A lot to unpack here to be honest, but I think what we should be vary of is basing medical decisions solely on feeling and body signals, this is subject to placebo and nocebo, and it’s easy to trick oneself into believing something is harmful when it’s actually not, or something is beneficial when it’s actually harmful. Of course if you have an obvious side effect of a drug or treatment or of great magnitude then that’s important to consider especially if it has been reported previously.
Usually I like to look at the actual clinical trial where one group has had the placebo and another the drug, that way it’s possible to see how people differ from the placebo effect in terms of side effects and beneficial effects. Supplements don’t have clinical trials in most cases or they are poorly done or too small to be useful because of cost considerations. And of course the most important risk factors as far as I know in your case isn’t something that can be felt, like apoB / LDL-C.
Lp(a) is new and a typical doctor isn’t going to know how to treat it and prevent complications from CVD, neither would they for radical CVD prevention. If you can’t find a specialist familiar with reducing risk with Lp(a) and overall ASCVD prevention, I recommend podcasts with Peter Attia on these two topics. I’m sure others in this thread have good sources. Best of luck.
Thanks I have Attia’s book and will soon be under a specialist’s management. My doctor did say he has had quite a few patients bring their cholesterol down with bergamot and said it is worth a try- retest in a few months. In Australia they are not keen to use statins unless its very high cholesterol. I have done heaps and heaps of reading, watched videos etc so am pretty informed now. Will see what the specialist advises.
Again, it goes back to that “well, something has to kill you, so I might as well let it be this thing you already have”, which isn’t a smart approach IMO.
Have we ever discussed these studies showing that testosterone reduces Lp(a), and reduces it quite significantly, up to 37% in one of the studies below:
makes sense to me - low estrogen affects thyroid function in women which adversely affects lipid regulation and surely impacts Lp(a) levels in post menopasue. I had no issues a few years ago my cholesterol and thyroid were good.
Interesting. I would however caution, that while something might lower Lp(a), it may net out to not be worth it. That’s true of many aspects of physiology. Focusing on just one aspect of a function, is how we can be led astray by mechanistic speculation. Parkinson’s Disease patients have frequently lower LDL, but we wouldn’t want to induce PD (by f.ex. destroying the substantia nigra), in order to get better LDL levels. Alzheimer’s patients have less cancer, but we wouldn’t want etc.
So OK, increasing testosterone might lower Lp(a), but what matters is not an isolated mechanistic effect, but outcomes. What is the net?
For example, I have sky high Lp(a), but also very good level of testosterone for my age. I have no intention of driving my testosterone sky high in hopes of some Lp(a) lowering. I don’t think it would net out well for me.
Now, perhaps for those who have suboptimally low T, supplementing might be a great idea, and lowering of Lp(a), a nice bonus. So I’m not opposed to HRT in the right context, but it’s worth looking at the big picture.
Ultimately it’s always about how it impacts outcomes, including all cause mortality. If adding T can be a positive, great!
I totally agree with you- dont want HRT as I already have an acoustic neuroma treated 6 years ago and who knows how HRT and especially progesterone might affect tumor regrowth. My Lp(a) is 187 but I feel good am very active. I cannot seem to tolerate even a small dose of levothyroxine so for now I am just focussing on being sensible re diet, sleep, stress levels and moderate exercise.
Totally agreed. For a lot of guys, exogenous testosterone will have a bunch of other effects; obviously reducing your HPTA, hormones like LH and FSH, but also generally increases water retention, blood pressure and hematocrit, making your heart work a lot harder. Of course, it also has clear benefits like improving bone density, positive effects on mood etc. So as you say, each person needs to look at the bigger picture and decide for themselves. Even though my Lp(a) is high, I wouldn’t start TRT to deal with it.
Lipoprotein(a) levels and what to do about them is the subject of this forum. My Lp(a) level runs about 160 nmol/L … so higher than I would like, but I don’t want to pay for PCSK9i etc meds. I recently came across an interesting 2021 JACC article (hsCRP Modifies the Cardivascular Risk of Lp(a) a Multi-Ethnic Study of Atherosclerosis by Wei Zhang, MD et al JACC 2021,V78,1083-1094 ) which concludes:
Lp(a) associated ASCVD risk is observed only with concomitant elevation of hsCRP >2.
The implication is that those with elevated Lp(a) should do all they can to lower their hsCRP.
Aside from exercise, good diet and appropriate supplements - Vitamin C and Lysine if you believe Linus Pauling, Statins will lower your hsCRP, at much less cost than PCSK9i etc meds. Note that the anti-inflammatory benefit of Statins is likely why they have been reported to have greater benefit than their cholesterol lowering effect would suggest.
“Correlations between inflammatory markers and lipoprotein measures are depicted in Supplementary data online, Figure S2 . HsCRP had a weak positive correlation with VLDL (ρ: 0.17 to 0.25) and LDL subclasses (ρ: 0.09 to 0.13). In contrast, glycoprotein acetyls displayed moderate positive correlations with VLDL (ρ: 0.43 to 0.62) and LDL (ρ: 0.37 to 0.46) subclasses. Lp(a) showed no correlation with either inflammatory biomarker (ρ: 0.00 to 0.03).”
