Abstract 9793: Pcsk9 Loss-of-function Variants, Low-density Lipoprotein Cholesterol, and Risk of Coronary Heart Disease and Stroke: Data From the REGARDS Study and CHARGE Consortium

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Shia T Kent ◽  
Robert S Rosenson ◽  
Christy L Avery ◽  
Adolfo Correa ◽  
Steven R Cummings ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Association Studies ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Low Density ◽  
Loss Of Function ◽  
Low Density Lipoprotein Cholesterol ◽  
Regards Study

Introduction: PCSK9 loss-of-function variants are associated with reduced low-density lipoprotein cholesterol (LDL-C) concentrations. Genetic association studies of PCSK9 loss-of-function variants allow for the examination of the effects of lifetime low LDL-C on cardiovascular outcomes. Hypothesis: PCSK9 loss-of-function variants are associated with lower concentrations of LDL-C and reduced risk of coronary heart disease (CHD) and stroke. Methods: We studied the association of PCSK9 loss-of-function Y142X and C679X nonsense variants (n=366; 2.1%) in 17,459 African Americans (AAs) and R46L missense variants (n=962; 3.1%) in 31,469 whites with LDL-C, CHD and stroke in the US-based REasons for Geographic And Racial Difference in Stroke (REGARDS) study and 8 cohorts in the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. We combined multivariable adjusted differences in LDL-C between participants with and without PCSK9 variants across studies using inverse-variance weighted fixed-effects models. We calculated unadjusted odds ratios (ORs) for associations between PCSK9 variants and incident CHD (851 events in AAs and 2,662 events in whites) and stroke (523 events in AAs and 1,660 events in whites) using pooled Mantel-Haenszel estimates with continuity correction factors. Results: In the pooled cohorts, PCSK9 variants were associated with 36 mg/dL (95% confidence interval [CI]: 31, 40) lower LDL-C in AAs and 13 mg/dL (95% CI: 11, 16) lower LDL-C in whites. PCSK9 variants were associated with a pooled OR for CHD of 0.51 (95% CI: 0.28, 0.92) in AAs and 0.82 (95% CI: 0.63, 1.06) in whites. PCSK9 variants were not associated with incident stroke (OR=0.84 [95% CI: 0.48, 1.47] in AAs and OR=1.06 [95% CI: 0.80, 1.41] in whites). Conclusions: These results provide evidence that PCSK9 variants are associated with lifelong reduction in LDL-C and may lead to lower CHD risk, but no effect on stroke risk.

Management of persons with high risk of coronary heart disease but low serum low-density lipoprotein cholesterol

2003 ◽  
Vol 91 (9) ◽  
pp. 1134-1136 ◽  
Author(s):  
Christopher C. Case ◽  
Terry A. Jacobson ◽  
Susan Roberts ◽  
Ann Buckley ◽  
Kathleen M. Murtaugh ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
High Risk ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
Low Serum

scholarly journals Chronic pancreatitis in patients with coronary heart disease: a lipid spectrum of blood, a possibility of correction

2018 ◽  
Vol 41 (3) ◽  
pp. 31-39
Author(s):  
T. M. Hristich ◽  
D. O. Gontsariuk
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Chronic Pancreatitis ◽  
Total Cholesterol ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
Lipid Spectrum

Aim of research is to evaluate significance of changes in the lipid spectrum of blood in patients with chronic pancreatitis with coronary heart disease in the pathogenesis of the comorbidity of these diseases and in the dynamics of treatment with polycosanol. Materials and methods. The study was conducted in 22 patients (10 patients with chronic pancreatitis and dyslipidemia, 12 patients with comorbidity of chronic pancreatitis and coronary heart disease in CHD II-II A-B syndrome of stage II-III functional class) and in 10 almost healthy individuals. There were 13 men, 9 women, 31–69 years old. Patients of two groups in addition to protocol treatment were prescribed polycosanol 10 mg 1 time in the evening during dinner, up to 3 months. To study the characteristics of the lipid spectrum of the blood, the level of total cholesterol, high-density lipoprotein cholesterol, triglycerols was determined (using the Zlatix-Zack-based Lachema reagents (Czech Republic)). The level of low-density lipoprotein cholesterol was determined using the Friedewald calculation method, taking into account that the triglycerol concentration did not exceed 4.5 mmol/l. In addition, very low density lipoprotein cholesterol and an atherogenicity index were determined using conventional calculation methods. Results. In patients with a combined course of chronic pancreatitis with coronary heart disease, in most cases there is a significant (p<0.05) increase in total cholesterol, low and very low-density lipoproteins and triglycerols. When analyzing the types of dyslipidemia, it was found that ІІа and ІІв types were more common (22 і 25%, respectively), but with comorbidity ІІ and ІV type of dyslipidemia was more often detected. In the dynamics of a three-month treatment with polycosanol in patients with chronic pancreatitis, the cholesterol levels of high-density lipoproteins increased significantly and the triglycerol values ​​significantly decreased, indicating a hypolipidemic effect of the drug and the possibility of using it in combination with statins in order to reduce the risk of cardiovascular events. Conclusion. The comorbidity of chronic pancreatitis with ischemic heart disease increases the risk of progression of dyslipidemia and atherosclerosis. This is confirmed by an increased atherogenic index in this group of patients, along with the severity of lipid spectrum disorders. The addition of polycosanol to patients with chronic pancreatitis and dyslipidemia, as well as in combination with coronary heart disease, contributes to the reduction and normalization of certain parameters of the lipid spectrum of the blood. This allows us to recommend a drug for long-term treatment of these groups of patients, including in combination with statin therapy.

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