Residual Cholesterol Research Articles

The relationship between residual cholesterol risk and plaque characteristics in patients with acute coronary syndrome: Insights from an optical coherence tomography study

Background and aimsThe impact of residual cholesterol risk (RCR) on plaque characteristics is not fully understood. The study aims to explore the relationship between RCR and plaque features in patients presenting with acute coronary syndrome (ACS). MethodsAll ACS patients undergoing pre-intervention optical coherence tomography (OCT) with high-sensitivity C-reactive protein (hs-CRP) <2 mg/L on admission were retrospectively enrolled from January to December 2017, at Beijing Anzhen Hospital, Capital Medical University. RCR was defined as low density lipoprotein cholesterol (LDL-C) ≥1.8 mmol/L. Patients were divided into the RCR and non-RCR groups according to baseline LDL-C. ResultsA total of 90 patients (94 vessels) were included, with 50 in the RCR group and 40 in the non-RCR group, respectively. Compared with the non-RCR group, patients in the RCR group were younger (54.0 ± 11.04 vs. 58.4 ± 9.59, p = 0.049) and had a higher incidence of multivessel disease (6.0% vs. 2.5%, p = 0.028). With regard to plaque characteristics, fibrous plaque (0.0% vs 12.5%, p = 0.003) was less and fibroatheroma (79.6% vs. 50.0%, p = 0.028) was more frequently seen in the RCR group. Patients in the RCR group were more prone to present with plaque rupture (24.1% vs 5.0%, p = 0.008). Cholesterol crystal (22.2% vs 12.5%, p = 0.226) and thin-cap fibroatheroma (25.9% vs. 12.5%, p = 0.109) were more common in the RCR group, though without statistical difference. Multivariate logistic regression showed that RCR (odds ratio [OR]: 7.95, p = 0.011) and smoking (OR: 4.08, p = 0.026) were independent risk factors of plaque rupture in our patients. ConclusionsACS patients with RCR are more likely to have atherosclerotic plaque and plaque rupture, indicating a more vulnerable plaque phenotype.

Abstract 15567: Residual Cholesterol and Cardiovascular Events in Patients With Coronary Artery Disease Under Different Glucose Metabolism Status

Introduction: The atherogenicity of residual cholesterol (RC) has been underlined by recent guidelines, which was linked to coronary artery disease (CAD), especially for patients with diabetes mellitus (DM). Hypothesis: This study aimed to examine the prognostic value of plasma RC, clinically presented as triglyceride-rich lipoprotein-cholesterol (TRL-C) or remnant-like lipoprotein particles-cholesterol (RLP-C), in CAD patients with different glucose metabolism status. Methods: Fasting plasma TRL-C and RLP-C levels were directly calculated or measured in 4331 patients with CAD. Patients were followed for incident MACEs for up to 8.6 years and categorized according to both glucose metabolism status [DM, pre-DM, normal glycaemia regulation (NGR)] and RC levels. Cox proportional hazards model was used to calculate hazard ratios (HRs) with 95% confidence intervals. Results: During a mean follow-up of 5.1 years, 541 (12.5%) MACEs occurred. The risk for MACEs was significantly higher in patients with elevated RC levels after adjustment for potential confounders. No significant difference in MACEs was observed between pre-DM and NGR groups (p&gt;0.05). When stratified by status of glucose metabolism and RC levels, highest levels of RLP-C, calculated and measured TRL-C were significant and independent predictors of developing MACEs in pre-DM (HR: 2.10, 1.98, 1.92, respectively; all p&lt;0.05) and DM (HR: 2.25, 2.00, 2.16, respectively; all p&lt;0.05). Conclusions: In this large cohort study with long-term follow-up, data firstly demonstrated that higher RC levels were significantly associated with the worse prognosis in DM and pre-DM patients with CAD, suggesting RC might be a target for patients with impaired glucose metabolism.

