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.... At 2 years, niacin therapy had significantly increased the median HDL cholesterol level from 35 mg per deciliter (0.91 mmol per liter) to 42 mg per deciliter (1.08 mmol per liter), ...
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As I keep saying, there's a difference between statistical significance (a mathematical concept with an arbitrary difintion, usually p<0.05) vs clinical significance, ie- is this something that really makes a difference in practice?
Theories are neither right nor wrong, but are judged by their usefulness in accounting for known observations and ability to predict future results.... Cf- Newton's theory of gravity-- good enough to put a man on the moon & get him back, but not good enough to predict the orbit of Mercury. Einstein's theory will do that, but is way too detailed to be useful for moon flights. Einstein is more "correct" but Newton is more "useful."
Right or wrong, it's convenient to consider LDL as trash placed at the curb for pick-up and HDL the number of garbage trucks available for duty-- no matter how much or how little trash there is, the streets will be dirty unless there's enough trucks to get the job done. That's where the total C/ HDL ratio becomes important vs the lowest quintile of HDLs where there's never enough trucks, so to speak.
Those with HDL< 25 or so can expect earlier, more severe problems with arterosclerosis. Those with HDL> 25 all have about the same risk in practical terms. We're splitting hairs claiming there's a real difference among the higher four quintiles....Unfortunately, there's no good treatment for the very low HDL, therefore we need to emphasize the other things that we can do something about-- attention to close control of DM, avoid smoking, exercise regularly and maintain a high index of suspicion- jumping in with early stress testing &/or angiography.
This classic graph is actually labelled incorrectly-- the "baseline risk" (1.0) should be level with the top of the bar at ldl 100/ hdl 85. As you can see, only the back line of bars (hdl 25) and the ldl 220/hdl45 are significantly higher than the baseline risk. (You gotta die of something.)
Last edited by guidoLaMoto; 10-17-2023 at 03:03 PM..
As I keep saying, there's a difference between statistical significance (a mathematical concept with an arbitrary difintion, usually p<0.05) vs clinical significance, ie- is this something that really makes a difference in practice?
Theories are neither right nor wrong, but are judged by their usefulness in accounting for known observations and ability to predict future results.... Cf- Newton's theory of gravity-- good enough to put a man on the moon & get him back, but not good enough to predict the orbit of Mercury. Einstein's theory will do that, but is way too detailed to be useful for moon flights. Einstein is more "correct" but Newton is more "useful."
Right or wrong, it's convenient to consider LDL as trash placed at the curb for pick-up and HDL the number of garbage trucks available for duty-- no matter how much or how little trash there is, the streets will be dirty unless there's enough trucks to get the job done. That's where the total C/ HDL ratio becomes important vs the lowest quintile of HDLs where there's never enough trucks, so to speak.
Those with HDL< 25 or so can expect earlier, more severe problems with arterosclerosis. Those with HDL> 25 all have about the same risk in practical terms. We're splitting hairs claiming there's a real difference among the higher four quintiles....Unfortunately, there's no good treatment for the very low HDL, therefore we need to emphasize the other things that we can do something about-- attention to close control of DM, avoid smoking, exercise regularly and maintain a high index of suspicion- jumping in with early stress testing &/or angiography.
This classic graph is actually labelled incorrectly-- the "baseline risk" (1.0) should be level with the top of the bar at ldl 100/ hdl 85. As you can see, only the back line of bars (hdl 25) and the ldl 220/hdl45 are significantly higher than the baseline risk. (You gotta die of something.)
Sticking with the newer theories the study can be explained this way,
If one takes niacin to raise an HDL cholesterol from 35 mg/dL to 42 mg/dL one sees not much happen. If one were to be insulin resistant explaining the low 35 mg/dL and if they do lifestyle changes, diet and exercise and reduce that insulin resistance and bring it up to 42 mg/dL then it would be postulated to reduce heart risk. It's not because they raised their HDL but the way they did it through a known risk factor.
"Study challenges “good” cholesterol’s role in universally predicting heart disease risk
November 21, 2022, 2:00 PM EST
Lower levels of HDL cholesterol were associated with increased risks for heart attacks in white but not Black adults, and higher levels were not protective for either group
A National Institutes of Health-supported study found that high-density lipoprotein (HDL) cholesterol, often called the “good cholesterol,” may not be as effective as scientists once believed in uniformly predicting cardiovascular disease risk among adults of different racial and ethnic backgrounds.
