Stroke Prevention: What the 2024 Guideline Changes

How much of stroke is preventable?

Most of it. That is not a comforting throwaway, it is what the modeling says.

Put together a Mediterranean-style diet, regular movement, staying off cigarettes, blood pressure under control, a statin where one belongs, and an antiplatelet or anticoagulant when there is an indication for it, and the estimated cumulative reduction in recurrent vascular events comes to roughly 80%.¹ Preventing a first stroke works out about the same.

Cardiologists and neurologists organize this around the American Heart Association's Life's Essential 8: healthy diet, physical activity, weight management, healthy sleep, tobacco avoidance, and control of cholesterol, blood glucose, and blood pressure.² Which tells you what stroke prevention mostly is. It is cardiometabolic prevention, with a few stroke-specific layers over it: atrial fibrillation screening, carotid disease, PFO.

Philadelphia adds its own weight to that. Roughly one in three adults here has hypertension, and the rates run higher in Black and lower-income neighborhoods. So the arithmetic tilts toward blood pressure harder than the national averages suggest.

What does the 2024 guideline really change?

Seven things, and none of them cosmetic. The 2024 AHA/ASA Primary Prevention Guideline is the first update since 2014, so a decade of trial data arrived all at once:²³

1. Blood pressure comes down to under 130/80, a Class 1 recommendation once your ASCVD risk is elevated.
2. The Mediterranean diet picks up a Class 1 recommendation at intermediate-to-high cardiovascular risk.
3. GLP-1 receptor agonists move to Class 1A in type 2 diabetes with high cardiovascular risk or established disease.
4. Aspirin drops to Class 2b for primary prevention, and to Class 3 (harm) past age 70 without ASCVD or in chronic kidney disease.
5. Screening women for preeclampsia history, early menopause, and endometriosis becomes a Class 1 recommendation.
6. Potassium-enriched salt (75% NaCl / 25% KCl) picks up a Class 2a.
7. Colchicine gets a serious discussion as an anti-inflammatory option, mostly in people who already have coronary disease.

The rest of this is how each one shows up in your care.

Blood pressure: what's the target, and what gets you there?

Nothing else in primary prevention comes close to this. Every 10 mmHg you take off your systolic reading cuts stroke risk by about 41%.⁴

That is not a typo. It is also why blood pressure is the first thing I go after in nearly every prevention visit, sometimes to the mild irritation of people who came in to talk about their cholesterol.

The 2024 target is under 130/80 mmHg once ASCVD risk is elevated. Three trials put it there:

• SPRINT treated to a systolic under 120 and got fewer cardiovascular events than treating to 140.
• STEP ran the same question in older adults with hypertension, where aiming for under 130 instead of under 150 gave a 33% lower incident stroke risk.
• ACCORD BP looked at people with diabetes and found a 41% lower stroke risk at under 120 versus under 140, as a secondary outcome.³

In practice:

• You will probably need two or more medications. One agent rarely gets anybody to goal.
• Every major drug class lowers stroke risk apart from alpha-blockers, and ACE inhibitors and ARBs pull a little more weight for stroke than the rest.⁵
• Take the reading at home, and take it properly: seated, feet flat, arm supported, two readings a minute apart, after five minutes of sitting still. A clinic cuff, white coats around and traffic outside the window, routinely runs 5-15 mmHg high.

So if you have a smart cuff at home, here is what I ask for. Two readings, twice a day, for a week, then send me the average. A week of that tells me more than any single reading I take in the office ever will.

What does the Mediterranean diet do for stroke?

