Small HDL particles in brain appear protective against Alzheimer’s disease

What does your doctor make of this? S/he is tasked with preventing your likely dementia, or don't they even know of your risks?

Your chances of getting dementia.

1. A documented 33% dementia chance post-stroke from an Australian study?   May 2012.

2. Then this study came out and seems to have a range from 17-66%. December 2013.`    

3. A 20% chance in this research.   July 2013.

4. Dementia Risk Doubled in Patients Following Stroke September 2018 

The latest here:

Small HDL particles in brain appear protective against Alzheimer’s disease

Key takeaways:

• A gene present in 25% of the population, which reduces neuroprotective small HDL production, is associated with increased Alzheimer’s disease risk.
• A drug in early development may be the key to lowering risk.

Small HDL particles play a significant role in the prevention of Alzheimer’s disease, and an inherited gene present in one in four people hinders its production in the brain, increasing risk for cognitive decline, a speaker reported.

New therapeutics in development could improve lipidation and the production of cerebral small HDL particles, but crossing the blood-brain barrier remains a challenge, according to a presentation at the World Congress Insulin Resistance Diabetes & Cardiovascular Disease Conference.

A gene present in 25% of the population, which reduces neuroprotective small HDL production, is associated with increased Alzheimer’s disease risk.
Image: Adobe Stock

“Up to 5 million to 6 million Americans will have Alzheimer’s disease. The fundamental hallmarks of how we make that diagnosis is based on accumulation of amyloid plaques and tau tangles. Advances in PET imaging has allowed us to make biomarkers accessible to living people,” Hussein N. Yassine, MD, the Kenneth and Bette Volk endowed chair of neurology at the University of California, Keck School of Medicine, said during a presentation. “At the moment, the diagnosis of Alzheimer’s disease is getting more and more precise with plasma [Alzheimer’s disease] biomarkers and so forth.”

Yassine said presence of the apolipoprotein E (ApoE) epsilon 4 allele is significantly associated with risk for developing Alzheimer’s disease. With a population prevalence of one in four people, inheritance of the ApoE4 gene from one parent is tied to an up to fourfold increased risk for Alzheimer’s disease, and inheritance from both parents is tied to an up to 10-fold increased risk.

In the brain, apolipoprotein is lipidated to form HDL-like peptides, which are not the same as HDL cholesterol, and starts with a lipid-free ApoA-I or lipid-free ApoE.

After interacting with a transporter known as ATP-binding cassette transporter A1 (ABCA1), a prebeta-1 particle, or very small HDL particle, is created. Remodeling by ABCA1, ATP-binding cassette transporter GI (ABCG1), scavenger receptor type B class I (SR-B1) and lecithin-cholesterol acyltransferase (LCAT) forms small HDL, or HDL3. After further remodeling with LCAT and cholesteryl ester transfer protein (CETP), larger HDL particles — HDL2 — are created, according to the presentation.

“The reason why this is important for Alzheimer’s disease is because if you actually knock out ABCA1 in Alzheimer’s disease models, you accumulate amyloid. ... So it’s not just making lipids. The process of making lipids is also involved in the process of accumulating amyloid in the brain,” Yassine said. “ABCA1 is very important. It doesn’t show up on [genome-wide association studies] because of how important it is, but there has been very close detailed, population studies and the very rare loss-of-function mutations in ABCA1 are associated with an increased risk of Alzheimer’s disease.”

A prior study published in Alzheimer’s & Dementia demonstrated that individuals with cognitive impairment had lower levels of ABCA1 activity of cerebral spinal fluid compared with patients with normal cognitive function.

Citing findings from another study published in the Journal of Neuroscience, Yassine said ApoE aggregation caused by the presence of the ApoE epsilon 4 allele impairs the expression and activity of ABCA1 by trapping the transporter within late endosomes and lysosomes.

“Interestingly, the amount of small HDL particles in [cerebral spinal fluid] were significantly correlated with [cerebrospinal fluid beta-amyloid 42],” Yassine said. “The higher the [cerebrospinal fluid beta-amyloid 42], the less plaques there are. ... So this means more small HDL particles is associated with less amyloid plaques in the brain. This correlation was weaker with large HDL.

“Moreover, when you look at cognitive measures, whether it’s memory, executive function or global cognition, there is a weak but significant correlation between small HDL particles, their concentration in [cerebrospinal fluid] and measures of cognition,” he said.

Based on those findings, Yassine and colleagues developed the ABCA1 agonist CS-6253 — a peptide drug that generates small HDL — from ApoE to protect from ABCA1 degradation and potentially lower risk for Alzheimer’s disease in people with the APOE epsilon 4 allele.

Their initial findings, published in Alzheimer’s Research and Therapy, demonstrated increased plasma prebeta-1 HDL and improved plasma beta-amyloid 42/40 ratio, as a surrogate to brain beta-amyloid 42 clearance, in monkeys. This resulted in increased plasma ApoE.

The researchers reported that, unfortunately, CS-6253 was unable to penetrate the blood-brain barrier.

However, Yassine said research led by Juno S. Van Valkenburgh, PhD, a postdoctoral scholar and research associate at the University of Southern California, Keck School of Medicine, produced a potential solution by coupling a reversed CS-6253 with an angiopep brain delivery peptide.

“Small HDL particles have neuroprotective roles against Alzheimer’s disease pathology. Brain ABCA1 activity is important and drives the formation of small HDL, which is lower in patients with Alzheimer’s disease. ApoE epsilon 4 aggregates and impairs ABCA1 ApoE lipidation recycling of HDL particles,” Yassine said. “Developing therapeutic strategies based on this concept is challenging, but we’re doing the best we can and hopefully we can get something that can get into brain.”

References:

• Martinez AE, et al. Alzheimers Dement. 2022;doi:10.1002/alz.12649.
• Noveir SD, et al. Alzheimers Res Ther. 2022;doi:10.1186/s13195-022-01028-1.
• Rawat V, et al. J Neurosci. 2019;doi:10.1523/JNEUROSCI.1400-19.2019.

Blood Profile at Age 35 Linked to Subsequent Alzheimer's Dementia

 I have zero clue what my readings were 30 years ago. It makes zero difference, your doctor is responsible to have EXACT Alzheimer's prevention protocols right now at your current age.

Blood Profile at Age 35 Linked to Subsequent Alzheimer's Dementia

Associations extend much earlier in life than previously thought

by Judy George, Senior Staff Writer, MedPage Today March 24, 2022

High-density lipoprotein (HDL) cholesterol and triglyceride levels in people as young as age 35 were linked with Alzheimer's dementia decades later in life, longitudinal data from the Framingham Heart Study showed.

Risk of Alzheimer's dementia fell by 15.4% during early adulthood (ages 35 to 50) and by 17.8% during middle adulthood (ages 51 to 60) for every 15 mg/dL increase in HDL cholesterol, reported Xiaoling Zhang, MD, PhD, of Boston University School of Medicine, and co-authors in Alzheimer's & Dementia.

A 15 mg/dL increase in blood glucose measured during middle adulthood was associated with a 14.5% increased Alzheimer's risk, they added. Triglyceride levels were associated with Alzheimer's only in the early adulthood group. Findings remained significant after adjusting for treatment.

"These findings show for the first time that cardiovascular risk factors, including HDL, which has not been consistently reported as a strong risk factor for Alzheimer's disease, contribute to future risk of Alzheimer's disease starting as early as age 35," Zhang said in a statement.

"While our findings confirm other studies that linked cholesterol and glucose levels measured in blood with future risk of Alzheimer's disease, we have shown for the first time that these associations extend much earlier in life than previously thought," added co-author Lindsay Farrer, PhD, also of Boston University.

The researchers looked at the influence of vascular risk factors on incident Alzheimer's dementia over time among Framingham Heart Study Offspring participants, a group that's been evaluated since 1971. Data on lipid fractions, glucose, blood pressure, BMI, and smoking were obtained prospectively from participants across nine quadrennial examinations.

Age-, sex-, and education-adjusted models were tested for each risk factor measured at each exam and within three adult age groups: early adults (ages 35 to 50, median 41), middle adults (ages 51 to 60, median 54), and late adults (ages 61 to 70, median 63.5).

A total of 271 participants (167 women, 104 men) diagnosed with Alzheimer's dementia were included in the analysis as cases. Of these, 225 people were without stroke, 24 people had Alzheimer's and stroke, and 24 people had mixed Alzheimer's and vascular dementia. People with a diagnosis of non-Alzheimer's dementia were excluded. Controls included 4,867 cognitively normal participants.

