Studies evaluating the relationship between measured 24-h urine sodium (24HUNa), potassium (24HUK) and aortic blood pressure (BP) are rare, and no such study has been performed with an Asian ...population. We evaluated the relationship between 24HUNa, 24HUK, casual BP, 24-h ambulatory BP and aortic BP by analyzing data from 524 participants with valid 24-h urine collection, 24-h ambulatory BP and central BP measurements (mean age 48.1±9.8 years, 193 men). Hypertension was defined as a 24-h ambulatory BP ⩾130/80 mm Hg or current treatment for hypertension (n=219). The participants with hypertension and high 24HUNa (mean 210.5±52.0 mmol per day, range 151.0-432.0) showed higher 24-h systolic (P=0.037) and diastolic BP (P=0.037) and aortic systolic BP (AoSBP, P=0.038) than the participants with hypertension and low 24HUNa (mean 115.7±25.0 mmol per day, range 45.6-150.0), adjusted for confounders. The participants with hypertension and a high ratio of 24HUNa and 24HUK (24HUNa/24HUK, mean 4.03±1.00, range 2.93-7.96) had higher AoSBP than the participants with hypertension and a low 24HUNa/24HUK ratio (mean 2.13±0.54, range 0.53-2.91), adjusted for confounders (P=0.026). The participants with hypertension demonstrated a significant linear relationship between AoSBP and 24HUNa/24HUK ratio that was independent of 24HUNa, according to the multiple regression analysis (P=0.047). In hypertensive patients, 24HUNa/24HUK was positively and more strongly related to AoSBP compared with 24HUNa alone. The result indicates that high sodium and low potassium intake may increase the subsequent risk of cardiovascular disease by elevating AoSBP.
Abstract Background Proper screening and diagnosis of familial hypercholesterolemia (FH) is of critical importance for cardiovascular prevention. However, the clinical diagnosis of FH remains ...difficult partly because its phenotype can vary between different ethnicities. The aim of this study was to determine the clinical features and the best diagnostic approach in Korean FH patients. The predictors of putative pathogenic mutations and coronary artery disease (CAD) were also identified. Methods and Results Ninety-seven patients with low-density lipoprotein-cholesterol >190 mg/dL and xanthoma or FH-compatible family history were included. Putative pathogenic mutations in LDLR , APOB , or PCSK9 genes were identified in 32% of the enrolled patients. The subjects were classified according to four sets of clinical criteria (Simon Broome, Dutch, MEDPED, Japanese). The mutation rates in definite type FH of Simon Broome or Dutch criteria were 35%–37% and lower in our patients than in those of other countries. The mutation detection rate by MEDPED criteria was 67%–75% and higher than those based on other criteria. The best low-density lipoprotein-cholesterol (LDL-C) threshold for predicting mutations was 225 mg/dL. LDL-C was found to be the only independent predictor of mutation carriers, while hypertension and low high-density lipoprotein-cholesterol were predictive of CAD. Conclusions The conventional clinical criteria showed limited mutation detection power and low specificities in Korean FH patients, in whom the best LDL-C threshold for putative mutation was 225 mg/dL. Traditional cardiovascular risk factors were also significantly associated with CAD risk in this population.
Hypertension and dyslipidemia are 2 risk factors of cardiovascular disease that often present simultaneously. Traditionally, treatment of these multiple conditions required separate medications for ...each disease, which may result in poor compliance and thus lead to possible treatment failure. Fixed-dose combination (FDC) therapy with a single pill may be a solution in these situations.
This multicenter, 8-week, randomized, double-blind, Phase III study evaluated the efficacy and safety of FDC treatment with telmisartan (80 mg) and rosuvastatin calcium (20 mg) in Korean patients with mild to moderate hypertension and dyslipidemia. Patients were randomly assigned to 4 groups: (1) FDC drug (80 mg of telmisartan and 20 mg of rosuvastatin); (2) 80 mg of telmisartan; (3) 20 mg of rosuvastatin; or (4) placebo. After 8 weeks of treatment, the change in mean sitting systolic blood pressure (MSSBP) and mean sitting diastolic blood pressure (MSDBP) between the FDC group and the rosuvastatin group, and the percent change in LDL-C between the FDC group and the telmisartan group, were compared.