PREDIMED is the trial the rest of this rests on. It randomized 7,447 adults at high cardiovascular risk to a Mediterranean diet, supplemented with either extra-virgin olive oil or nuts, against a low-fat control. Over a median 4.8 years, the Mediterranean group had a 42% relative reduction in stroke (HR 0.58, 95% CI 0.42-0.82).⁶

How closely you follow it matters on top of that. People in the highest quintile of adherence had a 74% lower stroke risk than people in the lowest.⁷

Patients ask me what that means on a Tuesday night with 20 minutes and a tired kid in the kitchen. Here is the version I give:

• Olive oil as your main fat. PREDIMED used two to four tablespoons a day.
• A handful of nuts most days. The trial used walnuts, almonds, and hazelnuts.
• Fish at least twice a week, fatty fish where you can: salmon, sardines, mackerel.
• Beans and lentils most days.
• Vegetables and fruit at most meals.
• Whole grains in place of refined ones.
• Wine in modest amounts if you already drink. If you don't drink, this is no reason to start.
• Red and processed meat once in a while.

The low-fat arm did not reduce stroke risk meaningfully.⁶ DASH is an excellent blood pressure diet and it was never designed with stroke as an endpoint, which is why the 2024 guideline names Mediterranean by name.

Philly makes this easier than most places do. Reading Terminal, the Italian Market, the Asian markets along Washington Avenue. Cherry tomatoes, fresh basil, anchovies, and good olive oil are a normal grocery run here rather than a project.

One cheap addition. Potassium salt substitution, 75% sodium chloride and 25% potassium chloride, earned a Class 2a recommendation off the SSaSS trial, which found a 22% relative reduction in stroke in adults over 60 with elevated blood pressure.³ It costs a few dollars and hardly anybody uses it. Talk to me first if you have advanced CKD or take a potassium-sparing diuretic, an ACE inhibitor, or an ARB, because those combinations raise hyperkalemia risk.

What are the under-recognized nutritional gaps?

The Mediterranean pattern covers most of this on its own. A few gaps still slip through, and they turn up in people who, on paper, look like they are eating reasonably well.

• Magnesium is the one I chase most often. Every 100 mg/day more in the diet is associated with a 13% lower stroke risk,⁵² and Mendelian randomization supports a causal relationship for cardioembolic stroke, probably through magnesium's anti-arrhythmic effect and the lower atrial fibrillation risk that comes with it.⁵³ There is a decent way to spot depletion, the Magnesium Depletion Score, built from PPI use, diuretic use, kidney function, and alcohol intake; people in the high-depletion category carried nearly double the odds of stroke (OR 1.96).⁵⁴ It lowers blood pressure too. Pool 38 trials and you get an average drop of 2.81 mmHg systolic and 2.05 diastolic, with a much bigger effect in hypertensives already on medication (7.68 mmHg systolic) and in people with documented hypomagnesemia (5.97 systolic).⁶⁷ It improves flow-mediated dilation by roughly 3%, and in thiazide-treated hypertensive women, 600 mg/day of magnesium chelate over 6 months kept carotid intima-media thickness from progressing.⁶⁸ The average American takes in about 270 mg/day against an RDA of 320-420 mg, so most of us have room. Food comes first: pumpkin seeds, dark leafy greens, almonds, black beans, dark chocolate, fatty fish. If you supplement, use a chelated form (glycinate, taurate, threonate), which is better tolerated and better absorbed than magnesium oxide, and go carefully in advanced CKD. Keep the timing straight, though. Magnesium is no rescue therapy: IV magnesium during an acute stroke gave no functional or mortality benefit across FAST-MAG and seven other RCTs.⁶⁹ The benefit gets built over decades of eating, and no infusion at the bedside reproduces it. Forms, dosing, and interactions are in the magnesium glycinate guide.
• Potassium works independently of whatever you do with sodium. Each 1,000 mg/day increase is associated with a 9% lower stroke risk, and a combined high-magnesium, high-potassium, high-calcium dietary score put its highest quintile at a 28% lower stroke risk.⁵² Forms, food sources, and how to use a salt substitute are in the potassium guide.
• Fiber is the easiest one to fix. Every 10 g/day increase was associated with a 23% lower ischemic stroke risk across the 418,329 people in the EPIC cohort.⁵⁵ Most Americans eat about 15 g/day and the target is 25-35 g/day, which you can close in one trip to the store: beans, oats, berries, vegetables, whole grains.
• Ultra-processed food is the one I worry about here. A high UPF intake is associated with a 14% increased risk of cerebrovascular disease or death, and the effect signal ran larger in Black participants in the REGARDS cohort.⁵⁶⁵⁷ The Southern dietary pattern in that same cohort, meaning added fats, fried food, processed meats, and sugar-sweetened beverages, carried a 39% increased stroke risk.⁵⁸ Philadelphia runs on takeout, deli food, and quick-service, so trading a few of those meals a week for whole food returns more than almost anything else I can ask of you.

