Effect of Evolocumab on Lipoprotein(a) and PCSK9 in Healthy Individuals with Elevated Lipoprotein(a) Level

Background and aims: The aim of this study was to investigate the influence of a single injection of Evolocumab on the dynamics of Lp(a), fractions of apoB100-containing lipoproteins, PCSK9, and their complexes in healthy individuals with elevated Lp(a) levels. Methods: This open-label, 4-week clinical study involved 10 statin-naive volunteers with Lp(a) >30 mg/dL, LDL-C < 4.9 mmol/L, and a moderate risk of cardiovascular events. The concentrations of Lp(a), lipids, PCSK9, circulating immune complexes (CIC), and plasma complexes of PCSK9 with apoB100-containing lipoproteins (Lp(a)–PCSK9 and LDL–PCSK9) were measured before and each week after Evolocumab (MABs) administration. Results: After a single dose injection of 140 mg of MABs, the median concentration of PCSK9 in serum increased from 496 to 3944 ng/mL; however, the entire pool of circulating PCSK9 remained bound with MABs for 2–3 weeks. LDL-C level decreased significantly from 3.36 mmol/L to 2.27 mmol/L during the first two weeks after the injection. Lp(a) concentrations demonstrated multidirectional changes in different patients with the maximal decrease on the second week. There were no positive correlations between the changes in levels of Lp(a), LDL-C, and TC. The change in the amount of circulating complex of PCSK9–Lp(a) was significantly less than of PCSK9–apoB100 (−5% and −47% after 1 week, respectively). Conclusions: A single administration of monoclonal antibodies against PCSK9 (Evolocumab) in healthy individuals with hyperlipoproteinemia(a) resulted in a decrease of Lp(a) of 14%, a 5% decrease in PCSK9–Lp(a), a 36% reduction of LDL-C, a 47% decrease in PCSK9–apoB100 and a tenfold increase in total serum PCSK9 concentration.

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Impact of cardiovascular health status on the association between changes in physical activity and major cardiovascular events and mortality among 88,320 adults: outcomes of the Lifelines Cohort Study

European Journal of Preventive Cardiology ◽

10.1093/eurjpc/zwab061.191 ◽

2021 ◽

Vol 28 (Supplement_1) ◽

Author(s):

EA Bakker ◽

DC Lee ◽

MTE Hopman ◽

DHJ Thijssen ◽

TMH Eijsvogels

Keyword(s):

Cardiovascular Events ◽

Cardiovascular Health ◽

Large Reduction ◽

Healthy Individuals ◽

Moderate Improvement ◽

Moderate Reduction ◽

Lower Baseline ◽

All Cause Mortality ◽

The Impact ◽

Large Improvement

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): The Lifelines Biobank initiative received funding from the Dutch Ministry of Health, Welfare and Sport, the Dutch Ministry of Economic Affairs, the University Medical Center Groningen [UMCG], University Groningen and the Northern Provinces of the Netherlands. The work of T.M.H.E is supported by the Netherlands Heart Foundation [Senior E-Dekker grant #2017T051]. Background. Regular physical activity (PA) improves health. Many observational studies investigated the association between PA and health at a single time-point, but PA might change over time. Purpose. To examine the association between change in PA and major adverse cardiovascular events (MACE) and all-cause mortality, and to investigate the impact of cardiovascular health status at baseline on these outcomes. Methods. This study used data from the Lifelines Cohort Study (N = 88,320). Self-reported PA volumes were presented as Metabolic Equivalent of Task (MET) min/week. Change in PA was calculated by subtracting MET-min/week at the first assessment from the second assessment (median interval: 4 yrs), and 5 groups were created; large reduction (< -1500), moderate reduction (-1500 to -250), no change (-250 to 250), moderate improvement (-250 to 250) and large improvement (>1500). The outcome was a combination of MACE and all-cause mortality. Results. During a median follow-up of 7 years, 667 events occurred among healthy individuals (43 ± 12 yrs, 1% of 69,818) and 599 in individuals with CVRF (55 ± 11 yrs, 3% of 18,502). Adjusted for confounders and baseline PA, healthy individuals with a large reduction in PA had a greater risk of incident MACE and mortality (Table). In CVRF, moderate to large improvements in PA were associated with reductions in adverse outcomes. Risk estimates became stronger in individuals with lower baseline PA (<2000 MET-min/week), Table). Conclusions. Maintaining PA in healthy individuals and increasing PA in individuals with CVRF over time is important to prevent MACE and mortality. The impact of changes in PA was stronger for individuals with lower baseline PA. Table. Change of PA, MACE and mortality. Changes in PA Healthy CVRF Large reduction 1.40 [1.02;1.93] 1.27 [0.95;1.70] Moderate reduction 1.22 [0.89;1.68] 0.97 [0.72;1.30] No changes Ref Ref Moderate improvement 1.04 [0.74;1.44] 0.65 [0.47;0.91] Large improvement 0.96 [0.71;1.31] 0.69 [0.51; 0.94] Individuals with lower baseline PA Large reduction 2.24 [0.96;5.21] 2.85 [1.44;5.63] Moderate reduction 1.77 [1.10;2.84] 1.33 [0.89;1.98] No changes Ref Ref Moderate improvement 1.16 [0.73;1.83] 0.49 [0.31;0.76] Large improvement 0.77 [0.48;1.23] 0.58 [0.39;0.86]

