#182

Buy some Metformin and hand it out on the street…more of a direct contribution to public health.

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#183

At first glance (Table), the difference between the 2 groups in terms of hard end points seems impressive (157 vs 83 for placebo and rosuvastatin, respectively). But are these differences plausible? Although an “unequivocal reduction in cardiovascular mortality” was announced in March 2008 as the main justification for the premature trial termination,19,20 the absence of cardiovascular mortality data in the published article is striking. One may infer from the Table—although not indicated in the text—that the total number of fatal myocardial infarctions was 9 in the rosuvastatin group (the difference between 31 “any myocardial infarctions” and 22 “nonfatal myocardial infarctions”) and 6 (68 − 62) in the placebo group. Similar calculations for fatal stroke (the difference between “any stroke” and “nonfatal stroke”) show 3 (33 − 30) in the rosuvastatin group and 6 (64 − 58) in the placebo group.

Cardiovascular mortality (fatal stroke plus fatal myocardial infarction) would therefore be identical in both groups (12 vs 12). Such a lack of effect on cardiovascular mortality associated with a strong effect on nonfatal complications strongly suggests a bias in the data set and should have led to the continuation of the trial rather than to its premature ending. Other inconsistencies add to the confusion.

#184

First, the ratio of fatal myocardial infarction (9 for rosuvastatin and 6 for placebo) to nonfatal myocardial infarction (22 and 62) is incredibly low, especially in the placebo group. Mortality from acute myocardial infarction is a very important issue in cardiology. The data would suggest that the hearts of the JUPITER patients were unexpectedly—and inexplicably—highly resistant to acute ischemia and infarction. The worst consequence of low myocardial resistance to ischemia is death, often sudden cardiac death (SCD). Myocardial infarction–related death, the “case-fatality rate” in epidemiological reports, is usually very high and is known, thanks to the World Health Organization’s MONICA study, in many populations with very different risks.28 Out of 100 patients who have a myocardial infarction, an average of 50 die immediately—usually out of hospital—or within the 3 to 4 weeks that follow, and almost never fewer than 40 out of 100, even in populations with low cardiovascular mortality, for example in Japan and around the Mediterranean sea.28 In the JUPITER trial, the case-fatality rate in the placebo group was incredibly low: 8.8%, a clinical inconsistency that suggests a major flaw in the study. Moreover, the case-fatality rate in the rosuvastatin group was 29%. This rate was significantly different from that in the placebo group (Fisher exact test, P = .01) and more consistent with (though still lower than) the range reported in the MONICA study.28 Another dilemma is raised by this figure as it would imply that the use of rosuvastatin tripled the case-fatality rate. This figure is not credible.

Sudden cardiac death actually is the simplest and most reliable diagnosis in cardiology because, contrary to myocardial infarction, there is no need for biologic and/or electrocardiographic criteria. It is defined as a death occurring within 1 hour after the first symptoms of heart attack—or as an unwitnessed death.30 It is therefore very surprising that no SCD is reported in the JUPITER trial because SCD usually represents about 65% to 70% of total cardiac mortality.31 As previously underlined,32 the way SCD is reported—or not reported—may be a good indicator of the quality of the methods used in a trial.

#185

That would be easier to do if he would stop posting under more than one username and having conversations and arguments with himself. But I try.

1 Like
#186

Was going to suggest looking at John Kastelein’s interview with Peter Attia too.

1 Like
#187

so do we keep taking statin or not?

#188

In MR studies the model is pretty simple and purely linear. They can’t fit J or U shaped curves.
The causal effect is the slope of that line.
In that study, the causal effect is:

Causal effects are log odds ratios for coronary artery disease per 1 standard deviation increase in the risk factor.

I googled for a value of the APOB standard deviation and found around 25mg/dl so here are the odd ratios for a given increase of APOB in mg/dl

Diff APOB (mg/dl) Odd Ratio
-20 0.69
-10 0.83
0 1.00
10 1.20
20 1.45

Again this is a purely linear fit and will not apply to low or high values. It’s the slope around the average.

2 Likes
心血管健康
#189

This is a really interesting and relevant statistical argument. If i can add to this: if our understanding/measurement of correlations of LDL to CVD are at their heart statistical averages of the health (and metabolic health), haven’t these averages themselves been changing with time in the population? i.e. are the “average” people (at least for the subjects of these studies) becoming less healthy over time? So perhaps we are measuring an artifact of people being less healthy? (Or biologically older than their chronological age?)

