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Dean Pomerleau

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About Dean Pomerleau

  • Birthday 11/12/1964

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  1. Dean Pomerleau

    Sodium, Inflammation and Joint Pain

    Note - I moved discussion of Todd's high LDL to a new thread on Is High LDL-c Harmless in Otherwise Healthy People? --Dean
  2. Perfectly true. Hardcore CR should be attempted only with great care and is not recommended for people with risk factors for an eating disorder. Wow. Good luck with that. The average person in this study's [1] cohort may not have had quite as favorable markers of metabolic health (besides LDL) as you do, but they were categorized as "low risk" for CVD based on such markers (their median estimated 10-year risk of developing (let alone dying from) CVD was only 1.3%) and they didn't have nearly as high LDL as you do (median LDL-C of 205 in the highest quintile). Nevertheless those otherwise-low-CVD-risk people who were in the highest LDL quintiles died from CVD at a 50-80% higher rate during ~30 years of followup than folks with study participants with LDL less than 100. Here is the graph of CVD mortality stratified by LDL quintile: You can certainly try to argue such a study doesn't apply to you, either because of your underlying disease (KD) and/or because you are metabolically healthier than those in the upper LDL quintiles in [1]. But I would consider that a stretch and would personally be very reluctant to take the chance that very high LDL is harmless in otherwise healthy people, especially given the additional evidence from: People with familial hypercholesterolemia (who are the only population I know of whose LDL approaches yours) who have a 22x higher risk of developing heart disease than people with LDL < 130 [2]. Mendelian randomization studies (e.g. [3]) which have found that in otherwise well-matched populations, the lifetime risk of CVD in people with genetic mutations that modestly elevate their LDL is 50% higher per 38mg/dl increase in LDL. --Dean ----------- [1] Circulation. 2018 Nov 20;138(21):2315-2325. doi: 10.1161/CIRCULATIONAHA.118.034273. Long-Term Association of Low-Density Lipoprotein Cholesterol With Cardiovascular Mortality in Individuals at Low 10-Year Risk of Atherosclerotic Cardiovascular Disease. Abdullah SM(1)(2), Defina LF(3), Leonard D(3), Barlow CE(3), Radford NB(4), Willis BL(3), Rohatgi A(1), McGuire DK(1), de Lemos JA(1), Grundy SM(1)(2), Berry JD(1), Khera A(1). Author information: (1)Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas (S.M.A., A.R., D.K.M., J.A.D., S.M.G., J.D.B., A.K.). (2)Veteran's Affairs North Texas Medical Center, Dallas (S.M.A., S.M.G.). (3)The Cooper Institute, Dallas, TX (L.F.D., D.L., C.E.B., B.L.W.). (4)The Cooper Clinic, Dallas, TX (N.B.R.). BACKGROUND: The associations of low-density lipoprotein cholesterol (LDL-C) with cardiovascular disease (CVD) and coronary heart disease mortality in an exclusively low estimated 10-year risk group are not well delineated. We sought to determine the long-term associations of various LDL-C and non-high-density lipoprotein cholesterol (HDL-C) thresholds and CVD and coronary heart disease mortality in a large, low 10-year risk cohort. METHODS: The study sample included participants of the CCLS (Cooper Center Longitudinal Study) without a history of CVD or diabetes mellitus and defined as low risk (<7.5%) for 10-year atherosclerotic CVD events at baseline based on Pooled