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Lipoprotein(a) and Cardiovascular Outcomes after Revascularization of Carotid and Lower Limbs Arteries

Biomolecules ◽

10.3390/biom11020257 ◽

2021 ◽

Vol 11 (2) ◽

pp. 257

Author(s):

Marat V. Ezhov ◽

Narek A. Tmoyan ◽

Olga I. Afanasieva ◽

Marina I. Afanasieva ◽

Sergei N. Pokrovsky

Keyword(s):

Primary Endpoint ◽

Cardiovascular Events ◽

Cardiovascular Outcomes ◽

Lower Limbs ◽

Lipid Lowering ◽

Lipid Lowering Therapy ◽

Cox Regression Analysis ◽

Lipoprotein A ◽

Secondary Endpoints

Background: Despite high-intensity lipid-lowering therapy, there is a residual risk of cardiovascular events that could be associated with lipoprotein(a) (Lp(a)). It has been shown that there is an association between elevated Lp(a) level and cardiovascular outcomes in patients with coronary heart disease. Data about the role of Lp(a) in the development of cardiovascular events after peripheral revascularization are scarce. Purpose: To evaluate the relationship of Lp(a) level with cardiovascular outcomes after revascularization of carotid and lower limbs arteries. Methods: The study included 258 patients (209 men, mean age 67 years) with severe carotid and/or lower extremity artery disease, who underwent successful elective peripheral revascularization. The primary endpoint was the composite of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. The secondary endpoint was the composite of primary endpoint and repeated revascularization. Results: For 36-month follow-up, 29 (11%) primary and 128 (50%) secondary endpoints were registered. There was a greater risk of primary (21 (8%) vs. 8 (3%); hazard ratio (HR), 3.0; 95% confidence interval (CI) 1.5–6.3; p < 0.01) and secondary endpoints (83 (32%) vs. 45 (17%), HR, 2.8; 95% CI 2.0–4.0; p < 0.01) in patients with elevated Lp(a) level (≥30 mg/dL) compared to patients with Lp(a) < 30 mg/dL. Multivariable-adjusted Cox regression analysis revealed that Lp(a) was independently associated with the incidence of cardiovascular outcomes. Conclusions: Patients with peripheral artery diseases have a high risk of cardiovascular events. Lp(a) level above 30 mg/dL is significantly and independently associated with cardiovascular events during 3-year follow-up after revascularization of carotid and lower limbs arteries.

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381-P: Type 2 Diabetes Significantly Modulates the Power of Lipoprotein(a) to Predict Cardiovascular Events and Mortality in Young Coronary Artery Disease Patients

Diabetes ◽

10.2337/db21-381-p ◽

2021 ◽

Vol 70 (Supplement 1) ◽

pp. 381-P

Author(s):

ARTHUR MADER ◽

MAXIMILIAN MAECHLER ◽

BARBARA LARCHER ◽

LUKAS SPRENGER ◽

BEATRIX MUTSCHLECHNER ◽

...

Keyword(s):

Type 2 Diabetes ◽

Coronary Artery Disease ◽

Coronary Artery ◽

Cardiovascular Events ◽

Lipoprotein A ◽

Artery Disease ◽

P Type

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Cardiac Health Indicators in Critical COVID-19 Cases

Recent Advances in Biology and Medicine ◽

10.18639/rabm.2021.1426420 ◽

2021 ◽

Vol 7 (1) ◽

pp. 1-6

Author(s):

Sultan Alasmari ◽

Mohammed Makkawi ◽

Mutaib M Mashraqi ◽

Saleh Alqahtani ◽

Mustafa Alqahtani ◽

...