None of that is exotic. What I find in the office is too much sodium, too little magnesium and potassium, too little fiber, and too much ultra-processed food. The Mediterranean pattern closes most of it at once.

When does a GLP-1 receptor agonist make sense for stroke prevention?

This is the biggest addition the 2024 guideline made, and it earned the spot. If you have type 2 diabetes, an HbA1c ≥7%, and either high ASCVD risk or established cardiovascular disease, a GLP-1 receptor agonist now carries a Class 1A recommendation for primary stroke prevention.⁸

Across 28 RCTs and 74,148 patients:

• adverse cerebrovascular outcomes fell 17% (RR 0.83, 95% CI 0.76-0.91)
• ischemic stroke fell 27% (RR 0.73, 95% CI 0.60-0.89)
• the benefit held for dulaglutide and for semaglutide, injectable and oral, and ran larger when the diabetes was newer and kidney function was preserved.⁹

Head to head, GLP-1 RAs beat SGLT2 inhibitors for stroke (RR 0.77, 95% CI 0.62-0.95). SGLT2 and DPP4 inhibitors do not reduce stroke risk to a significant degree.¹⁰

SELECT hints that the benefit reaches people who are overweight or obese without diabetes, though the 2024 guideline stops short of recommending GLP-1 RAs for stroke prevention outside diabetes.¹¹ I expect that to change.

So, in practice. If you have type 2 diabetes along with established CHD, a prior stroke or TIA, peripheral arterial disease, multivessel disease on imaging, or a 10-year ASCVD risk score high enough to qualify, I stop thinking of the GLP-1 RA as a diabetes drug. It is preventive cardiology, and it belongs in the plan.

Where do fasting insulin, HOMA-IR, and the TyG index fit?

Here is where I part ways with the guideline a little.

Insulin resistance sits upstream of nearly every modifiable stroke risk factor you can name: hypertension, atherogenic dyslipidemia, atrial fibrillation risk, endothelial dysfunction, the prothrombotic state.²⁴ The 2024 guideline gets there indirectly, through diabetes management, and I think that undersells it. Catching insulin resistance years before HbA1c starts to move is one of the highest-leverage things we do in preventive care.

The observational epidemiology looks unimpressive, and the reason is instructive. A meta-analysis of seven prospective studies found no significant association between stroke and the highest versus lowest quantile of fasting insulin (pooled RR 1.18, 95% CI 0.87-1.60). A separate meta-analysis of HOMA-IR came out much the same (pooled RR 1.29).²⁵²⁶ Then look at what those analyses adjusted for. Hypertension, dyslipidemia, and inflammation all sit downstream of insulin resistance, so adjusting for them scrubs out the effect you were trying to measure.

Mendelian randomization does not have that problem. A genetic predisposition to insulin resistance, expressed as a 1-log increment in fasting insulin, carried a 33% higher risk of ischemic stroke (OR 1.33, 95% CI 1.13-1.57), and the effect ran hardest on large-artery stroke (OR 1.60) and small-vessel stroke (OR 1.63).²⁷ Genes get assigned at conception, long before lifestyle or any downstream risk factor can confound anything, which puts this about as close to causal evidence as the field gets.

