.0, 6.0] 0.0 [0.0, 4.0] 0.174 Sum rest score 0.0 [0.0, 4.0] 0.0 [0.0, 7.0] 0.0 [0.0, 2.0] 0.004 Myocardial blood flow at rest, mL/min/g 1.0 [0.8, 1.3] 0.9 [0.8, 1.2] 1.0 [0.8, 1.3] 0.166 Myocardial blood flow at stress, mL/min/g 1.6 [1.1, 2.1] 1.4 [1.1, 1.9] 1.8 [1.2, 2.5] <0.001 Coronary flow reserve 1.6 [1.2, 1.9] 1.5 [1.2, 1.7] 1.7 [1.3, 2.2] 0.002
- 19 SD: standard deviation, LDL: low density lipoprotein, ACE: angiotensin converting enzyme, LVEF: left ventricle ejection fraction
- 20 P-values are for the comparisons between hyperuricemia and normouricemia.
- 15 a Missing in 1% of the hyperuricemia group and 2% of the normouricemia group
- 16 b Missing in 23% of the hyperuricemia group and 25% of the normouricemia group
- 17 c Missing in 2% of the hyperuricemia group and 3% of the normouricemia group
- 18 d Missing in 4% of the hyperuricemia group and 6% of the normouricemia group
null: Association between serum uric acid level and coronary vascular function for patients stratified by diabetes*.
Outcome variable Model adjustment Regression coefficient (Standard error) p-value With diabetes Coronary flow reserve None -0.02 (0.08) 0.803 Age and sex -0.01 (0.08) 0.876 Age, sex, SSS and Cr 0.01 (0.07) 0.856 Age, sex, SSS, Cr and gout -0.003 (0.08) 0.969 Myocardial blood flow at stress None -0.15 (0.09) 0.1 Age and sex -0.14 (0.09) 0.111 Age, sex, SSS, and Cr -0.11 (0.08) 0.187 Age, sex, SSS, Cr and gout -0.10 (0.08) 0.242 Without diabetes Coronary flow reserve None -0.21 (0.06) 0.001 Age and sex -0.20 (0.06) 0.003 Age, sex, SSS, and Cr -0.14 (0.07) 0.038 Age, sex, SSS, Cr and gout -0.15 (0.07) 0.022 Myocardial blood flow at stress None -0.37 (0.08) <0.001 Age and sex -0.27 (0.08) <0.001 Age, sex, SSS and Cr -0.19 (0.07) 0.01 Age, sex, SSS, Cr and gout -0.19 (0.07) 0.01
- 21 SSS: summed stress score, Cr: serum creatinine
- 22 *Log transformed values of serum uric acid level, coronary flow reserve, myocardial blood flow at stress, and serum creatinine were used.
However, among patients with no diabetes, SUA (see S1 and S2 Figs) had a negative correlation with both CFR (r = -0.22, p = 0.001) and stress MBF (r = -0.31, p<0.001) in the unadjusted analysis. In multivariable linear regression adjusting for age, sex, summed stress score (a measure of the extent of myocardial scar and ischemia), serum creatinine and diagnosis of gout, a higher SUA remained modestly associated with a lower CFR (β = -0.15, p = 0.02) and stress MBF (β = -0.19, p = 0.01).
The potential causal role of SUA on CAD and other cardiometabolic diseases has been under debate over the past few decades. While a number of epidemiologic studies showed positive associations between SUA and CAD or cardiovascular disease,[[
This present study provides one of the most comprehensive evaluations of myocardial perfusion and coronary vascular function in relation to SUA levels. We examined not only the overall relationship between SUA and coronary vascular function in patients with and without prior myocardial scar or ischemia, but also the relationship stratified by the presence of diabetes. Since not all patients with high SUA have gout, an independent risk factor for cardiovascular disease, our analysis was adjusted for the presence of gout. As a result, we noted a modest negative association between SUA and coronary vascular dysfunction in patients without overt CAD (i.e., normal summed stress score) and those without diabetes, but not in the diabetic group. The lack of a significant association in diabetic patients may be explained by the fact that the modest effect of SUA on CFR seen in non-diabetic patients is likely overshadowed by the known strong association of diabetes and associated metabolic abnormalities (hyperglycemia and insulin resistance) with coronary microvascular dysfunction.[[
Another potential explanation for the difference in the association of SUA with coronary vascular dysfunction by diabetes may be related to the difference in the severity of underlying CAD between the diabetic and non-diabetic groups in the study cohort. In the diabetic group, 41.9% had a normal summed stress score (i.e., ≤3) while 53% did in the non-diabetic group. As seen in the sensitivity analysis limited to those with a normal summed stress score (≤3), SUA unlikely has a role in determining coronary vascular function in patients with established myocardial damages even if SUA is causally related to CAD.
This study has limitations. First, as discussed earlier, this study is based at a single academic center, in which the study patients were referred for a PET test for a clinical reason. Thus, the results may not be generalizable to those with hyperuricemia and no clinical symptoms of CAD or subtle CAD. Second, as this is a cross-sectional study, the causal relationship between SUA levels and coronary vascular function cannot be determined. Some patients may maintain high SUA levels for a long time unless they are treated. However, to reduce exposure misclassification (i.e., SUA level) in the study cohort, we required all the SUA levels to be drawn within 6 months from the PET test. Third, while the final models were adjusted for several important predictors of CAD risk including age, sex, renal function, gout diagnosis, and a summed stress score (i.e., a marker of myocardial scar and ischemia), there may be residual confounding. Fourth, this study is the first and largest study that investigated an association between SUA and coronary vascular function using a cardiac PET, but further confirmation of our results is necessary in a larger and more generalizable setting.
In conclusion, this cross-sectional analysis showed a modest inverse association between high SUA levels and coronary vascular function in patients without diabetes after adjusting for age, sex, serum creatinine, gout diagnosis and the extent and severity of perfusion defects. Such association was not noted in patients with diabetes. While our results need to be confirmed in different settings, this present study suggests that the effect of hyperuricemia on coronary vascular function or CAD differs by diabetes status and may be more evident in patients without diabetes. Furthermore, this study highlights the need for future research on the association between the change in SUA and the change in coronary vascular function over time, particularly in patients without diabetes.
null. Pearson correlations between serum uric acid levels and myocardial blood flow (MBF) at stress.(DOCX)
null. Pearson correlations between serum uric acid levels and coronary flow reserve (CFR).(DOCX)
SCK is supported by a grant from the NIH R21 AR069271. DHS is supported by the NIH grants K24 AR055989, P60 AR047782, U34 AR063911, and R01 HL119718.
By Seoyoung C. Kim, Writing – original draft; Nishant R. Shah, Writing – review & editing; James R. Rogers, Writing – review & editing; Courtney F. Bibbo, Writing – review & editing; Marcelo F. Di Carli, Writing – review & editing and Daniel H. Solomon, Writing – review & editing