The research, which published in the Journal of the American College of Cardiology external link , found that while low levels of HDL cholesterol predicted an increased risk of heart attacks or related deaths for white adults – a long-accepted association – the same was not true for Black adults. Additionally, higher HDL cholesterol levels were not associated with reduced cardiovascular disease risk for either group.
However, the study was the first to find that lower HDL cholesterol levels only predicted increased cardiovascular disease risk for white adults. It also expands on findings from other studies showing that high HDL cholesterol levels are not always associated with reduced cardiovascular events. The REGARDS analysis was the largest U.S. study to show that this was true for both Black and white adults, suggesting that higher than optimal amounts of “good” cholesterol may not provide cardiovascular benefits for either group."
How does one justify TC/HDL ratios with those findings? You can't always go by HDL. It is the ashtray and not the cigarette.
ApoB testing may reveal patients at risk of heart disease missed by cholesterol tests: study
Nick Paul Taylor
Mar 6, 2023
“Data suggest that these particle numbers increase risk to a greater extent than just cholesterol levels alone,” Dr. Jeffrey L. Anderson, Intermountain Health cardiologist, said in a statement. “ApoB could help us identify a population of patients with normal or even low LDL numbers but who are at higher risk and should be more aggressively treated.”
The bottom line is this, you reduce clinical risk factors like hypertension, smoking, insulin resistance and laboratory indicators specifically ApoB levels. If one targets ApoB levels then that is what should be done. Reduce clinical risk factors and reduce ApoB with medication. That is the latest research and the perspective of lipid research. I recognize the gap between clinical practice and research. I rarely fall for the hype associated with research. I can tell you that ApoB for the last forty years has always been assumed as the preferred clinical lab test to assess cardiac risk. That has only gotten stronger over time.
Thanks for this discussion, Med Lab Guy and Guido.
I am a little worried because for the last 25 years I have had freakishly high HDL levels, like 97. Doctors thought it was a good thing..cardioprotective, saying I would likely never have heart issues.
But now that there are a couple new studies saying high HDL is associated with dementia…seems to be associated with increased risk by 27%, it makes me anxious because I fear dementia more than cancer or heart problems.
I have no idea why my HDL is so high. Don’t know if it’s genetic. My parents lived to be 90 and 93, but didn’t have much testing for stuff like cholesterol so far as I know. I exercise daily and have a healthy diet. Should I start eating junk to lower my HDL?
Last edited by jazzcat22; 01-06-2024 at 04:17 PM..
Thanks for this discussion, Med Lab Guy and Guido.
I am a little worried because for the last 25 years I have had freakishly high HDL levels, like 97. Doctors thought it was a good thing..cardioprotective, saying I would likely never have heart issues.
But now that there are a couple new studies saying high HDL is associated with dementia…seems to be associated with increased risk by 27%, it makes me anxious because I fear dementia more than cancer or heart problems.
I have no idea why my HDL is so high. Don’t know if it’s genetic. My parents lived to be 90 and 93, but didn’t have much testing for stuff like cholesterol so far as I know. I exercise daily and have a healthy diet. Should I start eating junk to lower my HDL?
One has to be careful about associations because of confounding variables. There is what is called vascular dementia that has vascular components to it and then there's other sources of dementia. The cholesterol theory tries to explain the importance of cholesterol in causing blood vessel disease and occlusion of the lumen. This causes diminished flow and easier to occlude with plaque break-off and thrombosis.
The study you cite did find an association between High HDL cholesterol but also found,
"Associations remained significant after adjusting for covariates including age, sex, country of enrolment, daily exercise, education, alcohol consumption, weight change over time, non-HDL-C, HDL-C-PRS, and APOE genotype.
Interpretation
In a population of initially-healthy older adults aged ≥75 years, high HDL-C levels were associated with increased risk of all-cause dementia."
Those findings in my opinion suggest some other mechanism besides the cholesterol theory. There was no strong correlation with non-HDL-C cholesterol levels which tend to be the highest predictor of conventional risk for coronary and vascular events. The increased dementia was found in all cause dementia that goes beyond vascular dementia. Dementia is separate from vascular disease.
This would be more of a laboratory marker highlighting an association rather than a cause. In essence if it is simply a marker then lowering it would not eliminate the risk. If the high HDL were causing the risk then lowering it would be beneficial.
There needs to be more research on that front to answer that question.