Mean follow-up periods for people in the early, middle, and late age groups were 35.2 years, 25.8 years, and 18.5 years, respectively. As participants grew older, they tended to have higher triglyceride and glucose levels, higher systolic and diastolic blood pressure, and lower HDL cholesterol levels. They also were more likely to be treated for diabetes, hypertension, and dyslipidemia.

Incident Alzheimer's dementia was negatively associated with HDL cholesterol for every 15 mg/dL increase in early adulthood (HR 0.85, 95% CI 0.72-0.99, P=0.041) and in middle adulthood (HR 0.82, 95% CI 0.70-0.96, P=0.014). This association remained significant with a similar effect size in the middle adulthood group when adjusted for dyslipidemia treatment (P=0.022).

Analyses also showed:

• Triglyceride levels were associated with Alzheimer's dementia only in the early adulthood group, before (HR 1.33, 95% CI 1.02-1.57, P=0.0013) and after (HR 1.30, 95% CI 1.10-1.54, P=0.0018) adjusting for dyslipidemia treatment
• Blood glucose in middle adulthood was associated with Alzheimer's dementia per 15 mg/dL increase, before (HR 1.15, 95% CI 1.06-1.23, P=0.00029) and after (HR 1.18, 95% CI 1.08-1.29, P=0.00036) adjusting for diabetes treatment
• Diastolic blood pressure in late adulthood was associated with Alzheimer's dementia per 10 mm increase, before (HR 1.14, 95% CI 1.01-1.29, P=0.041) and after (HR 1.14, 95% CI 1.00-1.29, P=0.044) adjusting for treatment
• Other vascular risk factors, including low-density lipoprotein (LDL) cholesterol, total cholesterol, BMI, smoking, and systolic blood pressure, were not associated with Alzheimer's dementia in any stage of adulthood (P>0.05)

Future development of Alzheimer's dementia was progressively higher and likely to occur earlier among people who had blood glucose in pre-diabetic (100 to 126 mg/dL) and diabetic (>126 mg/dL) ranges in early adulthood and middle adulthood.

"Intervention targeting cholesterol and glucose management starting in early adulthood can help maximize cognitive health in later life," Farrer suggested.

That idea is supported by previous studies of Framingham Offspring participants showing that elevated coronary heart disease risk and metabolic syndrome were associated with lower cognitive performance at age 55, Zhang and co-authors noted.

"However, our results do not distinguish whether the influences of these risk factors on the development of Alzheimer's disease may be particularly damaging during early adulthood and midlife or reflect longer accumulated risk exposure," they wrote.

The study had several limitations, the researchers acknowledged. All participants were white, and some early measurements of lipids and glucose were not under fasting conditions. In addition, the findings were based on analyses of one-time measurements.

• Judy George covers neurology and neuroscience news for MedPage Today, writing about brain aging, Alzheimer’s, dementia, MS, rare diseases, epilepsy, autism, headache, stroke, Parkinson’s, ALS, concussion, CTE, sleep, pain, and more. Follow

Disclosures

This work was supported by the Framingham Heart Study's National Heart, Lung, and Blood Institute contract, Boston University School of Medicine, the NIH, and the Alzheimer's Association.

Zhang had no disclosures.

Co-authors reported relationships with the Alzheimer's Drug Discovery Foundation, American Heart Association, Gates Ventures, Mass Mutual Insurance, Signant Health, Biogen, GlaxoSmithKline, Novo Nordisk, High Lantern, and the NIH.

Primary Source

Alzheimer's & Dementia

Source Reference: Zhang X, et al "Midlife lipid and glucose levels are associated with Alzheimer's disease" Alzheimer's Dement 2022; DOI: 10.1002/alz.12641.

 

 

HDL Protein Linked to Lower Dementia Risk

This really helps not one bit. How do I as a layperson find out these APOE levels in high-density lipoprotein (HDL)? Then how do I make them better?

HDL Protein Linked to Lower Dementia Risk

Findings extend associations from cardiovascular disease to dementia

by Judy George, Senior Staff Writer, MedPage Today July 14, 2020

Higher apolipoprotein E (APOE) levels in high-density lipoprotein (HDL) were linked to lower dementia risk, but only when HDL did not contain apolipoprotein C3 (APOC3), researchers reported.
Higher APOE levels in whole plasma and in HDL were linked to better cognitive function on the ADAS-Cog (whole plasma β coefficient −0.15; 95% CI −0.24 to −0.06; HDL β coefficient −0.20; 95% CI −0.30 to −0.10) but not to dementia or Alzheimer's disease risk, said Manja Koch, PhD, of Harvard T.H. Chan School of Public Health in Boston, and co-authors, they reported in JAMA Network Open.
The presence of APOC3 appeared to modulate the association between APOE levels in HDL and dementia. Higher APOE levels in HDL that lacked APOC3 were tied to better cognitive function and lower dementia risk:

• ADAS-Cog: per SD β coefficient −0.17; 95% CI −0.27 to −0.07
• Modified Mini-Mental State Examination score: per SD β coefficient 0.25; 95% CI 0.07 to 0.42
• Dementia risk: HR per SD 0.86; 95% CI 0.76-0.99

APOE levels in HDL that contained APOC3 were unassociated with any of these outcomes.
Koch said these findings extend the beneficial associations of the novel APOE–positive, APOC3–negative lipoprotein from cardiovascular disease to dementia.
"Lower apolipoprotein E in plasma is a risk factor for dementia, but the underlying biological mechanisms are not fully understood," Koch told MedPage Today.
The ε4 allele of the APOE gene is the most important known single genetic risk factor for late-onset Alzheimer's disease, though how it increases Alzheimer's risk is unclear. In the general population, low plasma concentrations of APOE protein are associated with higher risk of dementia and Alzheimer's disease, independent of ε2/ε3/ε4 APOE genotype.
Higher APOE levels in plasma HDL previously were found to be associated with lower coronary heart disease risk, but the coexistence of APOC3 modified this lower risk.
In their analysis, Koch and collaborators looked at data from a subset of the Ginkgo Evaluation of Memory Study (GEMS) that included 1,351 community-dwelling participants with a median age of 78; 47% were women. GEMS aimed to study the effect of Ginkgo biloba on dementia and Alzheimer's disease and was conducted from 2000 to 2008.
A total of 995 participants were dementia-free at baseline, and 521 people were diagnosed with incident dementia during a median follow-up of 5.9 years.
The findings "raise the possibility that composition of the HDL-associated proteome may be a key determinant of APOE-associated risk of Alzheimer's disease and all-cause dementia," wrote Madhav Thambisetty, MD, PhD, of the National Institute on Aging in Baltimore, in an accompanying editorial.
They also may have important clinical translational implications, he said.
"As multiple clinical trials have demonstrated the limitations of increasing plasma HDL levels as a therapeutic strategy against coronary artery disease, the potential clinical utility of targeting HDL-associated lipoproteins such as APOC3 has received increasing attention," he noted.
"These approaches may also be relevant to developing novel disease-modifying treatments for Alzheimer's disease including APOE-based therapeutics targeting the complex interactions of these pleiotropic lipid mediators," he added.
This analysis was limited to older participants and findings may not apply to younger populations, Koch and colleagues acknowledged. Cognitive testing was systematic but stopped in GEMS when dementia occurred, they noted. In addition, mild cognitive impairment was not a trial outcome.

Last Updated July 14, 2020

• Judy George covers neurology and neuroscience news for MedPage Today, writing about brain aging, Alzheimer’s, dementia, MS, rare diseases, epilepsy, autism, headache, stroke, Parkinson’s, ALS, concussion, CTE, sleep, pain, and more. Follow

Disclosures

Research was supported by the National Center for Complementary and Alternative Medicine, the National Institute on Neurological Disorders and Stroke, the National Institute on Aging, the National Heart, Lung, and Blood Institute, the University of Pittsburgh Alzheimer's Disease Research Center, the Roena Kulynych Center for Memory and Cognition Research, and Wake Forest University School of Medicine.
Researchers reported relationships with the NIA and NINDS. The editorialist had no disclosures.

Primary Source

JAMA Network Open

Source Reference: Koch M, et al "Association of Apolipoprotein E in Lipoprotein Subspecies With Risk of Dementia" JAMA Network Open 2020; DOI:10.1001/jamanetworkopen.2020.9250.

Secondary Source

JAMA Network Open

Source Reference: Thambisetty M "Plasma Apolipoprotein E Levels and Risk of Dementia -- You Are the Company You Keep" JAMA Network Open 2020; DOI:10.1001/jamanetworkopen.2020.9501.