Cohort Risk Assessment Equations. The associations of fasting LDL-C and non-HDL-C with CVD mortality were tested with Cox proportional hazards models. RESULTS: In 36 375 participants (72% men, median age 42) followed for a median of 26.8 years, 1086 CVD and 598 coronary heart disease deaths occurred. Compared with LDL-C <100 mg/dL, LDL-C categories 100 to 129 mg/dL, 130 to 159 mg/dL, 160 to 189.9 mg/dL, and ≥190 mg/dL were associated with a significantly higher risk of CVD death, with hazard ratios of 1.4 (95% CI, 1.1-1.7), 1.3 (95% CI, 1.1-1.6), 1.9 (95% CI, 1.5-2.4), and 1.7 (95% CI, 1.3-2.3), and mean reductions in years free of CVD death of 1.8, 1.1, 4.3, and 3.9, respectively. After adjustment for atherosclerotic CVD risk factors, LDL-C categories 160 to 189 mg/dL and ≥190 mg/dL remained independently associated with CVD mortality, with hazard ratios of 1.7 (95% CI, 1.4-2.2) and 1.5 (95% CI, 1.2-2.1), respectively. In multivariable-adjusted models using non-HDL-C <130 mg/dL as the reference, non-HDL-C 160 to 189 mg/dL, 190 to 219 mg/dL, and ≥220 mg/dL were significantly associated with CVD death, with hazard ratios of 1.3 (95% CI, 1.1-1.6), 1.8 (95% CI, 1.4-2.2), and 1.5 (95% CI, 1.2-2.0), respectively. Restricting the cohort to those with 10-year risk <5% did not diminish the associations of LDL-C and non-HDL-C with CVD mortality. CONCLUSIONS: In a low 10-year risk cohort with long-term follow-up, LDL-C and non-HDL-C ≥160 mg/dL were independently associated with a 50% to 80% increased relative risk of CVD mortality. These findings may have implications for future cholesterol treatment paradigms. DOI: 10.1161/CIRCULATIONAHA.118.034273 PMID: 30571575 [Indexed for MEDLINE] ----------------- [2] J Am Coll Cardiol. 2016 Jun 7;67(22):2578-89. doi: 10.1016/j.jacc.2016.03.520. Epub 2016 Apr 3. Diagnostic Yield and Clinical Utility of Sequencing Familial Hypercholesterolemia Genes in Patients With Severe Hypercholesterolemia. Khera AV(1), Won HH(2), Peloso GM(3), Lawson KS(4), Bartz TM(5), Deng X(6), van Leeuwen EM(7), Natarajan P(1), Emdin CA(8), Bick AG(8), Morrison AC(4), Brody JA(9), Gupta N(8), Nomura A(10), Kessler T(11), Duga S(12), Bis JC(9), van Duijn CM(7), Cupples LA(6), Psaty B(13), Rader DJ(14), Danesh J(15), Schunkert H(11), McPherson R(16), Farrall M(17), Watkins H(17), Lander E(8), Wilson JG(18), Correa A(19), Boerwinkle E(4), Merlini PA(20), Ardissino D(21), Saleheen D(22), Gabriel S(8), Kathiresan S(23). BACKGROUND: Approximately 7% of American adults have severe hypercholesterolemia (untreated low-density lipoprotein [LDL] cholesterol ≥190 mg/dl), which may be due to familial hypercholesterolemia (FH). Lifelong LDL cholesterol elevations in FH mutation carriers may confer coronary artery disease (CAD) risk beyond that captured by a single LDL cholesterol measurement. OBJECTIVES: This study assessed the prevalence of an FH mutation among those with severe hypercholesterolemia and determined whether CAD risk varies according to mutation status beyond the observed LDL cholesterol level. METHODS: Three genes causative for FH (LDLR, APOB, and PCSK9) were sequenced in 26,025 participants from 7 case-control studies (5,540 CAD case subjects, 8,577 CAD-free control subjects) and 5 prospective cohort studies (11,908 participants). FH mutations included loss-of-function variants in LDLR, missense mutations in LDLR predicted to be damaging, and variants linked to FH in ClinVar, a clinical genetics database. RESULTS: Among 20,485 CAD-free control and prospective cohort