There is a dilemma right now though and it is also playing out in other areas of lipid research. There is an interrelationship between lipid particles. Newer studies in research have determined that lipid particle number is more predictive than other parameters. As I mentioned an increased HDL may not be predictive of future vascular disease. The association was a low HDL is associated with such events in which genetics play a role. The LDL concentration may not be predictive or one can be mislead simply going by the overall concentration of LDL if one does not go by the particle number instead. They same with high HDL is implied. I would like to see ApoB levels in those patients with high HDL levels in those with dementia. The indirect evidence right now is that the levels would be normal without implied risk of the regular vascular complications seen in those with high lipid particle number.
Now as stated in another thread on statin use the topic of metabolic syndrome has come up. Metabolic syndrome is a clinical risk factor for vascular disease. The diagnostic criteria for metabolic syndrome are a high triglyceride level and a low HDL level. Some have postulated that blood triglyceride levels are the culprit causing all of the problem and not the cholesterol. The hypothesis is if one lowers triglyceride by any means then the risk will go away. It isn't that easy to prove based solely on the common lipid panel.
Metabolic syndrome does cause a high triglyceride level but it also causes an increase in LDL concentration or lipid particle number. The lipids are interconnected and thus one does not assume triglycerides to be an independent risk factor. It is assumed to be a marker for metabolic syndrome but triglycerides are not assumed to be causative. It is a marker for a clinical risk factor. Renal failure is also a clinical risk factor but no one is going to say that the creatinine in the blood is causing vascular disease.
So what I am saying is that when it comes to lipids some are markers and for right now particle number is thought to be causative. There is confounding interrelationships that need to be separated when coming to conclusions.
There might be some other genetic component at play with patients who have high HDL and come down with dementia. The correlation is not 100%. Some people with a high HDL will come down with it. Most people without high HDL will succumb to it. High HDL levels are not that common.
I presume she had high cholesterol which is why your SIL was put on statins. Normally one wants to address all issues pertaining to risk which includes clinical risk factors and if she had low HDL then metabolic syndrome usually causes a low HDL with a high triglycerides and so those issues should be addressed to reduce risk. If she has high blood pressure or smokes or etc then those issues should be addressed. What can't be addressed via lifestyle issues are genetic factors that cause a low HDL and coronary risk.
You finally mentioned metabolic syndrome, but you still refuse to say that metabolic syndrome is the MOST common reason for heart disease and stroke in modern societies.
Anyone with low HDL and high triglycerides should be suspected of having metabolic syndrome, and statins WILL NOT help them, and could make it worse.
Why try to minimize this serious health problem that maybe half of Americans have or are heading towards?
All those details about different types of cholesterol are not helpful for the most people. The first thing any MD should do is check for metabolic syndrome (or cigarette smoking), and if that is not the cause, THEN go on to other ideas.
But what seems to happen more often is an assumption that the cause is genetic and drugs are needed. Oh your father and your grandfather had heart disease? Then it must be genetic. NO. Maybe there is a genetic vulnerability, but it's also likely that the father and grandfather had metabolic syndrome.
The emphasis on genetics is good for the statin makers. It also means less work for the patient because they can take a pill instead of working on their lifestyle.
And it is wrong to disparage these ideas as "holistic." An approach can consider the system as a whole, and STILL be scientific and evidence based.
You finally mentioned metabolic syndrome, but you still refuse to say that metabolic syndrome is the MOST common reason for heart disease and stroke in modern societies.
Anyone with low HDL and high triglycerides should be suspected of having metabolic syndrome, and statins WILL NOT help them, and could make it worse.
Why try to minimize this serious health problem that maybe half of Americans have or are heading towards?
All those details about different types of cholesterol are not helpful for the most people. The first thing any MD should do is check for metabolic syndrome (or cigarette smoking), and if that is not the cause, THEN go on to other ideas.
But what seems to happen more often is an assumption that the cause is genetic and drugs are needed. Oh your father and your grandfather had heart disease? Then it must be genetic. NO. Maybe there is a genetic vulnerability, but it's also likely that the father and grandfather had metabolic syndrome.
The emphasis on genetics is good for the statin makers. It also means less work for the patient because they can take a pill instead of working on their lifestyle.
And it is wrong to disparage these ideas as "holistic." An approach can consider the system as a whole, and STILL be scientific and evidence based.
Your interpretations are way off. I don't understand what you are saying most of the time. Again there's no common playing ground.
Metabolic syndrome MS is a medical diagnosis based on the diagnostic criteria and you are saying that we minimize it and ignore it.