Daily Consumption of Virgin Coconut Oil Increases High-Density Lipoprotein Cholesterol Levels in Healthy Volunteers: A Randomized Crossover Trial

Not to be followed until your doctor gets around to writing up a diet protocol. Probably decades after you are dead.  

Daily Consumption of Virgin Coconut Oil Increases High-Density Lipoprotein Cholesterol Levels in Healthy Volunteers: A Randomized Crossover Trial

 Surarong Chinwong,1 Dujrudee Chinwong,1 and Ampica Mangklabruks2
1Department of Pharmaceutical Care, Faculty of Pharmacy, Chiang Mai University, Chiang Mai 50200,Thailand
2Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200,Thailand
Correspondence should be addressed to Dujrudee Chinwong; dujrudee.c@cmu.ac.th
Received 20 July 2017; Revised 31 October 2017; Accepted 16 November 2017; Published 14 December 2017
Academic Editor: Norman Temple
Copyright © 2017 Surarong Chinwong et al. This is an open access article distributed under the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly
cited.
This open-label, randomized, controlled, crossover trial assessed the effect of daily virgin coconut oil (VCO) consumption on plasma lipoproteins levels and adverse events.The study population was 35 healthy Thai volunteers, aged 18–25. At entry, participants were randomly allocated to receive either (i) 15mL VCO or (ii) 15mL 2% carboxymethylcellulose (CMC) solution (as control), twice
daily, for 8 weeks. After 8 weeks, participants had an 8-week washout period and then crossed over to take the alternative regimen for 8 weeks. Plasma lipoproteins levels were measured in participants at baseline, week-8, week-16, and week-24 follow-up visits.
Results. Of 32 volunteers with complete follow-up (16 males and 16 females), daily VCO intake significantly increased high-density lipoprotein cholesterol by 5.72mg/dL (𝑝 = 0.001) compared to the control regimen. However, there was no difference in the change in total cholesterol, low-density lipoprotein cholesterol, and triglyceride levels between the two regimens. Mild diarrhea
was reported by some volunteers when taking VCO, but no serious adverse events were reported. Conclusion. Daily consumption of 30mL VCO in young healthy adults significantly increased high-density lipoprotein cholesterol. No major safety issues of taking VCO daily for 8 weeks were reported.

REVEAL: CETP inhibitor added to statin lowers incidence of major coronary events

Would this help reduce the incidence of stroke also?  Since this didn't seem to be one of the endpoints your doctor will never take a chance on giving it to you for that reason. SOMEONE ELSE WILL SOLVE THE PROBLEM?
https://www.healio.com/cardiology/chd-prevention/news/online/%7B5147c337-deb4-425e-8b4e-b0a79ff0adcf%7D/reveal-cetp-inhibitor-added-to-statin-lowers-incidence-of-major-coronary-events?utm_source=selligent&utm_medium=email&
Incidence of major coronary events was significantly reduced among patients with atherosclerotic vascular disease who received statin therapy with the addition of the cholesterol ester transfer protein inhibitor anacetrapib, according to data presented at the European Society of Cardiology Congress.
The findings, which compared statin therapy plus anacetrapib (Merck) to statin therapy plus placebo, were simultaneously published in The New England Journal of Medicine.

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Merck stated in a press release that it is “reviewing the results of the trial with external experts and will consider whether to file new drug applications with the [FDA] and other regulatory agencies.”
“Pharmacological inhibition of cholesterol ester transfer protein (CETP) can produce substantial increases in HDL cholesterol levels, along with reductions in levels of non-HDL cholesterol,” Louise Bowman, MD, FRCP, associate professor at the Clinical Trial Service Unit of the University of Oxford and colleagues wrote in the study. “However, previous randomized clinical outcomes trials of CETP inhibitor therapy were stopped after approximately 2 years of follow-up because of either hazards associated with the therapy or an apparent lack of efficacy.”
Researchers conducted the double-blind, placebo-controlled, phase 3 REVEAL trial to assess the clinical efficacy and safety of anacetrapib in patients with preexisting atherosclerotic vascular disease who were receiving effective therapy with atorvastatin and had a mean LDL cholesterol level of 61 mg/dL, a mean non-HDL cholesterol level of 92 mg/dL and a mean HDL cholesterol level of 40 mg/dL.
A total of 30,449 patients were assigned to receive 100 mg of anacetrapib once daily or matching placebo.
The prespecified primary outcome of the study was the first major coronary event, a composite of coronary death, MI or coronary revascularization. Median follow-up was 4.1 years.
The occurrence of the primary outcome was significantly less frequent among patients in the anacetrapib group compared with the placebo group (10.8% vs. 11.8%; RR = 0.91; 95% CI, 0.85-0.97), Bowman and colleagues found.
Relative difference in risk was consistent across multiple prespecified groups, according to the researchers.
The mean HDL level was higher at by 43 mg/dL and the mean level of non-HDL was lower by 17 mg/dL in the anacetrapib group compared with the placebo group.
The groups did not differ in risk for death, cancer, or other adverse events, according to the researchers.
“During a median of 4 years of follow-up, anacetrapib treatment was not associated with any of the previously hypothesized adverse effects of very low levels of cholesterol (eg, reduced cognitive function, increased cancer incidence or nonvascular death),” the researchers wrote. “We found that the addition of CETP inhibitor anacetrapib to intensive statin treatment in patients with atherosclerotic vascular disease resulted in a significantly lower incidence of major coronary events than the addition of placebo during 4 years of treatment.”
References:
Landray M, et al. Hot Line: Late Breaking Clinical Trials 4. Presented at: European Society of Cardiology Congress; August 26-30, 2017; Barcelona, Spain.
Bowman L, et al. N Engl J Med. 2017;doi:10.1056/NEJMoa1706444.
Disclosure: The study was supported in part by Merck. Bowman reports receiving grants from Merck. Please see the full study for a list of the other authors’ relevant financial disclosures.

Researchers link high levels of ‘good’ cholesterol with excessive mortality

Be careful out there.
https://www.mdlinx.com/medical-student/top-medical-news/article/2017/08/28/7390102

University of Copenhagen Faculty of Health and Medical Sciences News

In striking contrast to the general perception, researchers from the University of Copenhagen have shown in a new study that people with extremely high levels of HDL – the ‘good’ cholesterol – in their blood have a more than 65 percent higher mortality rate than people with normal HDL levels. The researchers say the results should lead to a change in the way ‘good’ cholesterol is perceived.

The results of a new study from the University of Copenhagen seriously contradict the assumption that high levels of HDL in the blood are only a good thing. The researchers have shown that people with extremely high levels of good cholesterol have a higher mortality rate than people with normal levels. For men with extremely high levels, the mortality rate was 106 per cent higher than for the normal group. For women with extremely high levels, the mortality rate was 68 per cent higher.

“These results radically change the way we understand ‘good’ cholesterol. Doctors like myself have been used to congratulating patients who had a very high level of HDL in their blood. But we should no longer do so, as this study shows a dramatically higher mortality rate,” says Børge Nordestgaard, Professor at the Department of Clinical Medicine and one of the authors of the study.

The researchers analysed data for 116,000 subjects from the Copenhagen City Heart Study and the Copenhagen General Population Study, in combination with mortality data from the Danish Civil Registration System. They have followed the subjects for an average of 6 years, and based the study on just over 10,500 deaths.

The researchers were able to calculate the mortality rate based on these deaths and medical information on the subjects. The results showed that men with extremely high HDL levels in the blood had a 106 per cent higher mortality rate than men with a normal HDL level. Among women, those with extremely high levels of HDL had a 68 per cent higher mortality rate than the normal group. Men in the next group, with very high levels, also had a 36 per cent higher mortality rate.

0.4 per cent of the men and 0.3 per cent of the women covered by the study had an extremely high level of HDL in their blood, and a further 1.9 per cent of the men had a very high level.

The study also found excessive mortality for people with extremely low levels of HDL in the blood. The people with medium levels of HDL in the blood had the lowest mortality. For men, this level was 1.9 mmol/L. For women, it was 2.4 mmol/L.

Earlier US studies have shown similar correlations between good cholesterol and excessive mortality among specific population groups, but this is the first time excessive mortality has been shown in the general population. Professor Børge Nordestgaard, who also works as a consultant doctor at the Department of Clinical Biochemistry at Herlev and Gentofte Hospital, hopes the results can change our perception of HDL.