participants, 1,386 (6.7%) had LDL cholesterol ≥190 mg/dl; of these, only 24 (1.7%) carried an FH mutation. Within any stratum of observed LDL cholesterol, risk of CAD was higher among FH mutation carriers than noncarriers. Compared with a reference group with LDL cholesterol <130 mg/dl and no mutation, participants with LDL cholesterol ≥190 mg/dl and no FH mutation had a 6-fold higher risk for CAD (odds ratio: 6.0; 95% confidence interval: 5.2 to 6.9), whereas those with both LDL cholesterol ≥190 mg/dl and an FH mutation demonstrated a 22-fold increased risk (odds ratio: 22.3; 95% confidence interval: 10.7 to 53.2). In an analysis of participants with serial lipid measurements over many years, FH mutation carriers had higher cumulative exposure to LDL cholesterol than noncarriers. CONCLUSIONS: Among participants with LDL cholesterol ≥190 mg/dl, gene sequencing identified an FH mutation in <2%. However, for any observed LDL cholesterol, FH mutation carriers had substantially increased risk for CAD. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved. DOI: 10.1016/j.jacc.2016.03.520 PMCID: PMC5405769 PMID: 27050191 [Indexed for MEDLINE] ------------- [3] Sci Rep. 2020 Jun 8;10(1):9208. doi: 10.1038/s41598-020-66027-4. In-depth Mendelian randomization analysis of causal factors for coronary artery disease. Tan YD(1), Xiao P(1), Guda C(2). Author information: (1)Department of Genetics, Cell Biology & Anatomy in Nebraska University Medical Center, Omaha, NE, 68198, USA. (2)Department of Genetics, Cell Biology & Anatomy in Nebraska University Medical Center, Omaha, NE, 68198, USA. babu.guda@unmc.edu. Selecting a set of valid genetic variants is critical for Mendelian randomization (MR) to correctly infer risk factors causing a disease. We here developed a method for selecting genetic variants as valid instrumental variables for inferring risk factors causing coronary artery disease (CAD). Using this method, we selected two sets of single-nucleotide-polymorphism (SNP) genetic variants (SNP338 and SNP363) associated with each of the three potential risk factors for CAD including low density lipoprotein cholesterol (LDL-c), high density lipoprotein cholesterol (HDL-c) and triglycerides (TG) from two independent GWAS datasets. We performed in-depth multivariate MR (MVMR) analyses and the results from both datasets consistently showed that LDL-c was strongly associated with increased risk for CAD (β = 0.396,OR = 1.486 per 1 SD (equivalent to 38 mg/dL), 95CI = (1.38, 1.59) in SNP338; and β = 0.424, OR = 1.528 per 1 SD, 95%CI = (1.42, 1.65) in SNP363); HDL-c was strongly associated with reduced risk for CAD (β = -0.315, OR = 0.729 per 1 SD (equivalent to 16 mg/dL), 95CI = (0.68, 0.78) in SNP338; and β = -0.319, OR = 0.726 per 1 SD, 95%CI = (0.66, 0.80), in SNP363). In case of TG, when using the full datasets, an increased risk for CAD (β = 0.184, OR = 1.2 per 1 SD (equivalent to 89 mg/dL), 95%CI = (1.12, 1.28) in SNPP338; and β = 0.207, OR = 1.222 per 1 SD, 95%CI = (1.10, 1.36) in SNP363) was observed, while using partial datasets that contain shared and unique SNPs showed that TG is not a risk factor for CAD. From these results, it can be inferred that TG itself is not a causal risk factor for CAD, but it's shown as a risk factor due to pleiotropic effects associated with LDL-c and HDL-c SNPs. Large-scale simulation experiments without pleiotropic effects also corroborated these results. DOI: 10.1038/s41598-020-66027-4 PMCID: PMC7280530 PMID: 32514076 [Indexed for MEDLINE]
  3. Dean Pomerleau