Certainly many of you have strongly pointed out that CVD mortality is increasing only in non-US populations (and is declining in the US), although i might argue this, too, is an artifact of much better trauma/acute care in which something as simple as a cheap defibulator available in many more places can lower this number.

(Again, not arguing that there is some proven causal effect of LDL with CVD, only that perhaps when you are young and/or healthy perhaps this correlation is very weak, and when you are “old” and less-healthy there is a strong correlation?)

#190

He did say “sane doctor”.

#191

I hope this will help some of us — i haven’t yet measured my ApoB even though my LDL is high. I heard a podcast in which I think it was Thomas Dayspring mentioned that you can fairly accurately approximate ApoB from a basic lipid panel (which is how he decides whether to get more advanced lipids tests). He did NOT mention this specific paper; i looked it up myself so all errors are likely mine….

The regression equation Apo B = 25.199 + 0.266 (LDL) + 0.062 (triglycerides level [TGL]) + 0.248 (non-high-density lipoprotein cholesterol) was the best predictor of Apo B when directly measured LDL-C was used.

For me: 25.199 + 43.64 + 3.97 + 4.96 = 77.769
So is this ok?

Normal levels of ApoB-100 in adults are less than 100 mg/dL. Your risk is high if you have a result greater than 110 mg/dL .
Apolipoprotein B-100 - Health Encyclopedia - University of Rochester Medical Center.

2 Likes
#192

Apparently not you! :slight_smile:

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#193

So what is the baseline? — i think your above figures call 1.26-1.39 the ApoB reference range, so that is stdev=0? How does that relate to the ApoB of 76 I calculated from the regression model? Obviously they aren’t in the same units, but which are normal units for discussing ApoB so i can compare them?

Also i must have missed part of the discussion above: the charts suggest the lower TG (triglycerides) the better. But show a u-shaped mortality for (based on the reference range; no idea if the “reference range is in the 5th percentile of the overall population so is actually massively low). I thought ApoB was similarly “the lower the better”?

it’s not what the plots show.
Very low TC is always bad for all cause mortality for all age groups.
Very low TC is trending bad for CVD mortality for all age groups though not statistically significant.
So if you have a too low TC you die sooner.

For APOB there is no significant effect for very low, low or medium levels.
Very low APOB is trending bad though not statistically significant.
High and very high APOB is bad.
So keep your APOB low of medium. Extremes are bad.

In all cases TG is bad and low HDL (APOA1) is bad.

The Wild Science of Growing Younger (Worth)
#194

Interesting opinion: Youtube: You WANT High LDL Cholesterol (Your MD Needs To See This)

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According to Dr. Anthony Jay, TC in the range 180-280 mg/dl minimize hazard ratio and normalizes hormones.

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#195

I really like him! I don’t know if he’s right, but he makes me feel good.

I’m doing DMSA every couple weeks now, beta cyclodextrin, and colchicine. And my cholesterol is 260. I’m never sick. My son just got covid, wife under the weather, I’m like always feeling great.

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#196

What’s your family history of cardiovascular disease?

#197

My mother’s cholesterol has been 260 or so for as long as I remember. She didn’t take statins bc she didn’t believe in them. She’s 92 now and still lives independently and doesn’t have any problems with her heart.

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#198

Grandparents all died of cancer, but lived long. Mom was type 1 diabetic and took shots for nearly 50 years, got a triple bypass a few years before the end. Dad had ALS, prostate cancer and got a quad bypass 10 years before the end. Died of prostate cancer moving to the bones.

I got a bad CAC and that’s what got me into all this health stuff. I found out it’s a very interesting topic.

4 Likes
#199

Yes, so much we can do - and so much more we likely will be able to do over the next decade and few - if we at that time still remain in good shape especially

With a high cac would consider not staying at high Apo B / LDL levels

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#200

The idea is that beta cyclodextrin selectively takes out the sLDL and leaves the rest of the LDL alone. It does a bunch of other good stuff too, but I like the idea of not throwing out the baby with the bathwater.

Colchicine is brilliant, stopping the inflammation.

I think the whole problem probably starts, when it can, in people with high Lead, Iron, Cadmium and there are ways to lower these safely. DMSA keeps heavy metals out of the brain too, which EDTA does not. Doing it slowly over a long time is a really good way to go.

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#201

Look at Mileage

Large LDL particles seem to have especially low hazard ratios

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