Women's Heart Health, Inflammation and the Gut

By Andrea McBeth, ND · Lit Review Friday, Episode 38 · Published November 2026 · 18 minute read · Sources current as of November 2026

I Think About Every Screening Except This One

Mammograms, annual exams, colonoscopies, screening labs, imaging for my arthritis. Until recently I thought very little about heart health prevention, and I am a naturopathic doctor who reads this literature for a living.

My friends and I talk about cancer, menopause and blood sugar constantly, while heart disease is the leading cause of death in women and really never on our minds.

Two women's heart health papers landed recently. Neither cites the other, and the gap between them is where this article lives. The pieces are there. Inflammation, and the microbiome's role in the system, have not been framed out yet.

Why Does The Standard Risk Calculator Miss These Women?

Because once a woman has none of the four factors it was built on, the calculator has nothing further to say about her. Preventive cardiology runs on four standard modifiable risk factors, abbreviated SMuRFs: high blood pressure, abnormal cholesterol, diabetes, and smoking. The framework is good, and the clinical shorthand for a person with none of them is “SMuRF-less.”

SMuRF-less is not the same as safe. Lifetime risk of atherosclerotic events among people without traditional risk factors reaches 21% in men and 13% in women. So Paul Ridker and colleagues asked a good question: among women with none of the four, is there anything that separates the ones who go on to have events?

What Did The Study Find?

Higher baseline inflammation predicted higher coronary risk over 30 years, linearly, with no threshold below which it stopped mattering. The analysis sits inside the Women's Health Study, a nationwide cohort of American female health professionals. Researchers measured hsCRP once, at baseline, in 12,530 women with none of the four standard risk factors, then followed them for 30 years for a first major cardiovascular event. There were 973 events.

The part the coverage left out

The three headline percentages, 77 and 39 and 52, are adjusted for age only. Add body mass index and kidney function to the model and the three endpoints stop behaving the same way.

The press release, the news coverage and the abstract all lead with the age-adjusted numbers. If you read about this study in August, you read 39% for stroke. The adjusted analysis is in Table 3.

The authors also note that in JUPITER, a randomized trial, statin therapy reduced major cardiovascular events by 38% in people who were SMuRF-less but inflamed. That is a drug trial result in a separate population, offered here as context for why identifying these women might matter clinically. It is not a recommendation, and it is not mine to make.

What Does The New Multi-Society Guidance Change?

It moves women's cardiovascular risk assessment from a snapshot to a trajectory. In the same season, the American Heart Association, in collaboration with the American College of Obstetricians and Gynecologists and endorsed by the American Academy of Pediatrics and the Society for Maternal-Fetal Medicine, published consensus guidance on female-specific cardiovascular prevention. It is a scientific statement, so it carries consensus weight and not practice-guideline weight, and it is the more important of the two documents.

Its central contribution is the Female Life Stage construct: perimenarche, ovarian cycling, perimenopause, and postmenopause, with pregnancy sitting across them as a life event when risk may emerge or be unmasked. The statement's own framing is that care for girls and women is “uniquely fragmented across clinical specialties.” Four societies agreeing to put reproductive history inside the cardiovascular record is the headline.

It also builds a door it does not walk through. It recommends considering “earlier initiation of preventive therapy or more intensive treatment even when 10-year risk is low” for a set of female-specific risk enhancers, naming endometriosis, infertility, and pregnancy loss.

“The AHA forgot inflammation” would be a cheap reading and a wrong one. A consensus statement reflects what a committee judges ready for consensus, and a cohort analysis published the same season is not that yet. The two documents are on different clocks. But a woman with an hsCRP of 4 and nothing else on her chart fits no category in either document's action framework, and she is the person this episode is about.

Where Does Low-Grade Inflammation Actually Come From?

One source, three channels, and the ground decides which one runs. That is the tryptophan fork before any of the biochemistry below.