“It appears that we need to remove the focus from HDL as an important health indicator in research, at hospitals and at the general practitioner. These are the smallest lipoproteins in the blood, and perhaps we ought to examine some of the larger ones instead. For example, looking at blood levels of triglyceride and LDL, the ‘bad’ cholesterol, are probably better health indicators,” he notes.

The new study examines the statistical correlation between mortality and HDL levels. It therefore cannot explain why people with extremely high or low HDL levels have higher mortality.

The study titled, “Extreme high high–density lipoprotein cholesterol is paradoxically associated with high mortality in men and women: two prospective cohort studies,” was published in the European Heart Journal on 23 August 2017.

Scientists reveal engineered fusion protein that could recover blood vessel health

Now to do some followup research to see exactly how this could help stroke recovery. But that will never occur. 

Scientists reveal engineered fusion protein that could recover blood vessel health

• Download PDF Copy

August 16, 2017

Scientists from Boston Children's Hospital Vascular Biology Program have revealed an engineered fusion protein that could recover blood vessel health following the onset of hypertension, atherosclerosis, stroke, heart attack, and other cardiovascular diseases. The findings were published today in Science Signaling.
On average, each person has 60,000 miles of blood vessels coursing through his or her body. There are a number of mechanisms that the body uses to keep its vast vascular network healthy, including a tiny fat molecule, a lipid called S1P, that plays a particularly important role.
S1P receptors dot the surface of the endothelium, a layer of cells that line the inside of all the body's blood cells. Together, these so-called endothelial cells form a barrier between the body's circulating blood and surrounding tissue. When S1P molecules activate their receptors, it suppresses endothelial inflammation and generally helps regulate cardiovascular health.
Now, researchers led by Timothy Hla, PhD, from the Boston Children's Vascular Biology Program, have designed a novel therapeutic fusion that could trigger increased S1P receptor activity and recover blood vessel health following the onset of a range of cardiovascular diseases.
Seeking stability
As crucial as S1P is to our health, it can't do its job alone. Instead, S1P relies on another set of the body's molecules to ferry it through the bloodstream so that it can find and bind with its cell receptors on the endothelium.
"High density cholesterol (HDL) -- also known as good cholesterol -- carries a protein called ApoM, which in turn attracts and binds S1P in its cargo," says Hla, an investigator in the Vascular Biology Program, Patricia K. Donahoe Professor Surgery at the Harvard Medical School and the senior author on the new paper. "Together, this trio activates S1P receptors and promotes endothelial cell function and, ultimately, blood vessel repair."
But, mimicking this trio in a therapeutic derivation would not be as straightforward. HDL, a highly-complex and large nanoparticle decorated with a plethora of proteins and lipids in addition to ApoM, is very difficult to synthesize and produce in the lab. So, Hla strategized on how to optimize ApoM, the linker protein between HDL and S1P.

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Hla knew from previous studies in mice that synthetically-derived ApoM is unstable, only having a 15-minute half-life inside the body's blood stream. To make a therapeutic impact and deliver more S1P to their receptors, Hla would need to make ApoM last much longer on its own.
Making a better carrier for S1P
To engineer a much more stable version of ApoM in their laboratory, Hla's team took a cue from the immune system. They adapted a highly-stable antibody fragment called Fc and fused it to synthetic ApoM.
To test its therapeutic efficacy, Hla and his team gave their engineered ApoM-Fc in combination with S1P to groups of mice with different models of vascular disease and injury. Together, the ApoM-Fc fusion had a staggeringly longer half-life than ApoM alone, lasting for up to 90 hours within the blood stream. Inside the mice's blood, ApoM-Fc robustly activated S1P receptors on the blood vessel's endothelial cells. Strikingly, the therapeutic combination of ApoM-Fc and S1P reduced blood pressure in hypertensive mice, mitigated tissue damage from heart attack and boosted brain tissue recovery after stroke.
"If you provide engineered ApoM-Fc with S1P, we see a clear therapeutic benefit in preclinical animal models," says Hla. "In mice, it allowed blood vessels to better repair themselves after various types of disease and injury - so we are eager to see if this is something that could one day translate into the clinic."​​

Source:

http://www.childrenshospital.org/

Rethinking good cholesterol A high HDL cholesterol level may not be as beneficial as once believed.

What does your doctor think?
http://www.health.harvard.edu/heart-health/rethinking-good-cholesterol?utm_source=delivra&utm_medium=email&utm_campaign=WR20170707-Cholesterol&utm_id=557639&dlv-ga-memberid=10994398&mid=10994398&ml=557639
If you're hoping to avoid heart disease, you probably keep tabs on your blood cholesterol values — especially your low-density lipoprotein (LDL), or "bad" cholesterol. Too much LDL in the bloodstream helps to create the plaque that accumulates inside arteries, raising the risk of a heart attack. The lower your LDL, the lower your risk of having a heart attack.
In contrast, high-density lipoprotein (HDL) has long been known as the "good" cholesterol. These particles are known to patrol blood vessels, grabbing cholesterol from both the bloodstream and artery walls and ferrying it to the liver for recycling and disposal. In population-based studies, people with high HDL levels tend to have fewer heart attacks, while those with lower HDL values have more.

HDL: Just a bystander?

But the HDL story is more complex than doctors initially thought. It turns out that not all HDL is created equal (see "The many faces of HDL"). Instead of acting as the good guy that helps lower heart disease risk, HDL may be more of a bystander.
"We're now realizing that HDL appears to be a marker for other factors that raise or lower the risk of a heart attack," says Dr. Christopher Cannon, professor of medicine at Harvard Medical School and a cardiologist at Brigham and Women's Hospital.
People with low HDL levels (see "Lipid lowdown: The numbers to know") tend to have other problems closely linked to higher cardiovascular risk, such as being overweight and having diabetes. "When you see a low HDL value, it's often a middle-aged man with a big belly who has high blood sugar and high blood pressure," says Dr. Cannon. It may be that those factors, rather than the low HDL, are behind the higher risk, he explains.

The many faces of HDL Cholesterol, a waxy, pale yellow lipid, travels through the bloodstream in tiny, protein-covered particles called lipoproteins that mix easily with blood. While low-density lipoproteins (LDL) are rich in cholesterol, high-density lipoproteins (HDL) contain more protein. But that's just the beginning: there are also very-low-density and intermediate-density particles, as well as subcategories within these different lipoprotein classes. HDL, for example, comes in different shapes and sizes. Some types are spherical, while others are doughnut-shaped. Some types of HDL are great at plucking cholesterol from LDL and artery walls, while other types are indifferent to cholesterol, and some even transfer cholesterol the wrong way — into LDL and cells. Researchers are investigating this phenomenon using a test known as cholesterol efflux capacity testing. Currently available only in research settings, the test reveals how effective HDL particles are at moving cholesterol out of plaques and back to the liver. Preliminary findings suggest that high scores are linked to a lower heart disease risk, meaning the test might one day prove useful for predicting heart attack risk.

Genetic research and drug trials

But two major lines of evidence have also put HDL in a less-than-positive light. The first comes from studies of people with genetic mutations that cause high HDL. If high HDL truly protects against heart disease, those people should have fewer heart attacks. But they don't — they're just as likely to have heart disease as people without HDL-raising mutations. The second body of evidence is perhaps even more incriminating: To date, five major clinical trials that sought to raise HDL levels with drugs have failed to lower heart disease risk. These trials included several investigational new drugs as well as an old standby, niacin. Many people continue to take niacin, despite the fact that last year, the FDA withdrew its approval for using niacin-containing drugs as add-on drugs for treating cholesterol problems, Dr. Cannon notes.
What does all this mean for people with low HDL? Think of it as a warning to pay attention to your other numbers, especially your LDL, which should still be your primary focus. Aim for an LDL of 100 or lower, ideally through lifestyle changes such as weight loss, a healthy diet, and exercise, plus cholesterol-lowering statins, if indicated. These measures — especially exercise — may also nudge up your HDL. Vigorous workouts that make you sweat seem to be the most effective.
On the flip side, people with high HDL shouldn't assume that it cancels out a high LDL, as some physicians still believe. Again, your main goal should be to keep your LDL in a healthy range, Dr. Cannon says.