Quote:
“In the variance-standardized model, 1-SD higher (72 nmol/L) Lp(a) count was associated with a 20% higher risk of CAD (HR 1.20, 95% CI 1.18–1.22, Figure 4 and Supplementary data online, Figure S4 ). This association remained essentially unchanged after adjusting for apoB-P (HR 1.18, 95% CI 1.16–1.20). When expressed as a 100 nmol/L increase, the per-particle risk of CAD associated with Lp(a) was 3.3-fold higher risk than the per-particle risk for an equimolar increase in apoB. We found no evidence of a multiplicative interaction between Lp(a) and apoB-P (P = .52). Sensitivity analyses involving adjustment of Lp(a) for conventional apoB-P measurements yielded similar findings to the main analysis (see Supplementary data online, Table S12 ).”
As your ApoB reference points out, hsCRP levels do not alter measured levels of Lp(a)
No surprise there.
Alternatively the JACC reference implies that hsCRP levels change the reactivity of the Lp(a) moieties present.
Lower hsCRP implies less reactive Lp(a), not quantitatively less Lp(a)
Less reactive Lp(a) implies lower ASCVD risk.
Here’s a commentary on the Zhang study you referenced:
High-Sensitivity CRP Modifies the CV Risk of Lp(a)
"Perspective:
The findings are derived from baseline lipids and limited to low-risk persons without CVD with an average age of 62 years who had an annual CVD event rate including strokes of about 1% over nearly 14 years. Since the findings were independent of other known CVD risk factors, when either Lp(a) or hsCRP is elevated, it is reasonable to assess the other, and when both are elevated, consider more aggressive ASCVD management. But much needs to be done prior to incorporating the strategy into guidelines."
" Question Is higher lipoprotein(a) (Lp[a]) associated with increased cardiovascular risk independent of baseline high-sensitivity C-reactive protein (hs-CRP) level?
Findings This cohort study found in both a primary prevention population (UK Biobank) and secondary prevention populations (FOURIER [TIMI 59] and SAVOR-TIMI 53), higher Lp(a) was associated with increased risk of major adverse cardiovascular events, myocardial infarction, and peripheral artery disease regardless of baseline hs-CRP level.
MeaningIn both primary and secondary prevention populations, higher Lp(a) was associated with increased cardiovascular risk independent and regardless of hs-CRP*."
IL-6 may be even more important in this context than hsCRP:
Inflammation, Lp(a) and cardiovascular mortality: results from the LURIC study
“Participants were predominantly male, with a mean age of 62.6 years. Extremely high Lp(a) (> 100 mg/dL) was associated with increased cardiovascular mortality (HR 1.5, 95% CI 1.06-2.12) compared to Lp(a) < 50 mg/dl. Both hsCRP (> 2 mg/L, HR 1.39, 95% CI 1.08-1.79 third vs. first interval) and more so IL-6 (HR 1.92, 95% CI 1.64-2.23, upper vs. lower half), were independently associated with higher CVD mortality. While hsCRP did not increase the Lp(a)-CVD mortality in stratified analysis, high IL-6 conferred an increased risk at Lp(a) levels > 100 mg/dL (HR 1.25, 95% CI 1.09-1.44).”
“Lipoprotein(a) levels were higher in women vs men and in Black vs Hispanic and White individuals. During a median follow-up of 5.4 years, 41 687 individuals (15%) experienced recurrent ASCVD. Higher lipoprotein(a) levels were associated with continuously increasing risk of recurrent ASCVD. Compared to individuals with lipoprotein(a) < 15 nmol/L, the adjusted hazard ratios for recurrent ASCVD events were 1.04 (95% confidence interval 1.01–1.07) for 15–79 nmol/L, 1.15 (1.12–1.19) for 80–179 nmol/L, 1.29 (1.25–1.33) for 180–299 nmol/L, and 1.45 (1.39–1.51) for ≥300 nmol/L. Results were similar for individual ASCVD components, and in sex, race/ethnicity, baseline ASCVD, and diabetes subgroups; however, high impact LDL cholesterol-lowering therapy possibly mitigates the deleterious effect of lipoprotein(a) ≥ 180 nmol/L, most pronounced in those on PCSK9 inhibitors. Interaction on recurrent ASCVD events between lipoprotein(a) categories and sex, race/ethnicity, baseline ASCVD, diabetes, and impact of LDL cholesterol-lowering therapy use had P-values of .61, .06, .33, .91, and 2 × 10−8, respectively.
Conclusions
In 273 770 individuals with ASCVD, higher lipoprotein(a) levels were associated with continuously increasing risk of recurrent ASCVD events regardless of sex and race/ethnicity that may have been partially mitigated by high impact LDL cholesterol-lowering therapy.“