Partly from the gut, and the clearest thread runs through a single amino acid. None of the coverage asked this. Every article treated hsCRP as a number you measure, and that version leads nowhere actionable.

Tryptophan is an essential amino acid: your own cells cannot build it, so it arrives in food. Plenty of gut bacteria can build it from scratch, which means the tryptophan supply in your gut has two sources and only one of them is your diet. Once it is there, three routes compete for the same pool. The kynurenine route is quantitatively dominant in human tissue, run by host enzymes that inflammatory signals switch on. The serotonin route runs through the gut, the body's main site of peripheral serotonin production. The microbial indole route is where gut bacteria make a family of molecules, including indole-3-propionic acid, that act on host receptors regulating barrier integrity and immune tone.

Products of all three converge on the same receptor, the aryl hydrocarbon receptor, which is why this field is harder than it looks: a molecule we file as helpful and a molecule we file as harmful can talk to the host through the same channel. Inflammatory signaling pulls tryptophan toward kynurenine. Butyrate, a fiber-fermentation product, suppresses that enzyme. A gut community's output helps set the direction, and the direction feeds back onto inflammatory tone.

Figure 1. The three aromatic amino acids, same backbone, different ring. The receptor at the centre of this story is the aryl hydrocarbon receptor, and aryl means aromatic ring. Tryptophan is the one with two fused rings, the scarcest of the three in food, and the only one gut bacteria turn into indoles.

Figure 2. One amino acid, three competing routes, one shared receptor. Butyrate from fiber fermentation suppresses the kynurenine enzyme; inflammatory signals switch it on. Deleting that enzyme from the intestinal lining in mice made plaque worse, and not through kynurenine.

Figure 3. The same fork, drawn as molecules. Only the kynurenine route breaks the ring: it leaves one ring where there were two. Serotonin and the indoles keep the ring intact and differ only in what happens to the tail, which is why blocking one branch reroutes the substrate rather than removing it.

One clarification, because our own earlier material has not always been precise about it: microbes mostly do not manufacture kynurenine themselves. They steer the host's enzyme. “Microbiota-derived kynurenine” in a paper title generally means microbiota-dependent, which is a weaker and different claim than microbial synthesis.

The result that overturned what I expected

The intuitive story is that kynurenine is the bad one and plaque follows it. A 2024 paper in Nature Communications deleted the kynurenine-pathway enzyme specifically from the cells lining the intestine in mice. Atherosclerotic plaque got worse. In the authors' words, that enzyme in those cells “protects against atherosclerosis in both males and females, in a sex- and time-dependent manner.”

The harm did not travel through kynurenine at all: fecal kynurenine levels did not correlate with plaque size. With the gut enzyme gone, tryptophan rerouted to serotonin, indole production fell, and the barrier deteriorated. Supplementing bacterial indoles relieved the plaque. Two things worth carrying: compartment matters more than concentration, since the same enzyme looks protective in the gut lining and risk-associated in blood, and blocking one branch of a branched pathway reroutes the substrate instead of removing it.

The sex-dependence showed up inside the gut. Estrogen receptor expression fell in the female small intestine and tracked inversely with the enzyme, which the authors read as sex-hormone regulation of that enzyme within the gut itself. That was in mice. Nobody has shown it in women. But it is a mechanism by which a woman's tryptophan fork could be set differently from a man's, in the tissue where the setting happens.

So I do not buy the framing where kynurenine is simply a toxin. Kynurenine made during inflammation relaxes blood vessels and lowers blood pressure in animal studies, and blocking the same enzyme in pregnant mice caused immune rejection of every genetically foreign conceptus. That is not a waste product. The common thread is dose, duration, compartment and clearance, not molecular identity. My read, and it is a read and not a finding, is that much of chronic disease is the cost of running acute-phase chemistry continuously in a body shaped for an environment that stopped existing a century ago.

Is The Gut-Heart Link Real, Or Is It The Kidney?

The marsh is full and the light is good. What has changed is the outflow. Production and clearance are different questions, and most of this section is about the second one.