Lipid lowdown: The numbers to know
Test	General desirable level
Total cholesterol	Under 200mg/dL
LDL cholesterol	Under 100 mg/dL
HDL cholesterol	Over 40 mg/dL for a man, over 50 mg/dL for a woman
Tryglycerides	Under 150 mg/dL

Test for HDL cholesterol function could transform the way healthcare providers predict risk for heart disease

Way in the future, but still going down the cholesterol route instead of stopping inflammation.
https://medicalxpress.com/news/2017-06-hdl-cholesterol-function-healthcare-heart.html
A groundbreaking study published today in AACC's Journal of Applied Laboratory Medicine shows that a new test could improve diagnosis and treatment of heart disease by measuring how effectively a patient's high-density lipoprotein cholesterol (HDL-C) cleans up arterial cholesterol.

While scientists have yet to fully elucidate how HDL-C—the good cholesterol—protects against heart disease, one of its chief functions is thought to be mediating the removal of cholesterol from blood vessel walls. Recent studies have indicated that the ability of a patient's HDL-C to do this—known as its cholesterol efflux capacity—is a better gauge of cardiovascular disease development than HDL-C levels on their own. This means, for example, that a patient with low levels of HDL-C but optimal cholesterol efflux capacity could be protected against heart disease to a greater degree than a patient with high levels of HDL-C but low cholesterol efflux capacity. However, the standard research procedures for measuring cholesterol efflux capacity involve radioisotope-labeled cholesterol and cultured macrophages, making these methods too complex and time-consuming for use in patient testing.

In this study, a team of Japanese researchers led by Amane Harada, PhD, of Sysmex Corporation and Ryuji Toh, MD, PhD, of Kobe University Graduate School of Medicine have developed a test for HDL-C function that is simple enough for clinical use. With a turnaround time of less than 6 hours, the test determines cholesterol uptake capacity—the ability of HDL-C to accept additional cholesterol—which the researchers found correlates with cholesterol efflux capacity but is easier to measure. The researchers evaluated the test in 156 patients who had undergone revascularization (such as a stent or bypass) due to coronary artery disease and who had subsequently decreased their low-density lipoprotein—or bad—cholesterol to

If further trials validate this test, in the future, it could enable healthcare providers to use cholesterol uptake capacity in conjunction with HDL-C levels to better predict who is at risk for cardiovascular disease onset or recurrence. This test could also be used to develop new treatments that increase cholesterol efflux capacity and to monitor their efficacy in patients.

"A more efficient enhancement of the atheroprotective functions of HDL may decrease the risk of atherosclerosis and [cardiovascular disease], although it has been difficult to develop therapeutic drugs with the expected effects," wrote Harada and Toh in this paper. "We consider that this can be explained in part by the lack of a convenient assay system to evaluate HDL functionality without complicated or time-consuming procedures. In this respect, our cholesterol uptake assay provides a concise, accurate, and robust system for high-throughput analysis at low cost."

Explore further: What you need to know about cholesterol

More information: Cholesterol Uptake Capacity: A New Measure of HDL Functionality for Coronary Risk Assessment. Journal of Applied Laboratory Medicine, Jun-2017 DOI: 10.1373/jalm.2016.022913

A groundbreaking study published today in AACC's Journal of Applied Laboratory Medicine shows that a new test could improve diagnosis and treatment of heart disease by measuring how effectively a patient's high-density lipoprotein cholesterol (HDL-C) cleans up arterial cholesterol.

While scientists have yet to fully elucidate how HDL-C—the good cholesterol—protects against heart disease, one of its chief functions is thought to be mediating the removal of cholesterol from blood vessel walls. Recent studies have indicated that the ability of a patient's HDL-C to do this—known as its cholesterol efflux capacity—is a better gauge of cardiovascular disease development than HDL-C levels on their own. This means, for example, that a patient with low levels of HDL-C but optimal cholesterol efflux capacity could be protected against heart disease to a greater degree than a patient with high levels of HDL-C but low cholesterol efflux capacity. However, the standard research procedures for measuring cholesterol efflux capacity involve radioisotope-labeled cholesterol and cultured macrophages, making these methods too complex and time-consuming for use in patient testing.
In this study, a team of Japanese researchers led by Amane Harada, PhD, of Sysmex Corporation and Ryuji Toh, MD, PhD, of Kobe University Graduate School of Medicine have developed a test for HDL-C function that is simple enough for clinical use. With a turnaround time of less than 6 hours, the test determines cholesterol uptake capacity—the ability of HDL-C to accept additional cholesterol—which the researchers found correlates with cholesterol efflux capacity but is easier to measure. The researchers evaluated the test in 156 patients who had undergone revascularization (such as a stent or bypass) due to coronary artery disease and who had subsequently decreased their low-density lipoprotein—or bad—cholesterol to
If further trials validate this test, in the future, it could enable healthcare providers to use cholesterol uptake capacity in conjunction with HDL-C levels to better predict who is at risk for cardiovascular disease onset or recurrence. This test could also be used to develop new treatments that increase cholesterol efflux capacity and to monitor their efficacy in patients.
"A more efficient enhancement of the atheroprotective functions of HDL may decrease the risk of atherosclerosis and [cardiovascular disease], although it has been difficult to develop therapeutic drugs with the expected effects," wrote Harada and Toh in this paper. "We consider that this can be explained in part by the lack of a convenient assay system to evaluate HDL functionality without complicated or time-consuming procedures. In this respect, our cholesterol uptake assay provides a concise, accurate, and robust system for high-throughput analysis at low cost."

Explore further: What you need to know about cholesterol

More information: Cholesterol Uptake Capacity: A New Measure of HDL Functionality for Coronary Risk Assessment. Journal of Applied Laboratory Medicine, Jun-2017 DOI: 10.1373/jalm.2016.022913


Read more at: https://medicalxpress.com/news/2017-06-hdl-cholesterol-function-healthcare-heart.html#jCp

Discovery Could Help Doctors Spot Cardiovascular Disease at Earlier Stage

See what your doctor thinks of this, would it have predicted your event?
http://www.rdmag.com/news/2017/02/discovery-could-help-doctors-spot-cardiovascular-disease-earlier-stage?
Screening methods for cardiovascular diseases such as heart attacks and strokes could be improved by measuring different biological signposts to those currently being tested, a new study led by researchers from King's College London suggests.
Published in the Journal of the American College of Cardiology, the study could allow doctors to better predict the development of cardiovascular disease at an earlier stage.
The research, which was supported by the National Institute for Health Research (NIHR) Biomedical Research Centre at Guy's and St Thomas' NHS Foundation Trust and King's College London, explored the role of a family of proteins called apolipoproteins.
Currently, the main focus is on apolipoprotein A1 (apoA1), the main component of high-density lipoproteins (HDL) or 'good' cholesterol, and apolipoprotein B (apoB), which is present on low-density lipoproteins (LDL) or 'bad' cholesterol.
However, for the first time, researchers have used a technology called mass spectrometry to measure an unprecedented number of apolipoproteins in a population-based study and discovered that another group of apolipoproteins might complement the signposts of good and bad cholesterol: apoE, apoC2 and apoC3.
These apolipoproteins are associated with very low-density lipoproteins (VLDL) and predominantly linked to another type of fat called triglycerides. ApoE, apoC2 and apoC3 have shown a stronger association with cardiovascular disease than apoA1 and apoB, suggesting that currently some of the most predictive apolipoproteins are not measured in patients who may be at risk of cardiovascular disease.
The findings could lead to a change in the way patients all over the world are screened for cardiovascular disease, a condition which affects seven million people and causes more than 160,000 deaths in each year in the UK. It could also pave the way for more personalised treatments.
Lead author of the study Professor Manuel Mayr from King's College London said:
"We directly compared the association of a broad panel of apolipoproteins to new onset of cardiovascular disease over a 10-year observation period, and found that while apoB was predictive, other apolipoproteins, namely apoE, apoC2 and apoC3, were even better.
"These unexpected strong associations of VLDL-associated apolipoproteins with cardiovascular disease provide support to expanding the current measurements of apolipoproteins and to the concept of targeting additional apolipoproteins to reduce risk."
The study identified apoC3 as a prime therapeutic target for lowering VLDL, which might reduce excess cardiovascular risk related to high VLDL.

Mediterranean Diet Boosts HDL Function

Pretty much useless information. They don't point to a SPECIFIC diet protocol. But it is great conscience laundering for them, thinking they are providing help.

Mediterranean Diet Boosts HDL Function

• by Alexandria Bachert
  Staff Writer, MedPage Today February 13, 2017
• This article is a collaboration between MedPage Today® and:
  

Action Points

• Adherence to a traditional Mediterranean diet (TMD) enriched with virgin olive oil improved HDL function in humans, according to a year-long dietary study.
• Note that the data indicated a dissociation between the effects of a TMD on HDL-C levels, which trended lower, versus effects on HDL cholesterol efflux capacity (CEC), which was significantly increased.