A total of 210 patients were enrolled in the study (84 in the FDC group, 42 in the rosuvastatin group, 43 in the telmisartan group, and 41 in the placebo group). The reduction in blood pressure was significantly greater in the FDC group than in the rosuvastatin group after 8 weeks of treatment (least squares mean change from baseline, –16.1 1.6 mm Hg vs –1.7 2.2 mm Hg P < 0.001 for MSSBP; –8.8 1.0 mm Hg vs –1.6 1.4 mm Hg P < 0.001 for MSDBP). Least squares mean percent change in LDL-C from baseline was also significantly greater in the FDC group compared with the telmisartan group (–49.3% 2.2% vs 1.5% 3.0%; P < 0.001). FDC therapy also had a higher rate of achieving the treatment goal in both blood pressure (60% vs 45%; P = 0.024) and LDL-C (88.8% vs 16.3%; P < 0.001) compared with rosuvastatin or telmisartan alone, respectively. In regression analysis, higher baseline MSSBP, female sex, and lower body mass index were associated with increased reductions in MSSBP, whereas higher baseline LDL-C level and lower body mass index were associated with greater reductions in LDL-C. There were 48 adverse events in 36 patients (17.3% 36 of 208), and 17 adverse drug reactions in 12 patients (5.8% 12 of 208), indicating no significant differences in short-term safety among study groups.
Treatment with an FDC drug containing telmisartan and rosuvastatin showed similar efficacy in lowering blood pressure and LDL-C levels compared with that of each single drug. ClinicalTrials.gov identifier: NCT01914432.
We investigated whether the combination therapy of low-intensity rosuvastatin and ezetimibe is an useful alternative to moderate-intensity rosuvastatin monotherapy in patients requiring ...cholesterol-lowering therapy.
This was a multicenter randomized, double‐blind study to investigate the safety and efficacy of a fixed-dose combination of rosuvastatin 2.5 mg and ezetimibe 10 mg (R2.5+E10) compared to those of ezetimibe 10 mg monotherapy (E10), rosuvastatin 2.5 mg (R2.5), and rosuvastatin 5 mg monotherapy (R5) in patients with hypercholesterolemia. A total of 348 patients at 15 centers in Korea were screened, and 279 patients were randomized to different groups in the study. Clinical and laboratory examinations were performed at baseline and 4 and 8 weeks after intervention. The primary endpoint was the percentage change of low-density lipoprotein (LDL) cholesterol levels at the 8-week follow-up.
Baseline characteristics were similar among the four groups. There were significant changes in lipid profiles at the 8-week follow-up. A greater decrease in the LDL cholesterol levels (primary endpoint) were found in the R2.5+E10 group (−45.7±18.6%) than in the E10 group (−16.7±14.7%, p<0.0001), R2.5 group (−32.6±15.1%, p<0.0001), and R5 group (−38.9±13.9%, p=0.0003). Similar outcomes were observed regarding the decrease in total cholesterol, non-high-density lipoprotein (HDL) cholesterol, and apolipoprotein B protein. In addition, changes in the triglyceride and HDL levels in the R2.5+E10 group were significantly different compared with those in the E10 group; however, the changes were similar to those in the other treatment groups. In patients with low and moderate risk, all patients achieved the target LDL cholesterol levels in the R2.5+E10 group (100%) compared to 13.0% in the E10 group, 47.6% in the R2.5 group, and 65.2% in the R5 group. Adverse effects were rare and similar in the four groups.
Fixed-dose combination of low-intensity rosuvastatin and ezetimibe was more effective in lowering LDL cholesterol and achieving LDL cholesterol goals than moderate-intensity rosuvastatin monotherapy. These findings suggest that the combination therapy of low-intensity rosuvastatin and ezetimibe is an useful alternative to moderate-intensity rosuvastatin monotherapy for cholesterol management, particularly in patients with low and moderate risk. ClinicalTrials.gov identifier: NCT04652349.
Arterial stiffness and endothelial dysfunction are 2 of the independent predictors for cardiovascular disease, while
(ASH) is a traditional medicinal plant that can improve cardiovascular health. ...This study aimed to investigate the efficacy of the fruit of ASH on vascular function in apparently healthy subjects.