The relationship between residual cholesterol risk and plaque characteristics in patients with acute coronary syndrome evaluated by optical coherence tomography

Abstract Background It has been demonstrated that high sensitive-C reactive protein (hs-CRP) and low density lipoprotein cholesterol (LDL-C) are independently associated with major adverse cardiovascular events (MACEs). Whether the level of LDL has impact on plaque characteristics in acute coronary syndrome (ACS) patients with normal hs-CRP are still unknown. Methods We retrospectively enrolled ACS patients with the level of hs-CRP&amp;lt;2mg/L on admission from 1st January, 2017 to 31st December,2017, from our hospital. All patients underwent pre-intervention optical coherence tomography (OCT) to evaluate the plaque characteristics. Residual cholesterol risk (RCR) was defined as LDL-C≥1.8mmol/L, while hs-CRP&amp;lt;2mg/L. According to the level of baseline LDL-C, patients were divided into RCR group and non-RCR group. Results A total of 90 patients (94 vessels) were included, with 50 patients in RCR group and 40 patients in non-RCR group. Compared with non-RCR group, patients in RCR group had higher levels of total cholesterol (4.39±0.89 vs 3.05±0.48, p=0.000), LDL-C (2.56±0.57 vs 1.54±0.22, p=0.000), triglycerides (1.11±1.12 vs 1.02±0.74, p=0.003). Patients in RCR group were younger (54.0±11.04 vs 58.4±9.59, p=0.049) and had higher rate of multivessel disease (6.0% vs 2.5%, p=0.028) than those in non-RCR group. With regard to plaque characteristics, fibrous plaque (0.0% vs 12.5%, p=0.003) was less seen and atherosclerotic plaque (79.6% vs 50.0%, p=0.028) was more seen in RCR group. In addition, patients in RCR group had significantly higher rate of plaque rupture than that in non-RCR group (24.1% vs 5%, p=0.008). To be noticed, cholesterol crystal and thin-cap fibroatheroma (TCFA) were more commonly in RCR group, though the difference was not statistical. Conclusion Patients with RCR have a great extent of plaque rupture, indicating more vulnerable plaque phenotype. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): China Youth Clinical Research Foundation-VG Foundation

Prognostic impact of elevated baseline CRP levels in primary PCI-treated patients with residual cholesterol risk

Abstract Background Recent large randomized studies have indicated the potential of anti-inflammatory therapies to reduce adverse cardiovascular events in patients with myocardial infarction, with the most pronounced benefit in patients with baseline elevated C-reactive protein (CRP). Purpose Our aim was to assess the association of CRP levels with 30-day and 1-year mortality in patients with acute myocardial infarction treated with primary PCI and with residual cholesterol risk. Methods The study included 1531 patients admitted for primary PCI, with the residual cholesterol risk, i.e. low-density lipoprotein cholesterol (LDL-C) levels of &amp;gt;1.80 mmol/l (70 mg/dl), from a prospectively kept electronic registry of a high-volume tertiary center, for whom in-hospital CRP measurements were available. Elevated CRP was defined as ≥5 mg/l (local laboratory cut off value), measured during index hospitalization. Cox regression models were constructed to assess the impact of elevated CRP on 30-day and 1-year mortality. Results 72% of the included patients with LDL-C &amp;gt;1.80 mmol/l had elevated in-hospital CRP (n=1107). Compared with patients with CRP levels within reference limit, elevated CRP was associated with older age (62 vs. 60, p&amp;lt;0.001), higher rates of diabetes (25.8% vs. 18.5%, p=0.002), renal failure (6.4% vs. 2.1%, p&amp;lt;0.001) and Killip class &amp;gt;1 at presentation (22.5% vs. 12.3%, p&amp;lt;0.001), as well as lower EF (44% vs. 48%, p&amp;lt;0.001) and lower haemoglobin on admission (13.9 g/dl vs. 14.2 g/dl, p&amp;lt;0.001). Crude mortality rates were increased in patients with CRP ≥5mg/l at both 30 days (6.0% vs. 2.4%, p=0.003) and 1 year (13.2% vs. 6.3%, p&amp;lt;0.001) (Figure). After adjusting for the observed baseline differences, CRP ≥5mg/l remained an independent predictor of mortality at 1 year (HR 1.691, 95% CI: 1.050–2.724, p=0.03), but not at 30 days (HR 1.690, 95% CI: 0.859–3.324, p=0.13). Conclusion In primary PCI-treated patients with residual cholesterol risk, elevated in-hospital CRP was independently associated with 1-year mortality. Our findings may thus suggest a potential window of opportunity, for anti-inflammatory therapies to improve outcomes beyond the acute phase. Figure 1 Funding Acknowledgement Type of funding source: None

From CANTOS to CIRT to COLCOT to Clinic: Will All Atherosclerosis Patients Soon Be Treated With Combination Lipid-Lowering and Inflammation-Inhibiting Agents?