Unresolved, and the resolution is not available yet. The best-studied gut-heart molecule is TMAO, and the pathway has four steps with the middle two usually skipped in retellings. Dietary choline and carnitine, from eggs, red meat and fish, are cleaved by gut bacteria into trimethylamine. The host liver oxidizes that into TMAO using an enzyme called FMO3. TMAO circulates. The kidney clears it. This is not “the red meat molecule made by bad bacteria.” It is a relay with a bacterial step, a liver step and a kidney step, and both the sex differences and the confounding live in the last two.

Women run FMO3 higher than men do, and that holds in humans and in mice both. The animal mechanism is mostly androgens suppressing it: castration raises hepatic Fmo3 messenger RNA more than a hundredfold, and dihydrotestosterone blunts that. Estrogen appears to raise it as well, but that arm is the weaker of the two, because removing the ovaries lowers FMO3 only modestly. The obvious prediction is that TMAO should predict events more strongly in women. It does not. In a case-control study of 429 matched pairs undergoing coronary angiography, TMAO predicted coronary disease only in men aged 65 and over (OR 1.57, 1.09 to 2.28). In men as a whole it was flat (OR 1.04). In women it did not separate either, and with roughly 200 women per subgroup that study could not have detected a modest effect if one were there. A clean prediction, not supported, and not refuted.

Figure 4. The four-step relay. The sex difference sits on the liver step, the clearance sits on the kidney step, and the human data says the circulating molecule does not differ by sex at all.

The broader TMAO literature does not agree with itself. Bjørnestad and colleagues examined two separate cohorts, 10,525 people in total, one of angiography patients and one community-based. After adjusting for established cardiovascular risk factors and indices of renal function, the association between circulating TMAO and 10-year death never separated from zero. Their paper is titled, flatly, that there was no association.

Which brings me back to the detail I flagged earlier. Ridker's model adjusted for kidney function in a cohort whose average kidney function was normal, and the stroke signal is the one that did not survive it. One reading is that the kidney is a nuisance variable and the adjustment is clean. Another is that kidney clearance is a participant in a gut-heart story and not noise, and that sub-threshold differences in clearance, in women the system calls healthy, are doing more than anyone has measured.

One human study pushes against the simple kidney-proxy explanation. Bogiatzi and colleagues selected patients on the mismatch between their risk factors and their actual carotid plaque, the phenomenon the Ridker paper describes measured with a different instrument. Those patients had higher TMAO and higher p-cresyl sulfate, independent of kidney function.

Does Any Of This Show Up In Large Numbers Of Actual People?

Yes, and this is the part of the literature I think gets least airtime in coverage of the Ridker paper. Two population studies, neither of them about women's hearts specifically, put gut community state and this exact inflammation marker in the same regression.

The larger one is SCAPIS, the Swedish Cardiopulmonary Bioimage Study: 8,973 people aged 50 to 65 with no known atherosclerotic disease, 53.7% of them women, each with shotgun sequencing of a stool sample and a coronary CT. Sixty-four bacterial species were associated with coronary artery calcium after adjusting for cardiovascular risk factors. Nineteen of those same species also tracked with plasma hsCRP, and sixteen with neutrophil counts. The gut-to-inflammation link and the gut-to-plaque link run through overlapping sets of organisms, in the same people, measured the same week.

Then the detail that connects it to the fork above. The species carrying most of that signal were ones that normally live in the mouth, and they were negatively associated with plasma indole-3-propionic acid, the microbial indole from the third route, and positively associated with secondary bile acids and imidazole propionate. Less of the bacterial indole product in the blood, more inflammation and more calcium in the arteries. That is the same argument the mouse paper makes, read off nine thousand people instead of a knockout strain.

