Objective:We aimed to investigate the efficacy and safety of a combination of fimasartan 30 mg and moderate-intensity statins in patients with hypertension and dyslipidemia in a real-world setting. Methods:This non-interventional, multicenter, prospective observational study included 5,264 patients receiving a combination of fimasartan 30 mg and moderate-intensity statins with 12-week follow-up data. Co-primary efficacy outcomes were the percentage of patients that achieved target blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C) control. Safety outcomes included adverse drug reactions and treatment-emergent adverse events. Results:At 12 weeks, the proportion of patients individually achieving target BP and LDL-C was 74.4% (95% confidence interval [CI], 73.2-75.5) and 85.6% (95% CI, 84.5-86.8), respectively. The proportion of patients achieving simultaneous control of target BP and LDL-C was 65.6% (95% CI, 64.1-67.2). The median (interquartile range; IQR) differences in systolic and diastolic BPs from baseline to 12 weeks were -8.0 mmHg (-19.0 to 0.0) and -4.0 mmHg (-11.0 to 0.0), respectively (both p-values <0.0001). The median (IQR) percentage change in LDL-C from baseline to 12 weeks was -11.5% (-33.5 to 4.8) (p<0.0001). No significant adverse drug reactions or serious treatment-emergent adverse events were reported during the study period. Conclusion:Findings of this study demonstrate that a combination of fimasartan 30 mg and moderate-intensity statins results in excellent control of BP and LDL-C levels without any safety issues.
Objective:We examined the distribution of low-density lipoprotein cholesterol (LDL-C) levels and compared the hazards of myocardial infarction (MI), stroke, and their composite according to LDL-C concentration in young adults. Methods:This was a nationwide, population-based study. From the Korean National Health Insurance Service database (2002-2022), we identified adults aged 20-39 years without prior MI or stroke who underwent at least 1 health examination between 2009 and 2012 (n=6,458,006). The hazards of MI, stroke, and their composite were evaluated across LDL-C levels. Results:During a median follow-up of 12.6 years, 47,107 MIs, 28,536 strokes, and 73,897 composite events occurred. The hazard of outcomes showed a J-shaped association with LDL-C levels, with the lowest hazard observed around 90-110 mg/dL. Above this range, the hazard increased progressively with rising LDL-C levels. In analyses based on LDL-C categories, levels ≥130 mg/dL were associated with significantly increased hazards of outcomes, with the highest hazards observed at ≥160 mg/dL. The elevated hazards in the higher LDL-C categories were more pronounced in individuals with abdominal obesity and current smokers for all 3 outcomes, and in those with higher body mass index categories, low high-density lipoprotein-cholesterol, and hypertriglyceridemia for MI and the composite outcome. Conclusion:Among young adults, cardiovascular risk demonstrated a J-shaped association with LDL-C levels. Risks increased progressively beyond approximately 90-110 mg/dL, especially in the presence of other cardiometabolic risk factors. These findings underscore the importance of lipid monitoring and cardiovascular risk assessment even in young adults, particularly those with concurrent risk factors.
Tirzepatide is the first dual glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 (GLP-1) receptor agonist to be approved for the treatment of diabetes mellitus. The SURPASS trials investigated the efficacy and safety of tirzepatide, both as monotherapy and as add-on therapy, in comparison with placebo, basal insulin, semaglutide, or dulaglutide in patients with type 2 diabetes. Tirzepatide at doses of 5 mg, 10 mg, or 15 mg produced significant reductions in hemoglobin A1c levels (-1.87% to -2.58%) and body weight (-6.2 to -12.9 kg) in patients with type 2 diabetes, without increasing the risk of serious hypoglycemia. Tirzepatide also improved lipid parameters and lowered blood pressure. Most of the observed adverse events were mild gastrointestinal symptoms, and the occurrence rate of these events was comparable to that associated with GLP-1 receptor agonists such as semaglutide (1 mg) or dulaglutide (0.75 mg). In this review, we summarize the pharmacodynamics and pharmacokinetics of tirzepatide, review the findings from the phase III SURPASS clinical trials, and discuss the anticipated beneficial effects of tirzepatide on the prevention and management of atherosclerosis and dyslipidemia in patients with type 2 diabetes mellitus.
Objective:Familial hypercholesterolemia (FH) is an autosomal dominant disorder associated with a markedly elevated, yet heterogeneous, risk of atherosclerotic cardiovascular disease (ASCVD). To improve identification of highest-risk individuals, the International Atherosclerosis Society (IAS) introduced the concept of "severe FH." This study investigated clinical and molecular genetic risk factors associated with severe FH in Korean patients. Methods:Patients enrolled in the Korean FH Registry were analyzed. Severe FH was defined according to IAS criteria, including the presence of ASCVD, subclinical atherosclerosis detected by imaging, or markedly elevated low-density lipoprotein cholesterol levels together with cardiovascular risk factors. FH-associated genes were analyzed using whole-exome sequencing or targeted exome sequencing. Clinical and genetic characteristics were compared between patients with severe and non-severe FH. Results:Among 296 patients, 172 (58%) had severe FH. Compared with patients with non-severe FH, those with severe FH were older, more frequently male, and had higher prevalence of smoking, hypertension, and diabetes mellitus. Triglyceride levels, lipoprotein(a), and high-sensitivity C-reactive protein concentrations were also significantly higher in the severe FH group. Although the frequency of pathogenic or likely pathogenic variants was numerically higher in severe FH patients (38.3% vs. 30.7%), this difference did not reach statistical significance, likely due to limited statistical power (p=0.170). Conclusion:Korean patients with severe FH exhibited distinct clinical characteristics, including older age, male predominance, and a greater burden of cardiometabolic risk factors. However, the presence and type of pathogenic or likely pathogenic variants in FH-associated genes did not differ significantly between severe and non-severe FH groups.
Objective:Significant sex differences have been observed in the diagnosis and treatment of familial hypercholesterolemia (FH). This study aimed to clarify sex differences among Japanese FH patients. Methods:We assessed Japanese patients who had been clinically diagnosed with heterozygous FH (HeFH) at our hospital from 1990 to 2022 (n=1,273). We compared variables that were associated with the diagnosis and treatment of HeFH and the attainment rate of low-density lipoprotein (LDL)-cholesterol treatment target between male and female patients. We used the Cox proportional hazards model to assess factors associated with major adverse cardiac events (MACEs) between male and female sexes. Results:Female patients diagnosed with HeFH were significantly older than male patients (51 vs. 46 years, p<0.001). The median follow-up period was 10.9 years. Compared with female patients, male patients had significantly lower median LDL-cholesterol levels at baseline (236 vs. 244 mg/dL, p<0.001) and follow-up (110 vs. 116 mg/dL, p<0.001). Female patients with HeFH were less likely to achieve the LDL-cholesterol treatment target than male patients (22% vs. 34%, p<0.001). During the follow-up period, 142 MACEs were observed. Male sex was significantly associated with MACEs (hazard ratio, 1.64; 95% confidence interval, 1.14-2.14; p<0.001). Factors associated with MACEs did not significantly differ between male and female. Conclusion:Female patients with HeFH were diagnosed 5 years later than male patients. Moreover, they were less likely to achieve the guideline-recommended LDL-cholesterol level targets. This sex bias represents a significant barrier to clinical care.