From CANTOS to CIRT to COLCOT to Clinic: Will All Atherosclerosis Patients Soon Be Treated With Combination Lipid-Lowering and Inflammation-Inhibiting Agents?

Strategies to Overcome Residual Risk During Statins Era.

At present, atherosclerosis is one of the most important field in clinical and research medicine. Because it is closely related to cardiovascular (CV) and endocrine disorders such as coronary artery disease, cardiometabolic disorders, much research on how to manage atherosclerosis has been performed. The low-density lipoprotein cholesterol (LDL-C) concentration has been established as an independent risk factor for developing atherosclerosis, and considerable effort has been committed to educating both physicians and the general public on the importance of lowering LDL-C with statins. Although statins have already significantly improved CV outcomes, patients with LDL-C target levels achieved by intense statin therapy still have significant remaining CV risk. Statins already play a central role in managing hyperlipidemia; however, residual risk with statins is an important field of managing remaining CV risk. Recent studies have suggested residual cholesterol and inflammation risks in causing CV events. In the current review, we will discuss residual risk and suggest strategies to overcome it in the statins era.

Temporal Trends in Statin Prescriptions and Residual Cholesterol Risk in Patients With Stable Coronary Artery Disease Undergoing Percutaneous Coronary Intervention

Intensive low-density lipoprotein cholesterol (LDL-C) reduction with statins is recommended after elective percutaneous coronary intervention (PCI). We aimed to evaluate adherence to guideline-recommended statin therapy (GRST) and the rate of residual cholesterol risk (RCR) at follow-up after elective PCI. All patients who underwent elective PCI between January 2010 and May 2016 were prospectively included in this single-center study. GRST was defined as high-intensity statin (HIS) therapy for patients ≤75 years old and moderate-intensity statin (MIS) or HIS therapy for patients >75 years. RCR at follow-up was defined as <50% decrease in LDL-C with HIS or <30% with MIS for statin-naïve patients and as LDL-C >70 mg/dL for nonstatin-naïve patients. A total of 2,653 patients were included, with 1,304 (49.2%) discharged with GRST. There was a significant increase in the number of patients discharged with GRST over time from 44.2% in 2010 to 63.0% in 2016 (p <0.001). Conversely, RCR at follow-up was present in 1,120 patients (42.2%) overall and remained stable over time. Risk factors of RCR at follow-up were female gender (odds ratio [OR]: 1.38; 95% confidence interval [CI] 1.13 to 1.70), previous myocardial infarction (OR: 1.37; 95% CI 1.12 to 1.64), smoking (OR: 1.30; 95% CI 1.01 to 1.67), higher LDL-C level at baseline (OR: 1.22; 95% CI 1.18 to 1.25). The presence of RCR was associated with an increased adjusted risk of death within 1 year of the second LDL-C measurement (adjHR: 2.78; 95% CI 1.15 to 6.67). In conclusion, although the rate of GRST at discharge has improved significantly over time in patients who underwent elective PCI, the prevalence of RCR at follow-up has not changed appreciably suggesting that further implementation of guidelines as well as novel or more intensive pharmacotherapy may be warranted.

Pharmacological Strategies beyond Statins: Ezetimibe and PCSK9 Inhibitors.