The smaller one, FINRISK 2002, measured 45 cytokines plus CRP against the microbiome in 2,398 adults. A single summary measure of how diverse a person's gut community is ran inversely against CRP (about 0.06 standard deviations lower CRP per standard deviation of diversity, false-discovery-adjusted p = 0.025), along with interleukin-8 and IP-10, adjusted for age, sex, body mass index, diabetes and smoking. A small effect per person and a consistent one across a population, which is what a diffuse upstream input should look like.

Which leaves a contradiction I am going to leave standing, because I think it is the honest shape of this field right now. In the 205 sequenced patients above, selected on the mismatch between risk factors and plaque, the species list did not separate the extremes. In nine thousand unselected people, species associations with calcium and with hsCRP are all over the data. Both results can hold: a taxonomic read is close to useless for telling one person from another and still carries real signal across a population. And the molecule result in SCAPIS points the same way the small study did, because what the overrepresented species had in common was a shortage of the thing bacteria are supposed to be making.

Do Hormones And Menopause Change Any Of This?

One ground giving way to another, lit on both sides. The new guidance reorganizes prevention around life stage, which is risk read as a trajectory rather than a snapshot.

Probably, and the evidence is the thinnest part of this article. In an ELITE trial sub-study, 80 early postmenopausal women over 36 months, hormone therapy lowered kynurenic acid, a molecule one step down the same pathway, and lower levels tracked with slower thickening of the carotid artery wall. Three qualifiers change its weight: changes in tryptophan and in kynurenine itself were not associated with the artery measure, the sample was selected at the extremes, which inflates the effect size by design, and in the hormone-therapy-only subset the estradiol association did not reach significance. Hypothesis-generating, on a surrogate measure. The parent trial is more solid: hormone therapy slowed arterial progression when started in early postmenopause and not when started late.

The gap I find most frustrating is surgical menopause. Removing the ovaries is a sudden, complete, precisely dated loss of ovarian hormone production, about as close to a natural experiment as this question will get. As far as I can find, nobody has asked what it does to the tryptophan fork or to that liver enzyme. Somebody should.

So What Do I Actually Do With This?

Less than I would like, and I will say so before padding the list.

• Know the number exists. hsCRP is inexpensive and is not part of routine screening in the United States. Get a cardiolipid panel not just LDL but the sub parts, look at apo(A) and apo(B).Whether it belongs on your labs is a conversation with your own clinician, and this paper is a reasonable thing to bring to it.
• Know your family history, specifically. In this cohort, family history of heart attack was more common among the women who had events, 16.1% versus 13.1%. The thing that sits in a family and nobody mentions is the thing that shows up at sixty.
• Treat life stage as information. That is the part of the new guidance you can use immediately. Perimenopause is not a waiting room, and reproductive history is cardiovascular history.
• Notice what chronic stress is doing to your blood pressure. Mine goes up under load, and the fact that it comes back down does not mean the load was free.
• Keep the boring gut fundamentals. Fiber, fermentation substrate, a daily bowel movement. I pay a lot of attention to mine. I think it helps, and my reason is mechanistic plausibility, not an outcome trial in women like me.

The Honest Limitations

• hsCRP was measured once, at baseline, and used to predict 30 years. Inflammation is not a fixed trait, and a single measurement is a snapshot of a moving quantity.
• This is an observational cohort. It establishes that inflammation grades risk in these women. It does not establish that lowering inflammation lowers their risk. The statin trial result is suggestive and comes from a different population.
• The stroke finding does not survive adjustment. Two of three endpoints hold.
• The cohort is American female health professionals, and the paper does not report its racial composition. For a 30-year study about women who get missed by the healthcare system, missing composition data is a real limit on who the result can speak for.
• The mechanism section is mostly mice. The gut-lining enzyme result, the blood-pressure result and the pregnancy result are all animal work. They tell you what is biologically possible, not what is happening in you.
• Nothing here is medical advice, and I am not your doctor. What tests belong on your panel is a conversation with the clinician who knows your history.

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Frequently Asked Questions

What is a normal hsCRP level?