    Sodium, Inflammation and Joint Pain

    Todd, It is great to hear you have found a way to manage your Kennedys Disease so successfully, while others with KD of similar age are dying from its side effects. But I wonder just how generalizable and healthy your diet and lifestyle practices are long-term for people without your life threatening genetic condition. --Dean
  4. Dean Pomerleau

    Nuts and Mortality

    Interesting. It would be nice to see this n=1 experiment repeated with more subjects and with proper control (i.e. also testing PWV after eating a low-fat meal and/or a mixed meal with or without nuts). --Dean
  5. Dean Pomerleau

    Sci Fi Movie and Book Recommendations

    A time-bending, really-makes-you-think series my wife, daughter and I really enjoyed was the recent mini-series Devs. Here is the trailer: --Dean
  6. Dean Pomerleau

    Sodium, Inflammation and Joint Pain

    I sense a note of sarcasm, but I'll answer anyway. I suspect my body has adapted to a low sodium diet (perhaps by increasing the level of the salt-retaining hormone aldosterone) and as a result holds on to a lot of sodium when I do eat it, increasing my weight and blood pressure. It could be partly genetic though - since my uncle has hypertension which doesn't respond to diet or medication. As for the joint pain, I speculate I may notice swelling in the joints, particularly knees, when I'm retaining water because of the large amount of exercise I do. --Dean
  7. In my quest to add diversity to the foods I eat, I recently switched from an oatmeal-based morning porridge to making my own 10-grain hot cereal from whole grain kernals that I buy in bulk and coarse-grind myself with my vitamix. Anyway, in the first batch of this new multigrain cereal I decided to add a little salt to add some flavor. But mistakenly, I added a lot more salt than I'd intended, to the point where my daily serving of hot cereal contained about 1500mg of sodium, more than doubling my usual daily sodium intake. Being someone who hates to waste food, particularly food I worked hard to prepare myself, I decided to eat the first 2-week batch despite having much more salt than I'm used to, figuring what harm can it do. Within a day or two I noticed my weight had gone up by about 1.5 lbs, which is no big deal but nonetheless very unusual for me. But this wasn't too surprising, since I knew salt makes you retain more water to keep the salinity of your blood constant. Predictably, my blood pressure also went up by about 5-8 points. But what I wasn't expecting (but maybe should have) was that my knee joints really started aching. It wasn't quite bad enough to interfere with my unusually rigorous exercise regime, but it was close. Almost as bad as when I had Lyme disease. Now that I've been eating a salt-free batch of the multi-grain cereal for a few days, the knee pain has disappeared, along with the extra weight and higher blood pressure. Perhaps my body would have adjusted to the higher level of salt intake if I'd given it longer. There is definitely evidence that elevated dietary salt is associated with inflammation and rheumatoid arthritis [1]. Of course high sodium intake (and excretion) may be a marker for a poor quality diet overall - so it might not be the sodium that is causing the RA in [1]. But given this personal experience of increased joint pain while eating a lot of sodium, I'm not willing to continue experimenting. I recall some people around here have reported joint issues (particularly knee pain) when engaging in exercise and have been surprised at how I can exercise as much as I do and not suffer from joint pain myself. In addition to the relatively low-fat, highly anti-inflammatory vegan diet I eat, perhaps part of my good fortune in this regard results from keeping my sodium intake low. Just something to think about if you've experienced joint pain. --Dean ------------ [1] PLoS One. 2017 Oct 13;12(10):e0186157. doi: 10.1371/journal.pone.0186157. eCollection 2017. Sodium excretion is higher in patients with rheumatoid arthritis than in matched controls. Marouen S(1), du Cailar G(2), Audo R(1)(3), Lukas C(1), Vial G(4), Tournadre A(4), Barrat E(5), Ribstein J(2), Combe B(1)(3), Morel J(1)(3), Daien CI(1)(3). Author information: (1)Rheumatology Department, Lapeyronie Hospital and Montpellier University, Montpellier, France. (2)Internal medicine and hypertension, Lapeyronie Hospital and Montpellier University, Montpellier, France. (3)Institute of molecular genetic, UMR5535, CNRS, Montpellier, France. (4)Rheumatology Department, Gabriel-Montpied Hospital and Clermont-Ferrand University, Clermont-Ferrand, France. (5)Laboratoire LESCUYER, Aytré, France. OBJECTIVE: It was shown that sodium can promote auto-immunity through the activation of the Th17 pathway. We aimed to compare sodium intake in patients with rheumatoid arthritis (RA) vs. matched controls. METHODS: This case-control study included 24 patients with RA at diagnosis and 24 controls matched by age, gender and body mass index. Sodium intake was evaluated by 24-hr urinary sodium excretion. RESULTS: Sodium excretion was greater for patients with early RA (2,849±1,350 vs. 2,182±751.7mg/day, p = 0.039) than controls. This difference remained significant after adjustment for smoking and the use of anti-hypertensive and nonsteroidal anti-inflammatory drugs (p = 0.043). Patients with radiographic erosion at the time of diagnosis had a higher sodium excretion than those without (p = 0.028). CONCLUSION: Patients with early RA showed increased sodium excretion which may have contributed to autoimmunity. DOI: 10.1371/journal.pone.0186157 PMCID: PMC5640209 PMID: 29028829 [Indexed for MEDLINE] Conflict of interest statement: Competing Interests: The authors have declared that no competing interests exist. This work was supported by the Passerelle grant (Pfizer). This does not alter our adherence to PLOS ONE policies on sharing data and materials. The funder had no role in the study design, performance, data analysis or decision to publish.
  8. Dean Pomerleau