Keyword(s):

Creatine Phosphokinase ◽

Health Indicators ◽

Total Serum ◽

Healthy Individuals ◽

Icu Patients ◽

Cardiac Health ◽

Serum Creatine Phosphokinase ◽

Global Concern ◽

Asir Region ◽

The Impact

Coronavirus disease-2019 (COVID-19) is an infectious disease that has spread worldwide and led to ongoing global concern. The pandemic prompted researchers to examine the impact of COVID-19 on human organs. The heart is one such organ. This study investigates the possible prediction of heart condition using some biochemical markers of particularly critically ill patients referred to an intensive care unit (ICU). Results of various serum biomarkers of patients infected with COVID-19 receiving treatment in the ICU, Asir Central Hospital, Asir Region, Saudi Arabia, were extracted and compared with healthy individuals using the Mann-Whitney U test. The study showed a distinguished increase in total Serum creatine phosphokinase-Total (CPK-Total), Serum creatine phosphokinase-MP (CPK-MP) levels among COVID-19/ICU patients. But, this increase was not statistically significant. Besides, aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase levels revealed a statistically significant increase in the infected group compared with controls. Examination of electrolytes showed a reduction in calcium median value in COVID-19/ICU patients. Data revealed a possible influence of COVID-19 on the heart. Herein, we observe significant parameters that may reflect cardiovascular injury elicited by the virus. These biomarkers possibly used to monitor the severity of disease on the cardiovascular system.

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Malondialdehyde Assay in the Evaluation of Aspirin Antiplatelet Effects

Pharmacology ◽

10.1159/000493754 ◽

2018 ◽

Vol 103 (1-2) ◽

pp. 23-29 ◽

Cited By ~ 1

Author(s):

Amin Polzin ◽

Lisa Dannenberg ◽

Theresa Schneider ◽

Betül Knoop ◽

David Naguib ◽

...

Keyword(s):

Cardiovascular Events ◽

Operating Characteristic ◽

Light Transmission ◽

Platelet Reactivity ◽

Area Under The Curve ◽

Healthy Individuals ◽

Antibody Assay ◽

Light Transmission Aggregometry ◽

Artery Disease

Aspirin is essential in secondary prevention of patients after myocardial infarction and with coronary artery disease. However, impaired pharmacodynamic response to aspirin is frequent (high on-treatment platelet reactivity [HTPR]). This leads to an enhanced prevalence of cardiovascular events and to an impaired clinical outcome. The current specific assays to evaluate aspirin antiplatelet effects are complex, time-consuming and demand for a high laboratory expertise. Therefore, we developed a potentially bedside assay based on the determination of malondialdehyde (MDA). MDA is a by-product of the thromboxane (TX) formation, which is synthesized in equimolar concentrations. In this study, we compared this MDA assay to the conventional assays in determination of pharmacodynamic aspirin response. For this, aspirin antiplatelet effects were measured in 22 healthy individuals and 63 aspirin treated patients using TX B2 formation enzyme-linked antibody assay, arachidonic acid induced light transmission aggregometry (LTA) and the new fluorometric MDA assay. In patients, MDA levels correlated well with TX formation (R = 0.81; 95% CI 0.69–0.88; p < 0.001) and LTA (R = 0.84; CI 0.74–0.91; p < 0.001). Receiver operating characteristic analyses revealed that the MDA assay does detect HTPR to aspirin sufficiently (area under the curve: 0.965; p < 0.001). The optimal cut-off was > 128 nmol/L (sensitivity of 100%, specificity of 91%). The new MDA assay is reliable in detecting HTPR. It is highly specific in the evaluation of antiplatelet effects by aspirin. This promising and potential bedside assay needs to be evaluated in clinical practice.

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Bioequivalence of Two Oral Tablet Formulations of Betahistine 24 Mg: Single-Dose, Open-Label, Randomized, Two-Period Crossover Comparison in Healthy Individuals

Journal of Bioequivalence & Bioavailability ◽

10.4172/jbb.1000207 ◽

2015 ◽

Vol 07 (01) ◽

Author(s):

Larisa Estrada Beatriz Cedillo

Keyword(s):

Single Dose ◽

Healthy Individuals ◽

Open Label ◽

Oral Tablet ◽

Tablet Formulations ◽

Crossover Comparison

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A brief reflection on the role of cholesterol in psychopathology among female psychiatric patients

Acta Marisiensis - Seria Medica ◽

10.2478/amma-2021-0015 ◽

2021 ◽

Vol 67 (2) ◽

pp. 102-107

Author(s):

Edina Dimeny ◽

Erika Bán ◽

Attila Brassai

Keyword(s):