A Mediterranean diet rich in virgin olive oil improved high-density lipoprotein (HDL) function in individuals with high-cardiovascular risk, reported researchers.
Compared with both a traditional Mediterranean diet (TMD) enriched with nuts and a low-fat control diet, adherence to a TMD enriched with olive oil decreased cholesteryl ester transfer protein activity (relative to baseline, P=0.028), reported Montserrat Fitó, MD, PhD, coordinator of the Cardiovascular Risk and Nutrition Research Group at the Hospital del Mar Medical Research Institute in Barcelona, and colleagues.
It also increased HDL's ability to esterify cholesterol, paraoxonase-1 arylesterase activity, and HDL vasodilatory capacity (relative to control, P=0.039, P=0.012, and P=0.026, respectively), they wrote in Circulation.
"Following a Mediterranean diet rich in virgin olive oil could protect our cardiovascular health in several ways, including making our 'good cholesterol' work in a more complete way," Fitó stated in a press release.
Writing in an accompanying editorial, Daniel J. Radar, MD, of the University of Pennsylvania in Philadelphia, noted that the findings increase understanding of how dietary intervention can affect HDL functionality.
"Hernáez et al demonstrate a dissociation between the effects of a TMD on HDL-C levels (trending lower) versus on HDL CEC [cholesterol efflux capacity] (significantly higher) and greater positive effects of the TMD on CEC compared with those of a low-fat diet.
"Although efforts to promote HDL CEC through pharmacological means are still in clinical development, these results indicate that a Mediterranean diet is a practical lifestyle-focused approach to improving HDL function and has the proven benefit of reducing cardiovascular risk and the potential to reduce the progression of age-related macular degeneration. Whether promotion of HDL CEC causally contributes to the benefits of the Mediterranean diet remains to be established," he wrote online.
Fitó and colleagues randomly selected a subsample of 296 people at high risk of cardiovascular disease among those participating in the PREDIMED (PREvención con DIeta MEDiterránea) study. The participants (mean age 66) provided blood samples at both the beginning and the end of the 1-year study period. They were randomly assigned to one of three diets:

• A traditional Mediterranean diet enriched with virgin olive oil (about 4 tablespoons) each day (n=100)
• A traditional Mediterranean diet enriched with extra nuts (about a fistful) each day (n=100)
• A healthy "control" diet that reduced consumption of red meat, processed food, high-fat dairy products and sweets (n=96)

Both Mediterranean diets emphasized fruits, vegetables, legumes, and whole grains, as well as moderate amounts of fish and poultry.
Using statistical analyses, Fitó's team assessed the effects of both TMDs on the role of HDL particles on reverse cholesterol transport (cholesterol efflux capacity, HDL ability to esterify cholesterol, and cholesteryl ester transfer protein activity), HDL antioxidant properties (paraoxonase-1 arylesterase activity and total HDL antioxidant capacity on low-density lipoproteins), and HDL vasodilatory capacity (HDL ability to induce the release of nitric oxide in endothelial cells).
The researchers also studied the effects of a TMD on several HDL quality-related characteristics (HDL particle oxidation, resistance against oxidative modification, main lipid and protein composition, and size distribution).
Fitó and colleagues found a decline in total cholesterol levels among those on the low-fat control diet (P=0.039 and P=0.007 relative to baseline and the TMD olive oil, respectively) -- mainly due to a decrease in LDL cholesterol levels (P=0.019 and P=0.004 relative to baseline and the TMD olive oil, respectively).
The TMD with olive oil and with nuts both increased cholesterol efflux capacity relative to baseline (P=0.018 and P=0.013, respectively), but the low-fat diet did not yield significant results.
Additionally, the content of triglycerides in HDL core decreased significantly after both the TMD olive oil and TMD nuts interventions compared with the low-fat diet (P=0.027 and P=0.035, respectively).
All three diets increased the percentage of large HDL particles (relative to baseline, P<0 .001="" p=""> Fitó and colleagues wrote they were surprised that the low-fat diet, which was rich in fruits and vegetables just like the Mediterranean diets, had a negative impact on HDL's anti-inflammatory properties.
They also discussed several possible explanations for the TMD-mediated increase in HDL functionality, including an improvement in the oxidative status of the lipoprotein and a better HDL composition profile.
Radar, too, had several theories for the differences observed between the TMD and the low-fat diet: "One possible difference is alcohol intake. The TMD participants were instructed that 'when the volunteer consumed alcohol, to moderately drink red wine (1 small glass/meal),' whereas the low-fat diet participants were given no similar instructions. Alcohol consumption is known to influence HDL-C levels and has been shown in a small experimental study to promote CEC."
The researchers concluded that "further studies are warranted to investigate the mechanism by which the TMD improves HDL function and whether these properties convey cardioprotective effects."
"Our study could be useful to remind that the Mediterranean Diet is beneficial even through unexpected mechanisms, highlighting again the importance of taking care of our cardiovascular health through a simple and cheap way such as a healthy diet," Fitó explained to MedPage Today.
Studying the cardioprotective mechanisms of an antioxidant-rich diet may contribute to the development of future therapeutic targets oriented to improve HDL functions, he added.
Study limitations were the inclusion of elderly people at high cardiovascular risk which may prevent extrapolation of the results to the general population.
Fitó noted a final limitation: "Some of the techniques used to measure HDL functions, although they were non-invasive and highly-sensitive, were in vitro simulations of processes that happen in our arteries (such as the removal of cholesterol or the ability of HDLs to induce the relaxation of blood vessels). These tests may not fully reflect the real complexity of the previous cardiovascular phenomena," he wrote to MedPage Today.

This work was funded by Agència de Gestió d'Ajuts Universitaris i de Recerca, CIBER de Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, and the Spanish Ministry of Education, Culture and Sport.
The researchers reported no financial disclosures of interest.

• Reviewed by Henry A. Solomon, MD, FACP, FACC Clinical Associate Professor, Weill Cornell Medical College and Dorothy Caputo, MA, BSN, RN, Nurse Planner

• Primary Source

  Circulation

  Source Reference: Rader D "Mediterranean approach to improving high density lipoprotein function" Circulation 2017; DOI: 10.1161/CIRCULATIONAHA.117.026278.

• Secondary Source

  Circulation

  Source Reference: Hernáez A, et al "Mediterranean diet improves high-density lipoprotein function in high-cardiovascular-risk individuals" Circulation 2017; DOI: 10.1161/CIRCULATIONAHA.116.023712.

A beer a day helps prevent stroke and heart disease, new study suggests

Your doctor will never suggest this even if they do read this research. Don't do this on your own, you know how dangerous beer is without a prescription.
Don't know why we should believe this when HDL improving drugs were flopping in clinical trials.

HDL-targeted therapies: progress, failures and future

A beer a day helps prevent stroke and heart disease, new study suggests

 

A pint of beer a day could help reduce the risk of having a stroke or developing cardiovascular disease, new research has found.

A study of 80,000 adults found the natural decline in high-density lipoprotein (HDL), or “good” cholesterol, in the body was slowed by a moderate intake of alcohol.
The results showed that one or two daily servings of alcohol for a man, or up to one for a woman, was associated with a slower HDL decline than either not drinking at all, or drinking too heavily.

 While the trend applied to both beer and spirits, the effect was most visible for drinkers of beer, the Pennsylvania State University study found.

 

The research, which was conducted among Chinese adults, did not yield enough data on the effect of HDL decline from wine consumption to be able to draw conclusions.
Current UK Government advice recommends that both men and women should not drink more than 14 units of alcohol each week, the equivalent of six pints of average strength beer.
The previous guidelines, ditched in January this year, advised a limit of 21 units for men and 14 for women.

Presented at a meeting of the American Heart Association, the new research showed that moderate drinking arrested the decline in HDL as people get older more than twice as much than heavy drinking, which is defined as more than one daily serving of alcohol women and more than two for men.
The scientists said more studies were needed to determine whether the alcohol-HDL association applied to non-Chinese populations.

Study of Israelis and Palestinians calls for rethinking how HDL protects against coronary heart disease

Can no one get out of this fixation on cholesterol?  You fucking idiots, cholesterol is not the problem, inflammation is, which grabs the cholesterol out of the bloodstream packing it into plaque.  Learn about cause and effect and stop trying to force statins to be the only solution.
http://medicalxpress.com/news/2016-08-israelis-palestinians-rethinking-hdl-coronary.html

The idea that plasma high-density lipoprotein cholesterol (HDL-C) is protective against coronary heart disease has been part of medical conventional wisdom for five decades. HDL-C has traditionally been considered the most important component of so-called "good cholesterol" HDL. However, drug trials that increased HDL-C have failed to support a causal role for the amount of cholesterol carried in HDL in reducing the risk of coronary heart disease.

