Moo-Yong Rhee

No differences of carotid intima-media thickness between young patients with ankylosing spondylitis and healthy controls.

OBJECTIVE Accelerated atherosclerosis in inflammatory rheumatic diseases such as ankylosing spondylitis (AS) stands out among the leading causes of morbidity and mortality. We assessed the correlation between subclinical carotid atherosclerosis and its related clinical parameters in AS patients. METHODS Twenty-eight patients (23 males, 5 females) with AS and 27 sex- and age-matched controls were consecutively recruited to this study. We estimated the carotid intima-media thickness (IMT) and parameters related to arterial elastic properties, including the distensibility coefficient (DC), stiffness index (beta), and incremental elastic modulus (E(inc)) using high-resolution ultrasonography. Serum levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1) were measured using enzyme-linked immunosorbent assay (ELISA). RESULTS Carotid IMT values and arterial elastic parameters in AS patients showed no statistical significance compared to those of controls (0.57+/-0.07 vs 0.55+/-0.05, p=0.387 for IMT, 28.45+/-9.23 vs 31.93+/-9.52, p=0.175 for DC, 2.32+/-0.18 vs 2.29+/-0.15, p=0.559 for stiffness index (beta), and 0.14+/-0.05 vs 0.12+/-0.03, p=0.116 for E(inc)). The serum level of IL-6 in AS patients was significantly different compared with controls (p=0.001), but not in serum levels of TNF-alpha and MCP-1 (p=0.162, p=0.087, respectively). Carotid IMT and all arterial elastic parameters calculated in this study were not found to be associated with serum levels of TNF-alpha, IL-6, and MCP-1. CONCLUSION This cross-sectional study showed that carotid IMT and parameters related with arterial elastic properties in young AS patients without clinically evident cardiovascular risk factors were not different from those of sex- and age-matched healthy controls. Serum levels of TNF-alpha, IL-6, and MCP-1 did not reflect the degree of carotid subclinical atherosclerosis. However, these findings should be confirmed further in a larger population.

Novel genetic variations associated with salt sensitivity in the Korean population

Salt sensitivity is a risk factor for cardiovascular morbidity and mortality. To date, only a few genetic variations have been identified as being associated with salt sensitivity. This study aimed to estimate the prevalence of salt sensitivity in the Korean population and to identify genetic variants affecting its development. A total of 101 Korean participants consumed a low-salt diet for 7 days followed by a high-salt diet for 7 additional days. Salt sensitivity was determined by noting any significant elevation in the 24-h mean arterial blood pressure. To determine genetic variants affecting salt sensitivity, 36 single-nucleotide polymorphisms (SNPs) that were previously reported to be associated with hypertension were tested for any associations with salt sensitivity. Of the 101 subjects, 28 (27.7%) were determined to have salt sensitivity. Out of the 36 SNPs tested, four were significantly associated with salt sensitivity after adjusting for confounding factors: rs2681472 in ATPase, Ca++ transporting, plasma membrane 1 (ATP2B1), rs7961152 in branched chain aminotransferase 1 (BCAT1), rs16998073 in fibroblast growth factor 5 (FGF5) and rs2398162 in LOC100132798. For rs3754777 in serine threonine kinase 39 (STK39) and rs1937506, associations with salt sensitivity were observed before adjusting for confounding factors. Haplotype analysis revealed that the A-C haplotype of rs3754777–rs6749447 in STK39 was more frequent in the salt-sensitive group compared with the salt-resistant group, and was associated with salt sensitivity. This study estimates the prevalence of salt sensitivity in the Korean population and demonstrates a novel association between salt sensitivity and the ATP2B1, BCAT1, FGF5, LOC100132798 and STK39 genetic variations.

Intima-media Thickness and Arterial Stiffness of Carotid Artery in Korean Patients with Behçet's Disease

Behçets disease (BD) is a systemic vasculitis involving diverse sizes of arteries and veins. We performed this study to evaluate the vascular changes by assessment of the arterial stiffness and intima-media thickness (IMT) of carotid artery in Korean patients with BD. Forty-one patients with BD and age-, and sex-matched 53 healthy subjects were recruited in this study. Carotid arterial stiffness and IMT were assessed by using high-resolution B-mode ultrasonography. Arterial stiffness parameters such as carotid arterial distensibility coefficient, stiffness index, and incremental elastic modulus (Einc) were significantly increased in BD patients compared with those in healthy subjects, but not in IMT. Positive relationship was noted between age and IMT, whereas age of onset was significantly associated with arterial stiffness in BD. This finding suggests impaired endothelial function before visible structural changes of arterial wall in BD. Age and age of onset may be an independent risk factor for carotid IMT and arterial stiffness, respectively. Further studies in more large populations are required to confirm our results.