A 12-week, randomized, double-blind, placebo-controlled design, consisting of healthy adults with at least 2 of the following 3 conditions: borderline high blood pressure (BP; 120 mmHg ≤ systolic BP ≤ 160 mmHg or 80 mmHg ≤ diastolic BP ≤ 100 mmHg), smoking (≥10 cigarettes/day), and borderline blood lipid levels (220 ≤ total cholesterol ≤ 240, 130 ≤ low density lipoprotein cholesterol ≤ 165, or 150 ≤ triglyceride ≤ 220 mg/dL). Randomly assigned 76 subjects who received a placebo or 2 doses of ASH fruit (low, 500 mg/day; high, 1,000 mg/day) completed the intervention. Brachial-ankle pulse wave velocity (baPWV), flow-mediated dilation, carotid intima-media thickness, and BP were measured both at baseline and following the 12-week intervention. Endothelial nitric oxide synthase (eNOS) phosphorylation was assessed by western blotting.
Compared with the placebo group, the low-dose group showed more significant changes after the 12-week intervention period in terms of systolic BP (0.1 vs. -7.7 mmHg;
= 0.044), baPWV (31.3 vs. -98.7 cm/s;
= 0.007), and the ratio of phospho-eNOS/eNOS (0.8 vs. 1.22;
= 0.037).
These results suggest that ASH fruit extract at 500 mg/day has the potential to improve BP and arterial stiffness via endothelial eNOS activation in healthy adults with smoking and the tendency of having elevated BP or blood lipid parameters.
Clinical Research Information Service Identifier: KCT0001072.
The aim of this study was to evaluate the safety and efficacy of combination treatment of rosuvastatin with ezetimibe in patients with primary hypercholesterolemia.
This multicenter, randomized, ...double-blind study comprised a main study and an extension study. In the main study, the efficacy and safety of a combination of rosuvastatin (5, 10, and 20 mg) with ezetimibe (10 mg) were compared with those of rosuvastatin (5, 10, and 20 mg) alone. The subjects who achieved the National Cholesterol Education Program Adult Treatment Panel III LDL-C goal in the main study and agreed to a further study were enrolled for the extension study. In the extension study, ezetimibe 10 mg was also administered to subjects who had received rosuvastatin (5, 10, and 20 mg) alone in the main study, and the same treatment was continued for subjects who had received a combination of rosuvastatin with ezetimibe in the main study.
At the end of the main study (week 8), LDL-C levels were significantly lower in subjects receiving combination therapy than in those receiving rosuvastatin monotherapy. Other lipid profiles also significantly improved in the combination therapy group. These improvements continued in the extension study. The combination therapy of rosuvastatin and ezetimibe was generally well tolerated. At the end of the main study, more subjects achieved the National Cholesterol Education Program Adult Treatment Panel III LDL-C goal in the combination therapy group than in the monotherapy group. The increased dosage of rosuvastatin was also well tolerated in the combination treatment.
Combination therapy of ezetimibe 10 mg with varying doses of rosuvastatin that are commonly used in the clinical field improved the lipid profile and allowed more subjects to reach the LDL-C goal in primary hypercholesterolemia compared with rosuvastatin monotherapy. In addition, the efficacy of the combination therapy was maintained for the extended period. Additional beneficial changes were also achieved with combination therapy even in patients who responded well to rosuvastatin monotherapy. ClinicalTrials.gov identifier: NCT03288038.
We evaluated the dose-responsiveness, efficacy, and safety of low-dose triple antihypertensive combination therapies in patients with mild-to-moderate hypertension.
After a 1 to 2-week placebo run-in ...period, 248 patients were randomized to the half-dose triple combination (amlodipine 2.5 mg + losartan 25 mg + chlorthalidone 6.25 mg), third-dose triple combination (amlodipine 1.67 mg + losartan 16.67 mg + chlorthalidone 4.17 mg), quarter-dose triple combination (amlodipine 1.25 mg + losartan 12.5 mg + chlorthalidone 3.13mg), amlodipine 10mg, amlodipine 5mg, losartan 100mg, and placebo groups for 8 weeks. The primary outcome was the mean change in systolic blood pressure (SBP) from baseline to week 8.
The placebo-corrected SBP reductions of the half-dose, third-dose, quarter-dose combination, amlodipine 10 mg, amlodipine 5 mg and losartan 100 mg treatments were -17.2, -19.5, -14.9, -18.5, -11.3 and -9.9 mmHg, respectively. The BP control and response rates were significantly higher in the half-dose, third-dose, and quarter-dose combination groups than in the placebo group (all p < 0.01). Despite no intergroup differences in study drug-related adverse events, ankle circumference increased significantly in the amlodipine group compared to those in the combination treatment groups. The quarter-dose combination, amlodipine 5 mg, and losartan 100 mg groups showed similar SBP reduction and BP response rates. The SBP reduction and BP response rate in the third-dose and half-dose combination groups were not significantly different from those in the amlodipine 10 mg group but superior to those in the losartan 100 mg group.