Dyslipidemia, highly elevated, low-density lipoprotein (LDL) cholesterol, is a major cardiovascular risk factor. Statins have been proven to effectively reduce the risk of atherosclerotic cardiovascular disease (ASCVD) and are recommended as a first-line therapy for the primary and secondary prevention of ASCVD. However, statins may not be sufficient in decreasing LDL cholesterol levels and pose a significant on-treatment residual risk of major cardiovascular events (i.e., residual cholesterol risk) according to meta-analyses of statin trials. Current guidelines for cholesterol management to achieve additional LDL cholesterol reduction and reduce ASCVD risk recommend two hyperlipidemic agents besides statins. Use of ezetimibe, a cholesterol absorption inhibitor, leads to additional LCL cholesterol reduction and decreased ASCVD risk, when added to statin therapy, without raising significant safety concerns. Furthermore, in combination with a mild-to-moderate statin intensity, ezetimibe is used in situations of statin-associated adverse effects such as myalgia and the combination therapy is relatively safer. Monoclonal antibody of proprotein convertase subtilisin/kexin type 9 (PCSK9), alirocumab, and evolocumab, have been approved to lower LDL cholesterol level. While there are drawbacks to the use of PCSK9 inhibitors, including high cost and adverse events such as injection site reaction, they significantly decreased serum LDL cholesterol levels and thereby ASCVD risks when added to maximally tolerated statin therapy.

Beyond conventional secondary prevention in coronary artery disease-what to choose in the era of CANTOS, COMPASS, FOURIER, ODYSSEY and PEGASUS-TIMI 54? A review on contemporary literature.

Patients with established cardiovascular (CV) disease remain at dramatic residual risk for subsequent events, despite growing evidence in secondary prevention and wider dissemination of intensive treatment. This review focuses on new options in secondary risk prevention as presented by these five major randomized controlled trials (RCT): PEGASUS-TIMI 54, COMPASS, FOURIER, ODYSSEY and CANTOS. Three main therapeutic targets are addressed: residual cholesterol, residual inflammatory and residual thrombotic risk. All of the trials reviewed included patients with stable CV disease on optimal medical treatment with a surprising similar mortality. As of now, evolocumab, alirocumab and ticagrelor are on the market, while rivaroxaban and canakinumab are not yet licensed for the treatment of secondary prevention in CV disease. Although life-style modifications and better utilization of established medical treatment options will remain first-line strategy, new medication is just about to enter the market. Secondary prevention in coronary artery disease (CAD) holds a strong potential to reduce subsequent CV events, even CV death. It seems that a combination of an aggressive lipid-lowering treatment in combination with antithrombotic therapy could improve prognosis significantly (at least for distinct subgroups). Against this background, individual efficacy, risk, and costs have to be considered when identifying patients for each new regime.

Inflammatory and Cholesterol Risk in the FOURIER Trial.

In the FOURIER trial (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Patients With Elevated Risk), the PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor evolocumab reduced low-density lipoprotein cholesterol (LDL-C) and cardiovascular risk. It is not known whether the efficacy of evolocumab is modified by baseline inflammatory risk. We explored the efficacy of evolocumab stratified by baseline high-sensitivity C-reactive protein (hsCRP). We also assessed the importance of inflammatory and residual cholesterol risk across the range of on-treatment LDL-C concentrations. Patients (n=27 564) with stable atherosclerotic cardiovascular disease and LDL-C ≥70 mg/dL on a statin were randomly assigned to evolocumab versus placebo and followed for a median of 2.2 years (1.8-2.5). The effects of evolocumab on the primary end point of cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina or coronary revascularization, and the key secondary end point of cardiovascular death, myocardial infarction, or stroke were compared across strata of baseline hsCRP (<1, 1-3, and >3 mg/dL). Outcomes were also assessed across values for baseline hsCRP and 1-month LDL-C in the entire trial population. Multivariable models adjusted for variables associated with hsCRP and 1-month LDL-C were evaluated. A total of 7981 (29%) patients had a baseline hsCRP<1 mg/L, 11 177 (41%) had a hsCRP 1 to 3 mg/L, and 8337 (30%) had a hsCRP >3 mg/L. Median (interquartile range) baseline hsCRP was 1.8 (0.9-3.6) mg/L and levels were not altered by evolocumab (change at 48 weeks of -0.2 mg/dL [-1.0 to 0.4] in both treatment arms). In the placebo arm, patients in higher baseline hsCRP categories experienced significantly higher 3-year Kaplan-Meier rates of the primary and key secondary end points: 12.0%, 13.7%, and 18.1% for the primary end point (Ptrend<0.0001) and 7.4%, 9.1%, and 13.2% for the key secondary end point (Ptrend<0.0001) for categories of <1, 1 to 3, and >3 mg/dL, respectively. The relative risk reductions for the primary end point and key secondary end point with evolocumab were consistent across hsCRP strata (P-interactions>0.15 for both). In contrast, the absolute risk reductions with evolocumab tended to be greater in patients with higher hsCRP: 1.6%, 1.8%, and 2.6% and 0.8%, 2.0%, and 3.0%, respectively, for the primary and key secondary end points across hsCRP strata. In adjusted analyses of the association between LDL-C and hsCRP levels and cardiovascular risk, both LDL-C and hsCRP were independently associated with the primary outcome (P<0.0001 for each). LDL-C reduction with evolocumab reduces cardiovascular events across hsCRP strata with greater absolute risk reductions in patients with higher-baseline hsCRP. Event rates were lowest in patients with the lowest hsCRP and LDL-C. URL: https://www.clinicaltrials.gov. Unique identifier: NCT01764633.