Estimation of 24-Hour Urinary Sodium Excretion Using Spot Urine Samples

The present study evaluated the reliability of equations using spot urine (SU) samples in the estimation of 24-hour urine sodium excretion (24-HUNa). Equations estimating 24-HUNa from SU samples were derived from first-morning SU of 101 participants (52.4 ± 11.1 years, range 24–70 years). Equations developed by us and other investigators were validated with SU samples from a separate group of participants (n = 224, 51.0 ± 10.9 years, range 24–70 years). Linear, quadratic, and cubic equations were derived from first-morning SU samples because these samples had a sodium/creatinine ratio having the highest correlation coefficient for 24-HUNa/creatinine ratio (r = 0.728, p < 0.001). In the validation group, the estimated 24-HUNa showed significant correlations with measured 24-HUNa values. The estimated 24-HUNa by the linear, quadratic, and cubic equations developed from our study were not significantly different from measured 24-HUNa, while estimated 24-HUNa by previously developed equations were significantly different from measured 24-HUNa values. The limits of agreement between measured and estimated 24-HUNa by six equations exceeded 100 mmol/24-hour in the Bland-Altman analysis. All equations showed a tendency of under- or over-estimation of 24-HUNa, depending on the level of measured 24-HUNa. Estimation of 24-HUNa from single SU by equations as tested in the present study was found to be inadequate for the estimation of an individual’s 24-HUNa.

Blood Pressure Lowering Effect of Korea Ginseng Derived Ginseol K-g1

We investigated the effect of Panax ginseng extract, which is rich in the ginsenoside protopanaxatriol (Ginseol K-g1), on blood pressure (BP). Adults over 20 years old with a systolic BP (SBP) between 120 and 159 mm Hg or a diastolic BP (DBP) between 80 and 99 mm Hg were included. At the end of an initial 2-week washout period, the patients were divided into three groups: the control group (placebo), the low-dose Ginseol K-g1 group (100 mg), and the high-dose Ginseol K-g1 (300 mg) group. The primary end point was the difference in seated SBP (seSBP) and seated DBP (seDBP) changes between the placebo and Ginseol K-g1 groups after 8 weeks of treatment. A total of 90 subjects participated in the study (mean age; 55.2 ± 11.8 years, 43 males). At week 8, levels of seSBP and seDBP were significantly decreased from baseline in the high-dose Ginseol K-g1 group (-3.1 mm Hg and -2.3 mm Hg, respectively, p < 0.05). In contrast, there was no significant decrease in seSBP or seDBP in the control or low-dose Ginseol K-g1 groups. No significant difference of seSBP and seDBP was identified among the three treatment groups at week 8. In patients who had a seSBP ≥ 130 mm Hg or an seDBP ≥ 85 mm Hg, the high dose of Ginseol K-g1 decreased the BP compared with the control group at week 4; however, there was no significant difference at week 8. The proportions of patients who experienced adverse events were comparable among the treatment groups. In conclusion, Ginseol K-g1 has a favorable effect on BP after 4 weeks of treatment, especially at a high dose. However, the effect is not maintained over 8 weeks. (Clinical trial registration information is available at http://www.clinicaltrials.gov , identifier: NCT01483430.).

Brachial-ankle pulse wave velocity for the prediction of the presence and severity of coronary artery disease.

Abstract The predictability of brachial-ankle pulse wave velocity (baPWV) for the presence and severity of coronary artery disease (CAD) was investigated by measuring baPWV in 501 subjects scheduled for coronary angiography. Severity of CAD was measured using modified Gensini stenosis score (GSS) and classified as a vessel disease score (VDS) of 0–3. The presence of CAD was defined as diameter stenosis > 50%. Subjects were grouped in tertile by level of baPWV (<14, 14–17,  >17 m/s). Subjects with CAD showed higher mean age, prevalence of men and diabetes, and systolic blood pressure. The prevalence of hypertension, use of antihypertensive medications and use of statin was not different. Subjects with CAD had higher baPWV than subjects without CAD (16.70 ± 3.46 versus 15.21 ± 3.19 m/s, p < 0.001). Multiple linear regression analysis showed significant correlation of baPWV and modified GSS (p = 0.0337). ANCOVA adjusted with age, gender, body mass index, presence of hypertension or diabetes, status of smoking, use of antihypertensive medications and risk of hypercholesterolemia showed a statistically significant association of baPWV with VDS (p < 0.0001). Highest tertile of baPWV had a statistically significant effect on the severity of CAD from an ANCOVA model. The predictive power of highest tertile of baPWV for the presence of CAD was 3.600 [95% confidence interval (CI) 1.884–6.881, p < 0.0001]. It is concluded that increased baPWV is a reliable predictor of the presence and severity of CAD, suggesting that baPWV > 17 m/s may be a threshold value for the presence and severity of CAD.

