scholarly journals Trp Fluorescence Redshift during HDL Apolipoprotein Denaturation Is Increased in Patients with Coronary Syndrome in Acute Phase: A New Assay to Evaluate HDL Stability

2021 ◽  
Vol 22 (15) ◽  
pp. 7819
Author(s):  
Victoria López-Olmos ◽  
María Luna-Luna ◽  
Elizabeth Carreón-Torres ◽  
Héctor González-Pacheco ◽  
Rocío Bautista-Pérez ◽  
...  

High-density lipoproteins’ (HDL) stability is a determinant of their residence times in plasma and consequently an important parameter that influences the beneficial properties of these lipoproteins. Since there are no accessible procedures for this purpose, here, we describe the methodological conditions to assess the stability of the HDL based on the redshift of the fluorescence spectrum of tryptophans contained in the structure of HDL-apolipoproteins during incubation with urea 8M. Along the HDL denaturation kinetics, the main variations of fluorescence were observed at the wavelengths of 330, 344, and 365 nm at room temperature. Therefore, HDL denaturation was estimated using the tryptophan (Trp)-ratio of fluorescence intensity (rfi) at such wavelengths. By setting 100% of the measurable denaturation at 26 h, HDL reached 50% after 8 h of incubation with urea. Then, for further analyses we determined the percentage of HDL denaturation at 8 h as an estimation of the stability of these lipoproteins. To explore the potential usefulness of this test, we analyzed the stability of HDL isolated from the plasma of 24 patients diagnosed with acute coronary syndrome (ACS). These HDL presented significantly higher percentages of denaturation (64.9% (58.7–78.4)) than HDLs of healthy individuals (23.3% (20.3-27.0)). These results indicate that HDL in ACS are less stable than in control subjects. Moreover, the percentage of denaturation of HDL correlated with body mass index and aspartate transaminase plasma activity. Furthermore, apo-I, HDL-cholesterol, HDL-triglycerides, and apo A-I-to-triglycerides ratio correlated with the percentage of HDL denaturation, suggesting that the lipoprotein composition is a main determinant of HDL stability. Finally, the percentage of HDL denaturation is the parameter that predicted the presence of ACS as determined by a machine learning procedure and logistic regression analysis. In conclusion, we established the methodological conditions to assess the stability of HDL by a fluorescence-based method that merits exploration in prospective studies for evaluating the coronary artery disease risk.

Author(s):  
Pyry Helkkula ◽  
Tuomo Kiiskinen ◽  
Aki S. Havulinna ◽  
Juha Karjalainen ◽  
Seppo Koskinen ◽  
...  

AbstractProtein-truncating variants (PTVs) affecting dyslipidemia risk may point to therapeutic targets for cardiometabolic disease. Our objective was to identify PTVs that associated with both lipid levels and cardiometabolic disease risk and assess their possible associations with risks of other diseases. To achieve this aim, we leveraged the enrichment of PTVs in the Finnish population and tested the association of low-frequency PTVs in 1,209 genes with serum lipid levels in the Finrisk Study (n = 23,435). We then tested which of the lipid-associated PTVs also associated with risks of cardiometabolic diseases or 2,264 disease endpoints curated in the FinnGen Study (n = 176,899). Three PTVs were associated with both lipid levels and the risk of cardiometabolic disease: triglyceride-lowering variants in ANGPTL8 (−24.0[-30.4 to −16.9] mg/dL per rs760351239-T allele, P = 3.4× 10−9) and ANGPTL4 (−14.4[-18.6 to −9.8] mg/dL per rs746226153-G allele, P = 4.3 × 10−9) and the HDL cholesterol-elevating variant in LIPG (10.2[7.5 to 13.0] mg/dL per rs200435657-A allele, P = 5.0 × 10−13). The risk of type 2 diabetes was lower in carriers of ANGPTL8 (odds ratio [OR] = 0.67[0.47-0.92], P = 0.01), ANGPTL4 (OR = 0.70[0.60-0.82], P = 1.4× 10−5) and LIPG (OR = 0.67[0.48-0.91], P = 0.01) PTVs than in noncarriers. Moreover, the odds of coronary artery disease were 44% lower in carriers of a PTV in ANGPTL8 (OR = 0.56[0.38-0.83], P = 0.004). Finally, the phenome-wide scan of the ANGPTL8 PTV showed a markedly higher associated risk of esophagitis (585 cases, OR = 174.3[17.7-1715.1], P = 9.7 × 10−6) and sensorineural hearing loss (12,250 cases, OR = 2.45[1.63-3.68], P = 1.8 × 10−5). The ANGPTL8 PTV carriers were less likely to use statin therapy (53,518 cases, OR = 0.53[0.41-0.71], P = 1.2 × 10−5). Our findings provide genetic evidence of potential long-term efficacy and safety of therapeutic targeting of dyslipidemias.


2003 ◽  
Vol 42 (148) ◽  
Author(s):  
Man B KC ◽  
S Rajbhandari ◽  
D Sharma ◽  
R Malla ◽  
YR Limbu ◽  
...  

A total of 230 patients admitted in coronary care unit of Shahid Gangalal National Heart Centre in betweenNovember 2001 and October 2002 were studied. 157 (68.2%) were male, with mean age of 62.8±11.8 years.Majority of acute coronary syndrome (ACS) events were observed in males with advanced age (> 65 years).About 68% patients with ACS were smoker, the most common modifiable risk factor followed by hypertension,dyslipidaemia and diabetes. A strong trend towards development of coronary artery disease (CAD) wasfound in subjects with positive family history of CAD. Multiple risk factors (2 or more) were present in vastmajority of patients. Modifiable risk factors, with smoking at number one position are more common inacute coronary syndrome patients. Appropriate management of modifiable risk factors is advisable to reducethe incidence of coronary artery disease.Key Words: Coronary Artery Disease, Risk Factors.