DETERMINATION OF PHYSICAL AND CHEMICAL PROPERTIES OF BLOOD PLASMA AND ASCETIC FLUID IN PATIENTS WITH LIVER CIRRHOSIS

With the aim of individual treatment strategy selection authors studied proteins content as well as both blood plasma and ascites chemical properties characteristics in patients with liver cirrhosis at different stages of its intensity. 262 patients with liver cirrhosis were divided into 4 groups according to diagnostic examination results which revealed different severity of the pathological process in the liver parenchyma. Proteins level, total bilirubin content, the average mass molecules, the residual nitrogen, urea, creatinine, ALT, AST, alkaline phosphatase, cholesterol and lecithin concentrations were determined in blood plasma and ascites of patients with liver cirrhosis. The data obtained reveal protein homeostasis disturbance, atherogenic lipoproteins levels increase that induce hepatocytes membrane structure failure in patients with liver cirrhosis at all stages. Ascites detected components correlated with the liver parenchyma degree of functional activity disturbances. The authors conclude that homeostasis disorders established in patients with liver cirrhosis complicated by ascites should be taken into account in cases of surgical tactics performing out.

Ocena prehranskega stanja starejših v socialnovarstvenem zavodu

Uvod: Eden od dejavnikov kakovosti življenja starejših v socialnovarstvenem zavodu je prehrana. Namen raziskave je bil proučiti prehransko stanje in ponuditi predloge za izboljšanje prehrane starejših v socialnovarstvenem zavodu. Metode: V raziskavi je bila uporabljena kvantitativna opisna metoda raziskovanja. Analizirani so bili dnevni jedilniki v socialnovarstvenem zavodu in na vzorcu starejših (n = 48) izvedena analizo dejanskega vnosa hranil in prehranskega statusa. Prehransko stanje je bilo ugotovljeno na podlagi indeksa telesne mase in vprašalnika Mini prehranski pregled. Vključeni v raziskavo so imeli prehrano, pri kateri dietne prilagoditve niso bile potrebne. Rezultati: Povprečna energijska vrednost ponujenih jedilnikov je znašala 8457 kJ (2021 kcal) na dan, 17 hranil je odstopalo od priporočil. Moški (M) in ženske (Ž) se statistično pomembno razlikujejo v deležu ostanka maščob (μM = 16 %, μŽ = 24 %; p = 0,036), holesterola (μM = 15 %, μŽ = 26 %; p = 0,035), vitamina D (μM = 15 %, μŽ = 27 %; p = 0,017) in vitamina B12 (μM = 17 %, μŽ = 25 %; p = 0,016). Indeks telesne mase je pokazal, da nihče od starejših, ki so bili vključeni v raziskavo, ni bil podhranjen ali v kategoriji debelost III. stopnje. Diskusija in zaključek: Raziskava je potrdila potrebo po sistematičnem spremljanju kakovosti prehrane starejših v socialnovarstvenih zavodih. Da bi starejšim zagotovili ustrezno prehransko oskrbo, je potrebno sodelovanje medpoklicnega tima s starejšimi in njihovimi družinskimi člani.