With advances in the separation of lipoproteins by size and functionality, research has intensified to identify HDL measures that may be better predictors of coronary heart disease than the traditional HDL-C. Recent evidence suggests that small, dense, protein-rich particles in HDL may be more atheroprotective than large, buoyant cholesterol-rich particles.
To explore this further, 274 Arabs and 230 Jews residing in Jerusalem were recruited for a new study by researchers at the Braun School of Public Health in the Hebrew University of Jerusalem's Faculty of Medicine. This work, led by Prof. Jeremy Kark of the Hebrew University-Hadassah Braun School of Public Health and Community Medicine, was undertaken by Dr. Chobufo Ditah, a physician from Cameroon, as his thesis for the Braun School's International Masters of Public Health program.
The researchers used Nuclear Magnetic Resonance (NMR) spectroscopy to identify the numbers and sizes of plasma HDL particles, and helical CT-scanning to identify calcification in their coronary arteries, reflecting the overall burden of coronary atherosclerosis. With these data in hand, they looked for associations between the concentrations and sizes of different HDL particles, and coronary artery calcification.
Their findings, published in the prestigious journal Atherosclerosis, showed a statistically significant inverse association of both the number of HDL particles (HDL-P) and the concentration of small and medium-sized HDL particles (MS-HDL-P) with coronary artery calcification, after adjusting for age, statin use, smoking, and other factors. There was no association between large HDL-P and coronary artery calcification in either population group. The association with HDL-C was weaker and inconsistent between men and women.
"Our findings indicate that HDL-P and MS-HDL-P are better independent markers of coronary artery disease, as reflected by coronary artery calcification, than HDL-C, at least in this bi-ethnic population of Israelis and Palestinians," said Dr. Chobufo Ditah.
"These findings support previous reports, based on studies in other population groups, suggesting that small dense HDL particles are protectively associated with risk of coronary heart disease. The consistency of this finding in a new population of urban Arabs and Jews, using different disease outcomes and different separation methods, add more strength to those findings," added Dr Ditah.
"With a better understanding of HDL's complexity and a better ability to measure its components, it is now possible to move past HDL-C to more refined measures that better reflect HDL's role in coronary heart disease risk. Based on the accumulating evidence, incorporation of MS-HDL-P or HDL-P into the routine prediction of coronary heart disease risk should be considered," said Prof Jeremy Kark.

Explore further: Some HDL, or 'good' cholesterol, may not protect against heart disease

More information: Small and medium sized HDL particles are protectively associated with coronary calcification in a cross-sectional population-based sample. Atherosclerosis, Volume 251, August 2016, Pages 124–131. Chobufo Ditah, James Otvos, Hisham Nassar, Dorith Shaham, Ronit Sinnreich, Jeremy D. Kark. DOI: 10.1016/j.atherosclerosis.2016.06.010

Provided by: Hebrew University of Jerusalem

Studies Spotlight Role Of Triglycerides, Put HDL In The Background

See how long it takes before your doctor changes their narrative on causes of cardiovascular disease. I'm guessing 50 years, long enough for all current doctors to die or retire and maybe enough time to get it into medical school curriculum.  But they still won't have attacked the actual problem. INFLAMMATION!
http://cardiobrief.org/2016/03/11/studies-spotlight-role-of-triglycerides-put-hdl-in-the-background/
Two new studies provide more evidence tilting the balance in favor of triglycerides rather than HDL playing a causative role in cardiovascular disease. But it is still too early to know whether the findings of any of the studies will point to useful new methods to prevent and treat disease.

Actual studies are pointed at in the link.

Targeting dangerous inflammation inside artery plaque

I would think that this would be vastly more important for prevention of strokes than statins.  But since we don't have an effective stroke association this will not be followed up to make a translational stroke protocol out of this. Unless you are willing to wait 50 years and your grandchildren have strokes before doing anything about this. Screaming in your doctors face would be a good start.
http://medicalxpress.com/news/2015-04-dangerous-inflammation-artery-plaque.html
A research team showed that a nanotherapeutic medicine can halt the growth of artery plaque cells resulting in the fast reduction of the inflammation that may cause a heart attack, according to a study led by researchers from Icahn School of Medicine at Mount Sinai and published April 3 in Science Advances.

In just one week our novel cell proliferation-specific approach successfully suppressed atherosclerotic plaque growth and inflammation in mice engineered to mimic human vascular disease," says lead study author Jun Tang, MS, a PhD student at Icahn School of Medicine at Mount Sinai. "Atherosclerosis is a major cause of death around the globe, and our nanomedicine strategy promises to offer a new way to reduce the number of heart attacks and strokes."

Building upon a recent discovery by their Massachusetts General Hospital research collaborators that macrophage proliferation dictates atherosclerosis-related vessel wall inflammation, the Mount Sinai research team applied a nanomedicine strategy with a molecule of "good cholesterol," or high-density lipoprotein (HDL), a naturally occurring shuttle that travels from the liver to arteries. The research team took advantage of HDL's natural travel routes, loading it with the widely-used cholesterol-lowering medication called simvastatin (Zocor), which it shuttles into arterial walls.
The simvastatin-loaded nanoparticles, named S-HDL, work by targeting inflamed immune cells called macrophages within high-risk arterial plaques. These macrophages become laden with cholesterol and start proliferating in plaques, thereby increasing inflammation. This lipid-driven inflammatory process drives atherosclerotic plaque buildup and rupture leading to a heart attack or stroke.
Since patients hospitalized after heart attack or stroke have a high recurrence rate of up to 20 percent within three years, the researchers also tested the possible benefits of adding an eight-week regimen of oral statins after the one-week S-HDL nanotherapy. Mice study results showed superior long-term therapeutic benefits of a combined total nine-week S-HDL and oral statins regimen, by first rapidly reducing plaque inflammation and then continuously keeping it suppressed.
"We envision our S-HDL nanomedicine therapy could be translated quickly to human clinical trials as a short-term infusion therapy for heart attack and stroke patients to rapidly suppress plaque inflammation, which can be sustained using current standard of care oral statin medication," says Zahi Fayad, PhD, Professor of Radiology and Director of the Translational and Molecular Imaging Institute at Icahn School of Medicine at Mount Sinai.
"Nanotherapeutically inhibiting local macrophage proliferation is possible and we can effectively apply it to treat inflammation inside arteries. Collectively, our results demonstrate that the two-step regimen not only reduces macrophage accumulation but also reduces the expression of key genes linked to inflammation in this cell type," says senior study author Willem Mulder, PhD, Associate Professor of Radiology in the Translational and Molecular Imaging Institute at the Icahn School of Medicine at Mount Sinai.
Researchers look forward to translating their promising mice study findings to larger animal models and human clinical trials in the near future.

Explore further: New study shows non-invasive imaging tests can detect coronary artery disease long before it strikes

More information: Inhibiting macrophage proliferation suppresses atherosclerotic plaque inflammation, Science Advances, advances.sciencemag.org/content/1/3/e1400223.

