scholarly journals Patients With LDLR and PCSK9 Gene Variants Experienced Higher Incidence of Cardiovascular Outcomes in Heterozygous Familial Hypercholesterolemia

2021 ◽  
Vol 10 (4) ◽  
Author(s):  
Takahito Doi ◽  
Mika Hori ◽  
Mariko Harada‐Shiba ◽  
Yu Kataoka ◽  
Daisuke Onozuka ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Primary Outcome ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Cardiovascular Outcomes ◽  
Nonfatal Myocardial Infarction ◽  
Gene Variants ◽  
Low Density ◽  
Gene Variant ◽  
Low Density Lipoprotein Cholesterol

Background Patients with familial hypercholesterolemia who harbored both low‐density lipoprotein receptor ( LDLR ) and PCSK9 (proprotein convertase subtilisin/kexin type 9) gene variants exhibit severe phenotype associated with substantially high levels of low‐density lipoprotein cholesterol. In this study, we investigated the cardiovascular outcomes in patients with both LDLR and PCSK9 gene variants. Methods and Results A total of 232 unrelated patients with LDLR and/or PCSK9 gene variants were stratified as follows: patients with LDLR and PCSK9 ( LDLR/PCSK9 ) gene variants, patients with LDLR gene variant, and patients with PCSK9 gene variant. Clinical demographics and the occurrence of primary outcome (nonfatal myocardial infarction) were compared. The observation period of primary outcome started at the time of birth and ended at the time of the first cardiac event or the last visit. Patients with LDLR/PCSK9 gene variants were identified in 6% of study patients. They had higher levels of low‐density lipoprotein cholesterol ( P =0.04) than those with LDLR gene variants. On multivariate Cox regression model, they experienced a higher incidence of nonfatal myocardial infarction (hazard ratio, 4.62; 95% CI, 1.66–11.0; P =0.003 versus patients with LDLR gene variant). Of note, risk for nonfatal myocardial infarction was greatest in male patients with LDLR/PCSK9 gene variants compared with those with LDLR gene variant (86% versus 24%; P <0.001). Conclusions Patients with LDLR/PCSK9 gene variants were high‐risk genotype associated with atherogenic lipid profiles and worse cardiovascular outcomes. These findings underscore the importance of genetic testing to identify patients with LDLR/PCSK9 gene variants, who require more stringent antiatherosclerotic management.

Arbutin prevents alterations in mitochondrial and lysosomal enzymes in isoproterenol-induced myocardial infarction: An in vivo study

2020 ◽  
Vol 40 (1) ◽  
pp. 100-112
Author(s):  
S Sivasangari ◽  
L Asaikumar ◽  
L Vennila
Keyword(s):  
Myocardial Infarction ◽  
Lysosomal Enzymes ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Heart Tissue ◽  
Lipoprotein Cholesterol ◽  
Tissue Homogenate ◽  
Mitochondrial Enzymes ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol

The present study demonstrated the protective effects of arbutin (ARB) on hyperlipidemia, mitochondrial, and lysosomal membrane damage and on the DNA damage in rats with isoproterenol (ISO)-induced myocardial infarction (MI). Rats were pretreated with ARB (25 and 50 mg/kg body weight (bw)) for 21 days. After pretreatment with ARB, MI was induced by subcutaneous injection of ISO (60 mg/kg bw) for two consecutive days at an interval of 24 h. The levels of TC, TG, and FFA were increased and decreased the level of PL in the heart tissue of ISO-induced MI rats. Very-low-density lipoprotein cholesterol and low-density lipoprotein cholesterol were increased while high-density lipoprotein cholesterol was decreased in the plasma of ISO-administered rats. A heart mitochondrial fraction of the ISO rats showed a significant decrease in the activities of mitochondrial enzymes isocitrate dehydrogenase, α-ketoglutarate dehydrogenase, succinate dehydrogenase, and malate dehydrogenase. The activities of lysosomal enzymes (β-glucosidase, β-glucuronidase, α-galactosidase, β-galactosidase, cathepsin-B, and cathepsin-D) were increased significantly in the heart tissue homogenate of disease control rats. In ISO-induced MI, rat’s significant increase in the percentage of tail DNA and tail length, and a decrease in the level of head DNA were also observed. ARB administration to MI rats brought all these parameters to near normality, showing the protective effect of ARB against MI in rats. The results of this study demonstrated that the 50 mg/kg bw of ARB shows higher protection than 25 mg/kg bw against ISO-induced damage.

scholarly journals Visit-to-Visit Low-Density Lipoprotein Cholesterol Variability and Risk of Cardiovascular Outcomes

2015 ◽  
Vol 65 (15) ◽  
pp. 1539-1548 ◽  
Author(s):  
Sripal Bangalore ◽  
Andrei Breazna ◽  
David A. DeMicco ◽  
Chuan-Chuan Wun ◽  
Franz H. Messerli
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Cardiovascular Outcomes ◽  
Lipoprotein Cholesterol ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol

scholarly journals Effects of alirocumab on types of myocardial infarction: insights from the ODYSSEY OUTCOMES trial

2019 ◽  
Vol 40 (33) ◽  
pp. 2801-2809 ◽  
Author(s):  
Harvey D White ◽  
Ph Gabriel Steg ◽  
Michael Szarek ◽  
Deepak L Bhatt ◽  
Vera A Bittner ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Statin Therapy ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
Type 3 ◽  
Intensive Statin Therapy

Abstract Aims  The third Universal Definition of Myocardial Infarction (MI) Task Force classified MIs into five types: Type 1, spontaneous; Type 2, related to oxygen supply/demand imbalance; Type 3, fatal without ascertainment of cardiac biomarkers; Type 4, related to percutaneous coronary intervention; and Type 5, related to coronary artery bypass surgery. Low-density lipoprotein cholesterol (LDL-C) reduction with statins and proprotein convertase subtilisin–kexin Type 9 (PCSK9) inhibitors reduces risk of MI, but less is known about effects on types of MI. ODYSSEY OUTCOMES compared the PCSK9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome (ACS) and elevated LDL-C (≥1.8 mmol/L) despite intensive statin therapy. In a pre-specified analysis, we assessed the effects of alirocumab on types of MI. Methods and results  Median follow-up was 2.8 years. Myocardial infarction types were prospectively adjudicated and classified. Of 1860 total MIs, 1223 (65.8%) were adjudicated as Type 1, 386 (20.8%) as Type 2, and 244 (13.1%) as Type 4. Few events were Type 3 (n = 2) or Type 5 (n = 5). Alirocumab reduced first MIs [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77–0.95; P = 0.003], with reductions in both Type 1 (HR 0.87, 95% CI 0.77–0.99; P = 0.032) and Type 2 (0.77, 0.61–0.97; P = 0.025), but not Type 4 MI. Conclusion  After ACS, alirocumab added to intensive statin therapy favourably impacted on Type 1 and 2 MIs. The data indicate for the first time that a lipid-lowering therapy can attenuate the risk of Type 2 MI. Low-density lipoprotein cholesterol reduction below levels achievable with statins is an effective preventive strategy for both MI types.

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