The study of starter cultures compositions influence on the cholesterol level in fermented meat products

The article considers the possibility of using starter cultures compositions to reduce cholesterol in meat fermented products. An analysis of own researches and other scientific data allowed to conclude that the ability to reduce cholesterol by starting cultures in vitro is the strain-specific property. In view of the technological properties and the ability to reduce cholesterol in vitro, six compositions of starter cultures from the MGUPP collection were suggested. The compositions consisted of microorganisms belonging to the three genuses: Lactobacillus, Pediococcus and Staphylococcus. The absence of antagonism between the strains within each composition was determined by perpendicular strokes. Strains of each composition were co-cultured in a medium containing cholesterol. The residual cholesterol amount in the medium was determined after 24 hours by the Zlatkis- Zakmethod. This method is based on the cholesterol reaction with FeCl3 in the presence of concentrated sulfuric acid and glacial acetic acid to form a yellow colored complex. It was found that the compositions showed stronger activity for cholesterol reduction than each strain separately. Synergistic effect of cholesterol reduction was detected in starter cultures strains included into compositions. Reduction of cholesterol observed at 25.0-45.7%of its initial concentration in the medium. In those compositions, which included strains with a high capacity to reduce cholesterol, total cholesterol degradation ability was also higher. It was found that starter cultures reduced cholesterol not only in vitro, but also in the process of meat raw material fermentation in production of dry-smoked sausage. Composition a (Lactobacillus sakei 105, Pediococcus pentosaceus 31, Staphylococcus xylosus 45 at a ratio of 1:1:1) was chosen for the manufacture of drysmoked sausage. Bacterial composition was introduced into the meat raw materials on the mince preparation step in an amount of 109 CFU/g mince. Cholesterol maintenance in minced meat and ready-made dry-smoked sausages was determined by HPLC. In minced meat it was 840±10 mg/kg. In the ready sausages the greatest amount of cholesterol was detected in the control sample and was 971±15 mg/kg. Increasing cholesterol levels apparently due to loss of product weight by drying. Cholesterol level decreased by 21.4% in the test sample with the addition of bacterial composition (763±12 mg/kg).

How Common Is Residual Inflammatory Risk?

After initiating aggressive statin therapy, high-risk atherosclerosis patients can be classified as having residual cholesterol risk (on-treatment low-density lipoprotein cholesterol [LDLC] ≥70 mg/dL), residual inflammatory risk (on-treatment high-sensitivity C-reactive protein [hsCRP] ≥2 mg/L), both conditions, or neither. In contemporary lipid-lowering trials, there are roughly twice as many individuals in whom the principle unmet clinical need is residual inflammatory risk as compared with residual cholesterol risk. As such, continued translational investigation into inflammatory mediators of plaque initiation, progression, and rupture is crucial for the vascular biology community and ultimately for patient care. A critical principle of personalized medicine is to provide the right therapy to the right patient at the right time. Yet, in the treatment of chronic atherosclerosis, statin therapy has proven so effective that all patients should be aggressively treated for life, typically with high-intensity regimens.1 Addressing the problem of residual risk after statin therapy has proven complex as differing biological processes drive recurrent events in different patients. On the one hand, individuals treated with statins who, nonetheless, have persistently elevated levels of atherogenic lipoproteins represent a group with residual cholesterol risk where additional lipid-lowering therapies, including PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibition, are likely to prove effective. On the other hand, the majority of patients treated with a higher intensity statins will achieve 50% to 85% reductions in LDLC and apolipoprotein B.2,3 For these individuals in whom cholesterol is no longer the primary problem, the translational research community has …

Sex Differences in Inflammatory Markers and Health Status Among Young Adults With Acute Myocardial Infarction: Results From the VIRGO (Variation in Recovery: Role of Gender on Outcomes of Young Acute Myocardial Infarction Patients) Study.