Laboratories commonly describe hsCRP below 1 mg/L as low, 1 to 3 mg/L as average, and above 3 mg/L as elevated, and in the Ridker 2026 cohort those groups split 37.7%, 32.5% and 29.8%. The finding that complicates the categories is that risk rose linearly across the entire range, with no threshold below which it stopped mattering, so no level in that study functioned as a clean all-clear.

Should I ask my doctor for an hsCRP test?

That is a decision for you and your clinician, and this article is not advice. What the research supports is that hsCRP is inexpensive, that it is not part of routine cardiovascular screening in the United States, and that in a 30-year study of women with no standard risk factors it separated the women who later had coronary events from the women who did not (Ridker et al., 2026, European Heart Journal).

Why is heart disease underdiagnosed in women?

Part of it is that the standard risk framework was not built with female physiology at the center, which is the gap the 2026 multi-society consensus statement sets out to close by organizing prevention around four female life stages and treating pregnancy as a risk-revealing event. Part of it is attention: heart disease is the leading cause of death in women, and it receives a fraction of the cultural focus that breast cancer does.

Can gut bacteria affect heart health?

Gut bacteria produce molecules that reach and act on distant organs including the cardiovascular system, and some of those molecules track with arterial disease in humans. How much of that relationship is causal is unsettled, and the main complication is that the kidney clears these molecules, so kidney function and gut output are hard to separate statistically. In one human study, gut-derived metabolites distinguished patients with unexpectedly severe carotid plaque while their gut bacterial composition did not.

Is TMAO from eggs and red meat something to worry about?

The TMAO literature does not agree with itself, so treating it as settled would be overstating it: one large two-cohort analysis found no association with 10-year mortality after adjusting for risk factors and kidney function. The food is also not the deciding factor on its own, because whether those nutrients become much TMAO depends on which bacteria are present to make the first conversion, on a liver enzyme regulated by sex hormones, and on how well the kidney clears the result.

What is the difference between probiotics and postbiotics?

Probiotics are live organisms taken with the goal that they take up residence and do work. Postbiotics are the molecular output of microbial communities, delivered without live bacteria. The reasoning behind postbiotics is that the host reads molecules, so if the organisms that make a given molecule are depleted, supplying the molecule is a plausible approach. That is a thesis, not a proven outcome.

Does perimenopause change cardiovascular risk?

The 2026 consensus statement treats the menopausal transition as a life stage when cardiovascular risk may accelerate, which is why it built life stage into the prevention framework. The biology underneath that is actively being worked out, and the research on how hormones affect gut-derived molecules specifically is thin, small, and mostly on surrogate measures.

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The Bottom Line

Twelve and a half thousand women with nothing wrong on their chart. Thirty years. Nearly a third of them walking around with an inflammation level the literature associates with meaningfully higher coronary risk, and a cheap test that would have shown it sitting unordered.

What I find most interesting is not the finding. It is that the question “where is the inflammation coming from” has barely been asked in this context, and that the most promising answers run through the gut and the kidney, which is to say through the two organs that cardiovascular risk models treat as adjustments.

I came into this one able to recite my screening history for every cancer I have been taught to fear, and knowing nothing about my own heart. I still do not know my hsCRP. I am going to find out.

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References

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2. Khan SS, Grobman WA, Angell S, et al. Consensus Guidance for the Female-Specific Prevention and Management of Cardiovascular Disease: A Scientific Statement From the American Heart Association, American Academy of Pediatrics, American College of Obstetricians and Gynecologists, and Society for Maternal-Fetal Medicine. Circulation. 2026. https://doi.org/10.1161/CIR.0000000000001482
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10. Sriprasert I, Mack WJ, Hodis HN, et al. Effect of hormone therapy on tryptophan metabolism and atherosclerosis among postmenopausal women. Climacteric. 2025. https://doi.org/10.1080/13697137.2025.2509838 · FREE FULL TEXT
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This post accompanies the Lit Review Friday episode of Learn Something with Thaena.