Risk Factors ◽

Cholesterol Level ◽

Suicide Risk ◽

Psychiatric Patients ◽

Blood Cholesterol ◽

Total Serum ◽

Risk Category ◽

Moderate Risk ◽

Cholesterol Levels ◽

Suicide Behavior

Abstract Objective: Cholesterol is one of the cardiovascular risk factors, but also a core component of the central nervous system. Moreover, hyper-cholesterolemia and hypocholesterolemia are directly related to numerous mental illnesses too. This study intents to examine the association between cholesterol level and autolytic behavior among female psychiatric patients. Methods: The present study involves 123 female subjects, who suffered from suicidal thoughts at the moment of hospitalization. The risk of suicidal intentions was assessed by the Modified Scale for Suicide Ideation (Miller et al) and their total serum cholesterol levels were measured. We performed a case-control, analytical, randomized, observational study at the Clinical Hospital of Neurology and Psychiatry Brasov among adult female psychiatric patients admitted during 2014. Results: By our results we distinguished 3 categories: 38 patients with low suicide risk, 32 with moderate risk and 53 with high suicide risk. Significant difference can be noticed in the higher suicide risk patients’ blood cholesterol levels: 44 patients having under 4,5mmol/L total cholesterol level (83%). Although, in other two categories, this proportion is minimal: in the moderate-risk category were 8 patients, representing just 25 %, and in the low-risk category only 1 patient had her cholesterol level under 4,5mmol/L (2,6%). Conclusions: According to our results, proposing cholesterol-level as a biomarker for the determination of high-risk suicide behavior can be important. The presence of other important risk factors (sociodemographic and psychiatric variables) can increase exponentially the suicide behavior. The limitations of this study are the relatively small number of cases and the lack of longitudinal subsequent follow-up. Further investigations are needed on a larger and more heterogenous sample of patients in order to clarify this suggestive correlation.

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Correction to: Elevated Lp(a) (Lipoprotein[a]) Levels Increase Risk of 30-Day Major Adverse Cardiovascular Events in Patients Following Carotid Endarterectomy

Stroke ◽

10.1161/str.0000000000000353 ◽

2020 ◽

Vol 51 (12) ◽

Keyword(s):

Carotid Endarterectomy ◽

Cardiovascular Events ◽

Major Adverse Cardiovascular Events ◽

Lipoprotein A ◽

Increase Risk

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Abstract P431: ASSOCIATION OF LIPOPROTEIN(A) WITH CARDIOVASCULAR EVENTS IN YOUNG NON-FAMILIAL HYPERCHOLESTEROLEMIA

Circulation ◽

10.1161/circ.141.suppl_1.p431 ◽

2020 ◽

Vol 141 (Suppl_1) ◽

Author(s):

Pao-Hsien Chu

Keyword(s):

Cardiovascular Disease ◽

Coronary Artery Disease ◽

Coronary Artery ◽

Fatty Liver ◽

Familial Hypercholesterolemia ◽

Cardiovascular Events ◽

Healthy Population ◽

Lipoprotein A ◽

A Value ◽

Artery Disease

Background and aims: Elevated lipoprotein(a) is an independent risk factor for atherosclerotic cardiovascular disease especially in familial hypercholesterolemia. The association of elevated lipoprotein(a) within non-familial hypercholesterolemia or healthy population however, is not known. Therefore, we investigated the associations between elevated lipoprotein(a) and the risk of cardiovascular disease in a non-familial hypercholesterolemia clinically healthy young age cohort. Methods: In this retrospective cohort study, we reviewed medical records of 3,427 participants with lipoprotein(a) levels from a tertiary healthcare center in Taiwan. We further classified lipoprotein(a) level into four groups and analyzed cardiovascular events. Results: Our study population had a mean age 46 years old that were 78% male. Mean total cholesterol and low-density lipoprotein level were 195 mg/dL and 118 mg/dL respectively. Overall, 12.9% of the participants had an elevated lipoprotein(a) level (>30 mg/dL), and 2.7% had a very high level (>70 mg/dL). Thirty-three events including 6 participants with stroke and 27 with coronary artery disease were identified. A lipoprotein(a) level >70 mg/dL was associated with a higher risk of coronary artery disease events in Kaplan-Meier analysis. Aging was associated with a higher lipoprotein(a) value in the male participants but not in the female participants. However, the severity of fatty liver was not positively associated with lipoprotein(a) value. Conclusions: Elevated lipoprotein(a) was associated with coronary events but not the severity of fatty liver disease in non-familial hypercholesterolemia clinically healthy population. Aging may be associated with a higher lipoprotein(a) level in males but not females.

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