Young women (≤55 years of age) with acute myocardial infarction (AMI) have higher mortality risk than similarly aged men. Elevated inflammatory markers are associated with an increased risk of cardiovascular outcomes after AMI, but little is known about whether young women have higher inflammatory levels after AMI compared with young men. We assessed sex differences in post-AMI inflammatory markers and whether such differences account for sex differences in 12-month health status, using data from 2219 adults with AMI, 18 to 55 years of age, in the United States. Inflammatory markers including high-sensitivity C-reactive protein (hsCRP) and lipoprotein-associated phospholipase A2 were measured 1 month after AMI. Overall, women had higher levels of hsCRP and lipoprotein-associated phospholipase A2 after AMI compared with men, and this remained statistically significant after multivariable adjustment. Regression analyses showed that elevated 1-month hsCRP was associated with poor health status (symptom, function, and quality of life) at 12 months. However, the association between hsCRP and health status became nonsignificant after adjustment for sociodemographics, comorbidities, and treatment factors. Half of these patients had residual inflammatory risk (hsCRP >3 mg/L) compared with a third who had residual cholesterol risk (Low-density lipoprotein cholesterol >100 mg/dL). Young women with AMI had higher inflammatory levels compared with young men. Elevated 1-month hsCRP was associated with poor health status at 12 months after AMI, but this was attenuated after adjustment for patient characteristics. Targeted anti-inflammatory treatments are worthy of consideration for secondary prevention in these patients if ongoing trials of anti-inflammatory therapy prove effective.

Symbiotic, Hypocholesterolemic and Antioxidant Effects of Potential Probiotic Lactobacilli Strains Isolated from Tunisian Camel Milk

In the present study, 20 selected Lactobacillus strains already characterized in a previous research for their capability to grow in conditions simulating the intestinal environment, their resistance to antibiotics, their antibacterial activity and their adhesion capability to intestinal human Caco-2 TC7 and HT-29 MTX cell lines, were further investigated to explore more their probiotic properties. Growth behaviour in the presence of prebiotic (fructooligosac-charides (FOS) and lactulose) at a concentration of 2%, cholesterol removal by measuring the residual cholesterol in medium supplemented with cholesterol, ability to deconjugate bile salts using BSH enzyme and antioxidant activity of culture supernatant of Lactobacillus strains by ABTS·+ and DPPH methods were analyzed. All probiotic strains demonstrated important prebiotic assimilation (P > 0.05) even with OD600 > 3 after 30 h of contact, cholesterol removal ability with maximum percentage of 57% after 24 h of contact and they were found to liberate significantly (P ·+ and DPPH respectively. This study confirmed the suitability of these probiotic strains for application in functional food formulations especially where cholesterol reduction and antioxidant activity in food are needed to assess possible in vivo human health benefits.

Evaluating bococizumab, a monoclonal antibody to PCSK9, on lipid levels and clinical events in broad patient groups with and without prior cardiovascular events: Rationale and design of the Studies of PCSK9 Inhibition and the Reduction of vascular Events (SPIRE) Lipid Lowering and SPIRE Cardiovascular Outcomes Trials

Although statins significantly reduce vascular event rates, residual cholesterol risk remains high in many patient groups, including those with known vascular disease as well as in the setting of high-risk primary prevention. Bococizumab is a humanized monoclonal antibody that inhibits proprotein convertase subtilisin-kexin type 9 (PCSK9), prolongs the half-life of hepatic low-density lipoprotein (LDL) receptors, and reduces circulating atherogenic cholesterol levels. The SPIRE program comprises 6 lipid-lowering studies and 2 cardiovascular outcomes trials, each comparing bococizumab (150 mg subcutaneously every 2 weeks) to matching placebo. The 6 SPIRE lipid-lowering studies include 3 parallel 12-month assessments of bococizumab on atherogenic lipids among statin-treated individuals at high residual risk (SPIRE-HR, SPIRE-LDL, SPIRE-LL), one 12-month study of bococizumab among individuals with familial hypercholesterolemia (SPIRE-FH), one 6-month study of bococizumab among those with statin intolerance (SPIRE-SI), and one 3-month study of bococizumab delivery using an auto-injector device (SPIRE-AI). The SPIRE-1 and SPIRE-2 event-driven cardiovascular outcome trials will assess the efficacy and safety of bococizumab in the prevention of incident vascular events in high-risk populations with and without clinically evident cardiovascular disease who have directly measured entry LDL cholesterol levels ≥70 mg/dL (SPIRE-1, n = 17,000) or ≥100 mg/dL (SPIRE-2, n = 11,000). The SPIRE trials, inclusive of more than 30,000 participants worldwide, will ascertain the magnitude of reduction in atherogenic lipids that accrue with bococizumab and determine whether the addition of this PCSK9 inhibitor to standard treatment significantly reduces cardiovascular morbidity and mortality in high-risk patients, including those without a history of clinical cardiovascular events.