    Sci Fi Movie and Book Recommendations

    I too have enjoyed nearly all of Douglas E Richards books. I really like the Mind's Eye trilogy. Imagine my surprise when I found him quoting my research while I was at Intel on page 19 and 20 of Mind's Eye. Here is the passage: --Dean
  9. Saul, There really is no good evidence that whole grains impact inflammation one way or the other, at least in people without issues with gluten or yeast. This 2020 meta-analysis of randomized control trials [1] found if anything, whole grain consumption led to a modest reduction in markers of inflammation. --Dean --------- [1] Adv Nutr. 2020 Jan 1;11(1):52-65. doi: 10.1093/advances/nmz063. The Effect of Whole-Grain Intake on Biomarkers of Subclinical Inflammation: A Comprehensive Meta-analysis of Randomized Controlled Trials. Rahmani S(1), Sadeghi O(2)(3), Sadeghian M(4), Sadeghi N(4), Larijani B(5), Esmaillzadeh A(1)(3)(6). Findings on the effect of whole-grain consumption on inflammatory biomarkers are conflicting. This study aimed to summarize available studies on the effects of whole-grain consumption on inflammatory biomarkers in adults. Online databases including PubMed, Scopus, ISI Web of Science, and Google Scholar were searched for relevant studies published up to January 2018, using relevant keywords. We included randomized controlled trials (RCTs) investigating the effect of whole-grain foods or diets high in whole-grain foods on markers of inflammation. Studies were selected if they had a control diet low in whole grains or diets without whole grains, whether calorie restricted or not. We did not include studies that examined the effect of individual grain components, including bran or germ, or fiber-based diets. Overall, 14 RCTs, with 1238 individuals aged ≥18 y, were included. Pooling 13 effect sizes from 11 RCTs on serum C-reactive protein (CRP) concentrations, we found no significant effect of whole-grain consumption on serum CRP concentrations [weighted mean difference (WMD): -0.29 mg/L; 95% CI: -1.10, 0.52 mg/L]. However, the beneficial effects of whole-grain intake on serum CRP concentrations were observed in studies in individuals with elevated serum concentrations of CRP and studies with isocaloric diets. Combining 11 effect sizes from 10 RCTs, we found no significant effect of whole-grain consumption on serum IL-6 concentrations (WMD: -0.08 pg/mL; 95% CI: -0.27, 0.11 pg/mL). Nevertheless, we observed a significant effect of whole-grain consumption on serum IL-6 concentrations in studies in unhealthy individuals. A nonsignificant effect of whole-grain intake on circulating serum TNF-α concentrations was also seen when we summarized effect sizes from 7 RCTs (WMD: -0.06 pg/mL; 95% CI: -0.25, 0.14 pg/mL). Such a nonsignificant effect was observed for serum concentrations of plasminogen activator inhibitor-1 (PAI-1) (WMD: -3.59; 95% CI: -1.25, 8.44 kU/L). Unlike observational studies, we found no significant effect of whole-grain consumption on serum concentrations of inflammatory cytokines, including serum concentrations of CRP, IL-6, TNF-α, and PAI-1. However, beneficial effects of whole grains were found in some subgroups. Given the high between-study heterogeneity, deriving firm conclusions is difficult. Copyright © American Society for Nutrition 2019. DOI: 10.1093/advances/nmz063 PMCID: PMC7442343 PMID: 31301131 [Indexed for MEDLINE]
  10. Dean Pomerleau

    Sci Fi Movie and Book Recommendations

    What have you been smoking Gordo? 😉 My wife and I could only get through 47 minutes before giving up. I wanted to like it, but it was just too slow and predictable. [Minor spoiler below] I called it early and without seeing the ending that the "med school" student is really calling about someone she loves who is sick with cancer. We looked up the ending and are grateful we didn't bother finishing it. Palm Springs was basically the same movie except with adults and it was much sharper and funnier, IMO. --Dean
  11. Dean Pomerleau

    Sci Fi Movie and Book Recommendations

    If you are looking for a very clever, fast-paced sci-fi book with a truly novel take on time travel, Split Second by Douglas E. Richards is one of my all-time favorites: https://www.amazon.com/Split-Second-Book-ebook/dp/B014TE4FUS Best of all, its available on Kindle Unlimited for those of you with a subscription ($6.99 otherwise). --Dean
  12. Dean Pomerleau

    Sci Fi Movie and Book Recommendations

    I too enjoyed Recursion and another book by Crouch in a similar vein, Dark Matter. --Dean
  13. Dean Pomerleau

    Sci Fi Movie and Book Recommendations

    It looks a lot like "Palm Springs" with a slightly younger cast. I enjoyed Palm Springs. Have you seen it Gordo? How does it compare? --Dean
  14. Dean Pomerleau

    Sci Fi Movie and Book Recommendations

    Glad you and your family enjoyed it Gordo. I too liked the subtlety of the movie and the tongue in cheek, almost mockumentary style of it. --Dean
  15. Dean Pomerleau

    Sci Fi Movie and Book Recommendations

    No we haven't. My wife and I watched the trailer a while back and though "meh". It looks like too much of an action film for my tastes. Give "A History of Time Travel" a try. It is one movie where time travel is done well in terms of handling paradoxes etc. And it is anything but a special effects action packed movie. Plus it is only 1h:10m, not a 2.5h commitment like Tenet. --Dean
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