BMJ Open ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. e038868
Author(s):  
Amy Bailey ◽  
Rosemary Korda ◽  
Jason Agostino ◽  
Tony Stanton ◽  
Gabriela Kelly ◽  
...  

ObjectivesTo describe (1) absolute cardiovascular disease risk (ACVDR) scores in patients presenting to hospital with acute coronary syndrome (ACS) and (2) proportions of these patients on guideline-recommended pharmacotherapy according to their ACVDR score.DesignCross-sectional study.SettingSingle-site tertiary centre hospital, Queensland, Australia over a 12-month period.ParticipantsPatients >18 years of age presenting to hospital with ACS due to coronary artery disease (CAD) confirmed by angiography.Primary and secondary outcome measuresProportion of patients without prior history of CVD with a high ACVDR score, and of patients with a prior history of CVD, who are on guideline-recommended pharmacotherapy.Results527 ACS patients were included of whom the mean age was 63 years and 75% were male. Overall, 66% (350) had no prior CVD and 34% (177) patients had prior CVD.In patients with no prior CVD, the proportions of patients with low, intermediate and high CVD risk scores were 41%, 24% and 36%. In the no prior CVD, high-risk patient group, 48% were on no preventative pharmacotherapy, 32% on single pharmacotherapy and 20% patients on complete guideline-recommended pharmacotherapy. In the prior CVD group, 7% patients were on no pharmacotherapy, 40% on incomplete pharmacotherapy and 53% were on complete guideline-recommended pharmacotherapy.ConclusionThis study adds to the evidence on implementation gaps in guideline-recommended management of ACVDR, showing that a large proportion of patients presenting with ACS due to CAD were at high risk of developing CVD prior to the event and most were not on guideline-recommended treatment. A significant proportion of these events are likely to have been preventable, and therefore, increased assessment and appropriate treatment of ACVDR in primary care is needed to reduce the incidence of CVD events in the population.


2017 ◽  
Vol 24 (01) ◽  
pp. 26-30
Author(s):  
Ahmed Zeeshan ◽  
Zaheer Ahmad ◽  
Ghulam Abbas Tahir ◽  
Yasir Yaqoob

Microalbuminuria is a strong and independent indicator of increased cardiovascularrisk among individuals with and without diabetes and hypertension. The pathophysiologicmechanism underlying the association between albumin excretion and cardiovascular disease(CVD) is that microalbuminuria can be a predictor of CVD risk as it reflects the vascular damagein kidneys. It also shows endothelial damage predicting CV disease risk. Based on this theory,periodic screening for microalbuminuria could allow early identification of vascular diseaseand help stratify overall cardiovascular risk, especially in patients with risk factors such ashypertension or diabetes. Therefore microalbuminuria can be used for stratification of risk forcardiovascular disease. Once microalbuminuria is present, cardiovascular risk factor reductionshould be aggressive. Objectives: The objective of the study was to determine the role ofmicroalbuminuria as an atherosclerotic risk factor and its association with coronary arterydisease. Study Design: Cross-sectional study. Duration of Study: Duration of study was6 months with first patient enrolled on 16-03-2007 and last patient enrolled on 15-09-2007.Setting: Medical Unit-III and CCU Allied Hospital, Faisalabad. Subjects: 300 patients withacute coronary syndrome, admitted in Allied hospital Faisalabad were enrolled. Methods: 300patients diagnosed as having acute coronary syndrome admitted in Allied hospital Faisalabad,were included in the study. Early morning urine as well as 24 hour urine had been collectedin sterilized urine bags and microalbuminuria was tested. Results: In this study 300 patientshaving acute coronary syndrome were enrolled. Microalbuminuria was positive in 66 (22%)patients and 234 (78%) patients had no microalbuminuria. There was significant associationbetween microalbuminuria and atherosclerotic coronary artery disease. Conclusion: It isconcluded that microalbuminuria is an atherosclerotic risk factor and it is strongly associatedwith coronary artery disease.


2003 ◽  
Vol 228 (4) ◽  
pp. 434-440 ◽  
Author(s):  
William J. Banz ◽  
Margaret A. Maher ◽  
Warren G. Thompson ◽  
David R. Bassett ◽  
Wayne Moore ◽  
...  

Individuals exhibiting “the metabolic syndrome” have multiple coronary artery disease risk factors, including insulin resistance, hyperlipidemia, hypertension, and android obesity. We performed a randomized trial to compare the effects of aerobic and resistance training regimens on coronary risk factors. Twenty-six volunteers who exhibited android obesity and at least one other risk factor for coronary artery disease were randomized to aerobic or resistance training groups. Body mass index, waist-to-hip ratio, glucose, insulin, body composition, 24-hr urinary albumin, fibrinogen, blood pressure, and lipid profile were measured at baseline and after 10 weeks of exercise training. Both groups showed a significant reduction in waist-to-hip ratio and the resistance training group also showed a reduction in total body fat. There was no significant change in mean arterial blood pressure in either group. Fasting plasma glucose, insulin, total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides were unchanged in both groups. High-density lipoprotein (HDL) cholesterol increased (13%) with aerobic training only. Plasma fibrinogen was increased (28% and 34%, P < 0.02) in both groups and both groups showed a significant decrease (34% and 28%, P < 0.03) in microalbuminuria after their respective training regimen. In conclusion, resistance training was effective in improving body composition of middle-aged obese sedentary males. Only aerobic training was effective in raising HDL cholesterol. More studies are warranted to assess the effects of exercise on plasma fibrinogen and microalbuminuria.


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