Residual inflammatory risk: addressing the obverse side of the atherosclerosis prevention coin

Twenty-two years ago, the landmark 4S trial demonstrated that statin therapy could reduce rates of recurrent myocardial infarction, stroke, and cardiovascular death among secondary prevention patients with overt hyperlipidaemia.1 Since that time, large-scale statin trials have shown that an exceptionally wide range of patients benefit from statins, including those without evidence of underlying vascular disease or hyperlipidaemia. Yet many statin-treated patients continue to suffer from life-threatening vascular events, an issue commonly described in the clinical literature as the problem of ‘residual risk’. One side of the residual risk coin undoubtedly relates to further reduction in low-density lipoprotein cholesterol (LDLC). Ever more aggressive cholesterol reduction is the cornerstone for proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors that dramatically lower LDLC among those on statins, among those with statin intolerance, and among those with forms of familial hyperlipidaemia characterized by residual LDL receptor function.2–4 In contrast, therapies addressing residual cholesterol risk on the basis of high triglycerides or low HDL cholesterol have not to date proved effective for event reduction in randomized clinical trials. Yet focusing solely on ‘residual cholesterol risk’ among statin-treated patients ignores the fact …

Development and Validation of an Enzymatic Method for Total Cholesterol Analysis Using Whole Blood Spot.

High serum cholesterol represents a risk factor for cardiovascular disease. This study aims to quantify total cholesterol in dried blood spot (DBS) by direct enzymatic method. Three hundred seventeen blood samples with serum cholesterol level ranging from 81 to 337 mg/dl were collected. DBS were manually prepared, cholesterol was extracted using methanol and analyzed by a manual enzymatic method. DBS cholesterol method was validated for imprecision and extraction efficacy. DBS cholesterol values were correlated (training test) with serum values measured by automated enzymatic method (reference method). The obtained correlation was used for predicting serum cholesterol from DBS analysis of a new sample group (validation test, n = 58). Within-day and between-day coefficient of variation (CV%) were lower than 7.69 and 6.32, respectively. Residual cholesterol in DBS after extraction was 16%. DBS cholesterol and serum cholesterol showed a linear correlation (slope = 0.5217; r = 0.9139) and a bias of -28%. Furthermore, DBS cholesterol values of validation test (n = 58), converted using the training test correlation, were not statistically different compared to the corresponding plasma values (P = 0.9487), and the comparison by Passing and Bablok showed a linear regression with a slope of 1.068 (r = 0.611) and a bias of -0.22%. The results show that this enzymatic method is suitable to analyze cholesterol in DBS and it could be automated and used for population screening of total blood cholesterol.

Statin adherence and LDL cholesterol levels. Should we assess adherence prior to statin upgrade?

BackgroundAdherence to statin therapy has been shown to be suboptimal. In statin-treated patients with residual elevated low density lipoprotein cholesterol (LDL-C) levels the physician must decide whether to switch to a more potent statin or try and achieve better adherence. We examined the association between adherence and LDL-C within low, moderate and high intensity statin groups in a “real world” setting. MethodsWe assessed annual adherence by the mean MPR (Medication Possession Ratio = number of purchased/prescribed daily doses) in unselected patient group. Statins were stratified (ACC/AHA Guideline) into low, moderate and high intensity groups. The impact of adherence on LDL levels was assessed by LOESS (locally weighted scatter plot smoothing). ResultsOut of 1183 patients 173 (14.6%) were treated with low, 923 (78.0%) with moderate and 87 (7.4%) with high intensity statins. Statin intensity was inversely associated with adherence (MPR 77±21, 73±22 and 69±21% for low, moderate and high intensity respectively, p=0.018). Non-adjusted LDL levels decreased with higher adherence: a 10% adherence increase resulted in LDL decrease of 3.5, 5.8 and 7.1mg/dL in low, moderate and high intensity groups. Analysis of the adherence effect on LDL levels adjusted for age, DM and ischemic heart disease showed that MPR above 80% was associated with an additional decrease in LDL levels only in the high intensity group. ConclusionsIncreased adherence to statins beyond an MPR of 80% improves LDL levels only among patients given high intensity therapy. Switching from lower to higher intensity therapy may be more effective than further efforts to increase adherence.