New test to measure HDL cholesterol can predict cardiovascular risk

Do you want to know the risk and will your doctor offer the test?
http://www.alphagalileo.org/ViewItem.aspx?ItemId=147614&CultureCode=en
A current study by the MedUni Vienna has shown that changes to the "good cholesterol" HDL (High-Density Lipoprotein) can be associated with cardiovascular diseases: by developing a new laboratory test, scientists at the Institute of Medical Genetics and the Department of Nephrology & Dialysis (University Department of Internal Medicine III) at the MedUni Vienna have demonstrated for the first time that the presence of certain proteins in the HDL can lead to an increased risk of cardiovascular disease and mortality.
HDL (High-Density Lipoprotein) is a class of proteins that plays a key role in the body's metabolism of cholesterol. HDL causes the cholesterol to be transported to the liver, where it is broken down. This gives rise to the popular name for HDL of "good cholesterol". A team led by Thomas Weichhart (Institute of Medical Genetics), Marcus Säemann and Chantal Kopecky (both from the Department of Nephrology & Dialysis at the University Department of Internal Medicine III) have demonstrated in a study involving over 1,200 patients that the presence of two specific proteins in the good HDL can be associated with a poorer prognosis in diabetic patients who require dialysis. The study has just been published in the Clinical Journal of the American Society of Nephrology.
High HDL levels are generally regarded as the best type to have and are believed to protect against cardiovascular diseases such as heart attacks and strokes. Clinical practice currently only measures the amount of cholesterol in the HDL (known as the HDL-C) and the protective effect against future cardiovascular disease is derived from this. This relationship may hold true for the healthy population. More recent research has shown, however, that in many chronic diseases such as coronary heart disease, diabetes mellitus or in patients receiving dialysis, the quantity of HDL-C in the blood cannot be used as a prognostic marker. As a result, new methods are needed in order to better estimate the risk of cardiovascular disease.
HDL is made up of only around 20 per cent cholesterol; over 50 per cent of HDL is made up of different proteins. And it is precisely this protein composition that changes in the presence of a number of different diseases. The researchers from Vienna have already demonstrated in an earlier study that two proteins in particular, namely Serum Amyloid A (SAA) and Surfactant Protein B (SP-B), are significantly raised in the HDL of dialysis patients, and these also contribute towards HDL losing its protective effect.
Test measures "dangerous" proteins
The scientists have now developed an innovative test that can quickly and directly measure the SAA and SP-B in the HDL. The HDL protein composition in over 1,200 patients requiring dialysis was analysed using this test. The results were clear. High levels of SAA in the HDL were associated with an increased occurrence of heart attacks, while high levels of SP-B in the HDL acted as a marker for a generally increased risk of mortality. This discovery could change the evaluation of HDL. "The HDL-C value continues to remain important, however the new test will also in future allow a much more precise risk prediction for cardiovascular diseases," explain the study authors, "allowing therapy to be commenced much earlier, for example through a modified lifestyle, in order to decisively improve the overall prognosis."
The laboratory test is currently being evaluated in other patient collectives in order to confirm the results in relation to other diseases such as coronary heart disease, in which the SAA and SP-B are also raised. The laboratory test is not yet being carried out routinely; an Austrian company is however currently working on its market launch.
http://www.meduniwien.ac.at

Muscle, skin and gastrointestinal problems cause a quarter of patients with heart disease and strokes to stop treatment in HPS2-THRIVE trial

I was in the earlier trial - (AIM-HIGH) study  - that just had the niacin, no flushing blocker, I quit the trial I was in because of the exacerbation of existing excema I had on my leg. I was scratching at it until it bled.
http://www.alphagalileo.org/ViewItem.aspx?ItemId=128784&CultureCode=en
The largest randomised study of the vitamin niacin in patients with occlusive arterial disease (narrowing of the arteries) has shown a significant increase in adverse side-effects when it is combined with statin treatment.
Results from the HPS2-THRIVE study (Heart Protection Study 2 – Treatment of HDL to Reduce the Incidence of Vascular Events), including the reasons patients stopped the study treatment, are published online today (Wednesday) in the European Heart Journal [1].
Niacin has been used for decades to help increase levels of “good” HDL cholesterol and to decrease levels of “bad” LDL cholesterol and triglycerides (fats) in the blood in people at risk of cardiovascular problems such as heart disease and stroke. However, it has a number of side-effects including flushing of the skin. Another drug, laropiprant, can reduce the incidence of flushing by blocking the prostaglandin D2 receptor that is involved in the process. Therefore, the HPS2-THRIVE study investigated whether combining extended-release niacin with laropiprant (ERN/LRPT), given in addition to an LDL cholesterol-lowering statin, simvastatin, could reduce the risk of cardiovascular problems in people at high risk due to existing occlusive arterial disease.
A total of 25,673 patients from China, the UK and Scandinavia were randomised between April 2007 and July 2010 to receive either 2g of extended release niacin plus 40 mg of laropiprant or matching placebo. In addition, all participants received intensive LDL cholesterol-lowering therapy with simvastatin (with or without ezetimibe). Researchers from the Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU) at the University of Oxford (UK), who were responsible for designing and conducting the trial and analysing the results, followed the patients for an average of 3.9 years.
By the end of the study, 25% of patients taking ERN/LRPT had stopped their treatment, compared with 17% of patients taking placebo.
Jane Armitage, Professor of Clinical Trials and Epidemiology & Honorary Consultant in Public Health Medicine at the CTSU, said: “The main reason for patients stopping the treatment was because of adverse side-effects, such as itching, rashes, flushing, indigestion, diarrhoea, diabetes and muscle problems. We found that patients allocated to the experimental treatment were four times more likely to stop for skin-related reasons, and twice as likely to stop because of gastrointestinal problems or diabetes-related problems.
“We found that, in the trial as a whole, participants in the experimental arm had a more than four-fold increased risk of myopathy (muscle pain or weakness with evidence of muscle damage) compared with the placebo group. This is highly significant. It appeared that this effect was about three times greater among participants in China than those in Europe, for reasons that are not clear. In the placebo arm (i.e. those on statin-based treatment alone), the statin-related myopathy was more common among participants in China than those in Europe. Therefore – in combination with the greater effect of ERN/LRPT on myopathy in China – the excess number of cases of myopathy caused by ERN/LRPT (though low in both regions) was over ten times greater among participants in China than those in Europe (0.53 percent per year compared to 0.03 percent per year).”
Dr Richard Haynes, Clinical Coordinator at the CTSU, said: “This is the largest randomised trial of extended release niacin treatment and it provides uniquely reliable results on adverse side-effects and the ability of patients to tolerate them. Although 25 percent of patients stopped the treatment early, 75 percent continued on it for approximately four years. Currently, we are analysing the final data on the cardiovascular outcomes from the trial, and once we have these we will know whether or not the benefits of the treatment outweigh the myopathy, skin and gastrointestinal problems.”
The researchers will be presenting full results on the cardiovascular outcomes at the annual meeting of the American College of Cardiology in March and these will be published in another paper afterwards [2].
The co-principal investigator of the study, Dr Martin Landray, Reader in Epidemiology and Honorary Consultant Physician at the CTSU, said: “Previous research had suggested that improving cholesterol levels in high-risk patients might translate into a 10-15 percent reduction in major vascular events such as heart attacks and strokes. In the HPS2-THRIVE study, 3,400 of the 25,673 participants suffered a major vascular event over an average of four years of follow-up. This means the study has excellent statistical power to discover the effectiveness or otherwise of the treatment.”
In an accompanying editorial [3], Professor Ulf Landmesser, of the University Hospital Zurich (Switzerland), points out that although the study showed an increase in myopathy, it also showed that the ERN/LRPT substantially lowered LDL cholesterol and triglycerides by nearly 20%. He writes that these observations “raise important questions as to why niacin/laropiprant did not reduce major cardiovascular events”, and he wonders whether laropiprant “is really biologically inert with respect to atherosclerosis and thrombosis”.
He concludes that “niacin has failed as a valuable ‘partner’ of statin therapy in lipid-targeted approaches to further reduce major cardiovascular events in high-risk patients”. He continues: “At present, statin therapy has been clearly shown to reduce vascular events effectively and is reasonable well tolerated in most patients. We will still have to wait for the results of … ongoing studies to see whether another lipid-targeted intervention can further reduce vascular events in addition to statin therapy.”

Notes:
[1] “HPS2-THRIVE randomized placebo-controlled trial in 25 673 high-risk patients of ER niacin/laropiprant: trial design, pre-specified muscle, and liver outcomes and reasons for stopping study treatment”, by Richard Haynes, Lixin Jiang, Jemma C. Hopewell, Jing Li, Fang Chen, Sarah Parish, Martin J. Landray, Rory Collins, and Jane Armitage, The HPS2-THRIVE Collaborative Group. European Heart Journal. doi:10.1093/eurheartj/eht055
[2] In December 2012 the pharmaceutical company Merck, which manufactures ERN/LRPT under the trade name Tredaptive and which funded the HSP2-THRIVE study, issued a statement saying the trial had failed to meet its primary endpoint and that “the combination of extended-release niacin and laropiprant to statin therapy did not significantly further reduce the risk of the combination of coronary deaths, non-fatal heart attacks, strokes or revascularizations compared to statin therapy.” ERN/LRPT is not approved for use in the USA, and on January 11, Merck announced that it was “taking steps to suspend the availability of TREDAPTIVE™ (extended-release niacin/laropiprant) tablets worldwide.”
[3] ”The difficult search for a ‘partner’ of statins in lipid-targeted prevention of vascular events: the re-emergence and fall of niacin”, by Ulf Landmesser. European Heart Journal. doi:10.1093/eurheartj/eht064