Every site on the web and practice guidelines state to treat it with statins and other medications when applicable because there are several differing metabolic expressions and possible medication in treating the high glucose, high trigs, high cholesterol and high blood pressure So you lost me there.
Statins lower triglyceride levels and cholesterol levels and only slightly increase HDL levels. There is dispute among researchers involving triglycerides. Some question whether it is an independent risk factor.
As far as modern cholesterol theory let me quote an article from
The Journal of Lipid Research
J Lipid Res. 2018 Jul; 59(7): 1266–1275.
Hypertriglyceridemia and cardiovascular risk: a cautionary note about metabolic confounding
Triglycerides are the conventional tool to measure VLDLs, whereas LDL cholesterol (LDL-C) is the conventional tool to measure LDLs. Multiple epidemiological studies, including a series of genetically based analyses, have demonstrated that cardiovascular risk is related to triglycerides independently of LDL-C, and this has led to a series of new therapeutic agents designed specifically to reduce plasma triglycerides. The triglyceride hypothesis posits that increased levels of triglycerides increase cardiovascular risk and decreasing plasma triglycerides decreases cardiovascular risk. In this work, we will examine the validity of the triglyceride hypothesis by detailing the biological complexities associated with hypertriglyceridemia, the genetic epidemiological evidence in favor of hypertriglyceridemia, the evidence from the fibrate randomized clinical trials relating triglycerides and clinical outcomes, and the completeness of the evidence from the initial studies of novel mutations and the therapeutic agents based on these mutations that lower triglycerides. Because of the multiple metabolic links between VLDL and LDL, we will try to demonstrate that measuring triglycerides and LDL-C alone are inadequate to document the lipoprotein profile. We will try to demonstrate that apoB must be measured, as well as triglycerides and cholesterol, to have an accurate estimate of lipoprotein status.
Mendelian randomization of blood lipids for coronary heart disease (39)
The authors concluded that LDL-C was causal for cardiovascular risk; triglycerides were also likely causal, but HDL-C was unlikely to be causal. Once again, the conclusions regarding triglycerides and cardiovascular risk were provisional. Moreover, apoB was not included in the analysis.
DOES LOWERING PLASMA TRIGLYCERIDES WITH FIBRATES REDUCE CARDIOVASCULAR RISK? EVIDENCE FROM THE FIBRATE RANDOMIZED CLINICAL TRIALS
In summary, the clinical benefit of fibrate therapy was variable; ischemic events were reduced significantly in only three of the seven trials. However, in the six fibrate trials in which they were measured, there was a robust lowering of triglycerides. Thus, the triglyceride response to fibrates was consistent, whereas the clinical response was not. Moreover, with the exception of the VA-HIT trial, the degree of benefit was consistent with the benefit that would be predicted from the absolute reductions in LDL-C or non-HDL-C or apoB. These results argue against the triglyceride hypothesis: namely that when triglycerides are elevated, cardiovascular risk is elevated and that lowering triglycerides will, in itself and by itself, reduce cardiovascular risk and produce clinical benefit. On the other hand, this failure of the triglyceride hypothesis suggests an alternative one: namely, the apoB hypothesis, which states that the benefit of fibrate therapy is primarily due to lowering of the apoB atherogenic lipoproteins, which is reflected in lowering of plasma apoB. Figure 3 compares the overall effects of statins and fibrates on total plasma apoB, VLDL apoB, and LDL apoB (14–16, 49). Statins substantially lower both VLDL and LDL apoB. Hence, they substantially lower plasma total apoB. By contrast, fibrates substantially lower VLDL apoB, but only modestly reduce LDL apoB. The effect of statins and fibrates on VLDL apoB is similar, but their effects on LDL apoB are not. Fibrates are used in hypertriglyceridemic patients in whom absolute levels of VLDL apoB tend to be higher than normal. The net effect, therefore, is a modest to moderate lowering of total plasma apoB. The apoB hypothesis would account for why benefit from statin therapy is robust, whereas benefit from fibrate therapy is marginal and inconsistent because only if VLDL apoB accounts for a significant proportion of total apoB will there be a sufficient reduction in apoB to translate into clinical benefit."
I did not take the information from the original post from this article as a source. It does include all the points that are commonly accepted by present day current lipid researchers. This is where the thinking is at.
The position I take is evidenced based. discussing theory then will all have opinion. Your position that one can not treat MS with medication and nothing works is simply bizarre and opinion. To say that only genetic lipid disorders are treatable is more than bizarre. Doctors treat the patient in front of them or watch them die. They suggest lifestyle changes but that is all up to the patient.