Low-dose triple combination therapies could be effective as antihypertensive therapies.
ClinicalTrials.gov identifier NCT03897868.
The objective of this study was to evaluate the efficacy and tolerability of a triple combination of amlodipine/losartan/rosuvastatin in patients with hypertension and hypercholesterolemia.
A ...randomized, multicenter, double-blind, placebo-controlled study was conducted. Eligible patients with hypertension and a sitting diastolic blood pressure (SiDBP) of >90 mm Hg and LDL-C levels <250mg/dL were screened. After a 4-week run-in period with therapeutic lifestyle changes and losartan potassium 100mg once daily, patients who met both blood pressure criteria (80 mm Hg ≤ SiDBP < 110 mm Hg) and the LDL-C level criteria (defined in the National Cholesterol Education Program Adult Treatment Panel III cardiovascular risk categories) were randomized to 1 of 3 groups and treated once daily for 8 weeks: losartan potassium 100mg + rosuvastatin 20mg treatment (L/R 100/20) group, amlodipine camsylate 5mg + losartan potassium 100mg treatment (A/L 5/100) group, and amlodipine 5mg+ losartan potassium 100mg + rosuvastatin 20mg (A/L/R 5/100/20) group. The primary efficacy variables were the percent change in LDL-C in the A/L/R 5/100/20 and A/L 5/100 groups and the mean change of SiDBP in the A/L/R 5/100/20 and L/R 100/20 groups after 8 weeks of treatment, relative to baseline values.
A total of 146 patients were enrolled and the demographic characteristics were similar among the 3 treatment groups. After 8 weeks of treatment, the mean (SD) percent change in LDL-C was significantly greater in the A/L/R group than in the A/L group (–48.40% 2.77% vs –6.70% 3.00%; P < 0.0001). Moreover, the mean change in SiDBP was significantly greater in the A/L/R group than in the L/R group (–9.75 0.92 mm Hg vs –1.73 1.03 mm Hg; P < 0.0001). SiDBP and LDL-C reductions in the A/L/R group were comparable to reductions in the A/L and L/R groups, respectively. Ten adverse events were reported in 7 patients (4.83%), and 1 patient from the A/L group (0.69%) experienced 2 adverse drug reactions (tachycardia and face edema), which were mild and resolved without specific treatment. There were no clinically significant tolerability issues during the treatment period.
Triple combination therapy with amlodipine/losartan/rosuvastatin can be an effective therapeutic strategy in patients with hypertension combined with dyslipidemia. These findings will form the foundation of the future development of a single-pill triple combination. ClinicalTrials.gov identifier: NCT02899455.
Abstract
The authors performed this study to investigate the efficacy and safety of a rosuvastatin (RSV)/amlodipine (AML) polypill compared with those of atorvastatin (ATV)/AML polypill. We included ...259 patients from 21 institutions in Korea. Patients were randomly assigned to 1 of 3 treatment groups: RSV 10 mg/AML 5 mg, RSV 20 mg/AML 5 mg, or ATV 20 mg /AML 5 mg. The primary endpoint was the efficacy of the RSV 10.20 mg/AML 5 mg via percentage changes in LDL‐C after 8 weeks of treatment, compared with the ATV 20 mg /AML 5 mg. There was a significant difference in the mean percentage change of LDL‐C at 8 weeks between the RSV 10 mg/AML 5 mg and the ATV 20 mg/AML 5 mg (full analysis set FAS: −7.08%, 95% CI: −11.79 to −2.38,
p
= .0034, per‐protocol analysis set PPS: −6.97%, 95% CI: −11.76 to −2.19,
p
= .0046). Also, there was a significant difference in the mean percentage change of LDL‐C at 8 weeks between the RSV 20 mg/AML 5 mg and the ATV 20 mg/AML 5 mg (FAS: −10.13%, 95% CI: −15.41 to −4.84,
p
= .0002, PPS: −10.96%, 95% CI: −15.98 to −5.93,
p
< .0001). There was no significant difference in the adverse events rates between RSV 10 mg/AML 5 mg, RSV 20 mg/AML 5 mg, and ATV 20 mg/AML 5 mg. In conclusion, while maintaining safety, RSV 10 mg/AML 5 mg and the RSV 20 mg/AML 5 mg more effectively reduced LDL‐C compared with the ATV 20 mg /AML 5 mg (Clinical trial: NCT03951207).
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.
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