Subclinical Renal Insufficiency Range of Estimated Glomerular Filtration Rate and Microalbuminuria Are Independently Associated with Increased Arterial Stiffness in Never Treated Hypertensives

Background and Objectives Microalbuminuria (MAU) and decreased estimated glomerular filtration rate (eGFR) are risk factors for cardiovascular disease (CVD) in patients with hypertension. However, in hypertensive patients with normal or minimally reduced eGFR (≥60 mL/min/1.73 m2) and with normo- or MAU, the value of combined estimation of eGFR and urine microalbumin for the risk assessment has not been widely reported. We evaluated the association between arterial stiffness and the combined estimation of eGFR and urine microalbumin. Subjects and Methods Subjects with never treated hypertension and normal or minimally reduced eGFR were evaluated (n=491, 50.1±10.4 years). eGFR was calculated by the simplified Modification of Diet in Renal Disease formula. Urinary albumin-to-creatinine ratio (UACR) was assessed with spot urine. Arterial stiffness was assessed with heart-femoral pulse wave velocity (hfPWV). All subjects were divided into four groups; group 1, eGFR ≥90 mL/min/1.73 m2 (normal eGFR) and normo-albuminuria (NAU); group 2, eGFR 89.9-60 mL/min/1.73 m2 (minimally reduced eGFR) and NAU; group 3, normal eGFR and MAU; group 4, minimally reduced eGFR and MAU. Results Group 1 had the lowest hfPWV (964.6±145.4; group 2, 1013.5±168.9; group 3, 1058.2±238.0; group 4, 1065.8±162.9 cm/sec). Analysis adjusting age, sex, body mass index, heart rate and mean arterial pressure showed significantly lower hfPWV of group 1 compared to group 2 (p=0.032) and 3 (p=0.007). Multiple regression analysis showed a significant association of hfPWV with logUACR {beta=0.096, 95% confidence interval (CI) 8.974-60.610, p=0.008} and eGFR (beta=-0.069, 95% CI -1.194 - -0.005, p=0.048). Conclusion Minimally reduced eGFR or MAU is independently associated with increased arterial stiffness, indicating greater CVD risk.

High Sodium Intake: Review of Recent Issues on Its Association with Cardiovascular Events and Measurement Methods

There has been a long-known association between high dietary sodium intake and hypertension, as well as the increased risk of cardiovascular disease. Reduction of sodium intake is a major challenge for public health. Recently, there have been several controversial large population-based studies regarding the current recommendation for dietary sodium intake. Although these studies were performed in a large population, they aroused controversies because they had a flaw in the study design and methods. In addition, knowledge of the advantages and disadvantages of the methods is essential in order to obtain an accurate estimation of sodium intake. I have reviewed the current literatures on the association between sodium intake and cardiovascular events, as well as the methods for the estimation of sodium intake.

Association between 24-hour ambulatory blood pressure and erythrocyte n-3 polyunsaturated fatty acids in Korean subjects with hypertension

N-3 polyunsaturated fatty acids (PUFAs) are known to have antihypertensive properties, but the association between 24-hour ambulatory blood pressure and the tissue content of n-3 PUFA remains controversial. The purpose of the present study was to investigate the hypothesis that the level of erythrocyte n-3 PUFA is inversely related with 24-hour ambulatory blood pressure after adjustment for relevant confounders. Fifty-one male and 49 female Korean patients were included in this study. Twenty-seven of the patients were defined as having hypertension. There were significant differences in age, body mass index, sex, marital status, and family history of hyperlipidemia between hypertensive and nonhypertensive subjects, and these factors were therefore considered to be confounding factors. Multivariate-adjusted regression analysis showed that erythrocyte fatty acids were not significantly associated with the risk of hypertension after adjusting for confounders. However, Pearson correlation analysis showed that 24-hour ambulatory systolic blood pressure (SBP) was significantly and negatively correlated with n-3 PUFA (r = -0.228, P = .027) and eicosapentaenoic acid (r = -0.270, P = .008), but not with docosahexaenoic acid (r = -0.156, P = .131). Multivariate-adjusted regression analysis also showed that intake of protein, vitamin B(2), vitamin E, and cholesterol increased the risk of hypertension after adjusting for confounders. In addition, Pearson correlation analysis showed that fat and cholesterol consumption was positively correlated with SBP, but carbohydrate intake was negatively correlated with SBP. In conclusion, erythrocyte n-3 PUFA did not reduce the risk of hypertension but were negatively correlated with 24-hour ambulatory SBP in the Korean population.

Elevation of Morning Blood Pressure in Sodium Resistant Subjects by High Sodium Diet

The present study evaluated the response of blood pressure (BP) by dietary sodium in sodium resistant (SR) subjects. One hundred one subjects (mean age, 46.0 yr; 31 hypertensives) were admitted and given low sodium-dietary approaches to stop hypertension (DASH) diet (LSD, 100 mM NaCl/day) for 7 days and high sodium-DASH diet (HSD, 300 mM NaCl/day) for the following 7 days. On the last day of each diet, 24 hr ambulatory BP was measured. Morning systolic BP (SBP) and diastolic BP (DBP) were elevated after HSD in all subjects (P < 0.01), but daytime SBP and DBP were not changed (P > 0.05). In hypertensive subjects, morning DBP elevation was greater than daytime DBP elevation (P = 0.036), although both DBPs were significantly elevated after HSD. The augmented elevation of morning DBP in hypertensive subjects was contributed by the absolute elevation of morning DBP (P = 0.032) and relative elevation to daytime DBP (P = 0.005) in sodium resistant (SR) subjects, but not by sodium sensitive subjects. Although there was no absolute elevation, SR subjects with normotension showed a relative elevation of morning SBP compared to daytime SBP change after HSD (P = 0.009). The present study demonstrates an absolute and relative elevation of morning BP in SR subjects by HSD.