The reason metabolic syndrome was brought up was one of confounding variables with lipid research that might apply to high HDL levels. Mandelian randomizaiton analysis was mentioned in the original post here. It separates or tries to separate variables. One should use ApoB to see if one can separate the variable in metabolic syndrome and in high HDL levels and dementia.
All of the cardiovascular risk calculators out there online do not include data entry for triglyceride levels nor for glucose level. They are not there to detect MS. It is there to detect risk. It is a clinical risk factor and not a laboratory risk factor included in calculators. It is a risk factor like renal failure.
You keep on invoking MS as if it is the only thing out there. You never mention PCOS in women who also have insulin resistance with cardiovascular risk. It is a clinical risk factor. Testosterone levels are not included in the calculators. Those are separate.
"Statins are lipid-lowering agents with pleiotropic actions. Experts have proposed that in addition to improving the dyslipidaemia associated with polycystic ovary syndrome (PCOS), statins may also exert other beneficial metabolic and endocrine effects, such as reducing testosterone levels."
Last edited by Medical Lab Guy; 01-06-2024 at 06:02 PM..
body makes chol because it needs to. chol is one of the most important substances in the body - it's converted to all kinds of vital biochems/hormones/etc
taking statins is counterproductive -- it's treating the marker of health problems with chemicals, and not focusing on the cause/actual problem. bonus -- horrific short and long term side effects
body makes chol because it needs to. chol is one of the most important substances in the body - it's converted to all kinds of vital biochems/hormones/etc
taking statins is counterproductive -- it's treating the marker of health problems with chemicals, and not focusing on the cause/actual problem. bonus -- horrific short and long term side effects
Right. For most people, high cholesterol is not the cause, and statins will make their metabolic syndrome worse, plus cause known and unknown bad side effects.
Your interpretations are way off. I don't understand what you are saying most of the time. Again there's no common playing ground.
Metabolic syndrome MS is a medical diagnosis based on the diagnostic criteria and you are saying that we minimize it and ignore it.
Every site on the web and practice guidelines state to treat it with statins and other medications when applicable because there are several differing metabolic expressions and possible medication in treating the high glucose, high trigs, high cholesterol and high blood pressure So you lost me there.
Statins lower triglyceride levels and cholesterol levels and only slightly increase HDL levels. There is dispute among researchers involving triglycerides. Some question whether it is an independent risk factor.
Yes, the problem must be that you do not understand what I am saying. I have made it as clear and simple as possible, so I don't know why you can't understand it.
Treating metabolic syndrome with statins MAKES NO SENSE, because statins raise blood glucose and therefore make metabolic syndrome worse!
Metabolic syndrome is known to result mostly from the modern industrial lifestyle. If patients stop following that lifestyle, they can reverse metabolic syndrome, especially if caught early.
How is any of this hard for you to understand? You are entirely focused on drugs. There is nothing unconventional or controversial or "alternative" about what I am saying. Metabolic syndrome is recognized in mainstream medical journals. Its cause is understood.
As others have been trying to explain to you, high cholesterol is, most often, a SIGN of metabolic syndrome not a cause. Low HDL and high triglycerides, rather than simply high cholesterol, might be a better way to diagnose metabolic syndrome.
All of the cardiovascular risk calculators out there online do not include data entry for triglyceride levels nor for glucose level. They are not there to detect MS. It is there to detect risk. It is a clinical risk factor and not a laboratory risk factor included in calculators. It is a risk factor like renal failure.
And you don't think that is a problem? They calculate risk the same way regardless of whether the high cholesterol is from a genetic defect or from lifestyle. You don't think those 2 possibilities should be treated differently?? In one type of patient, the small minority, high cholesterol is the cause and statins address the cause (well there must be deeper causes but they are not yet known). In the other type of patient, the great majority, high cholesterol is a RESULT of metabolic syndrome, and lowering cholesterol with drugs has no benefit, and is harmful.
Quote:
Originally Posted by Medical Lab Guy
You keep on invoking MS as if it is the only thing out there. You never mention PCOS in women who also have insulin resistance with cardiovascular risk. It is a clinical risk factor. Testosterone levels are not included in the calculators. Those are separate.
I naver said MS is the only thing out there!! But it is the MOST COMMON thing out there! Why can't you get that. You think PCOS is as common as metsym? That is a crazy idea.
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