What I measure:

• Fasting insulin, drawn alongside fasting glucose. I want you under 5 µIU/mL, and I start paying close attention over 10.
• HOMA-IR, which is (fasting insulin × fasting glucose) / 405. Optimal is under 1.0, insulin resistance gets defined at ≥2.5, and the IRIS trial set its entry threshold at ≥3.0.
• The TyG index, ln(fasting triglycerides × fasting glucose / 2), which comes straight off a standard lipid panel and basic metabolic panel with nothing extra to order. Across 11 cohorts covering 5.7 million subjects and 95,490 strokes, the highest TyG group carried a 27% increased stroke risk against the lowest, and the signal ran stronger for ischemic stroke (RR 1.48).²⁸
• hs-CRP, because chronic inflammation carries part of the link between insulin resistance and stroke.

When to measure:

• In primary prevention, I order fasting insulin and HOMA-IR whenever the clinical picture points that way, meaning central adiposity, acanthosis nigricans, hypertension, metabolic syndrome components, PCOS, or NAFLD, even with an HbA1c under 5.7%. In the PESA study, among people whose HbA1c was normal, a HOMA-IR ≥3 was independently associated with subclinical atherosclerosis (OR 1.74 for any coronary artery calcium above 0).³² Prediabetes amplifies the signal: in a Chinese cohort of 111,576 adults, HOMA-IR strongly predicted cardiovascular disease in prediabetes (HR 1.23) and barely predicted anything in people with normal glucose (HR 1.03).³³
• After a stroke or TIA, wait at least 14 days from the index event before you draw the fasting insulin and glucose for a HOMA-IR. Insulin sensitivity takes a temporary hit in the acute period, so an earlier draw makes you look more insulin resistant than you are.²⁹ IRIS used a threshold of ≥3.0, which is roughly the top quartile of people without diabetes.

The ARIC Study adds something useful for deciding whom to test. The link between fasting insulin and stroke ran significantly stronger in women, in whites, and in people without hypertension, each with a p-interaction below 0.05.³¹ So if your blood pressure is already well controlled, fasting insulin may be telling you more than it usually gets credit for.

Treating it pays off, and we have the trial to prove it. IRIS, the Insulin Resistance Intervention After Stroke trial, randomized 3,876 nondiabetic patients who had a recent ischemic stroke or TIA and a HOMA-IR ≥3.0 to pioglitazone, target 45 mg, or placebo. Over a median 4.8 years:²⁹

• stroke or MI fell 24% (HR 0.76, 95% CI 0.62-0.93)
• ischemic stroke on its own fell 28% (HR 0.72)
• new-onset diabetes fell 52% (HR 0.48)
• and among the prediabetes subgroup who took the drug consistently, stroke and MI fell 43%.³⁰

Pioglitazone comes with trade-offs you should hear up front: weight gain, fluid retention, higher fracture risk. Lower doses of 15-30 mg soften the side effects and probably give up some of the benefit along the way. The 2026 ADA Standards now formally endorse it for stroke or MI risk reduction after a stroke in people with insulin resistance or prediabetes, at Grade A evidence.

For primary stroke prevention, pioglitazone is not in the guideline and I don't use it there. What we have instead is lifestyle, meaning Mediterranean diet, body composition, resistance training and zone-2 cardio, sleep, and alcohol, along with metformin in some patients and GLP-1 RAs in diabetics with cardiovascular risk. Measuring fasting insulin and HOMA-IR is how we find the problem years before HbA1c moves, and those early years are when lifestyle does the most work.

What does VO₂max do for stroke risk?

If insulin resistance is the upstream metabolic lever, fitness is the upstream functional one, and it deserves the space.

Cardiorespiratory fitness (CRF) is among the strongest independent predictors of stroke risk we have. Unlike most of the others on that list, you can train it.

What the cohorts show:

• Pool 14 cohort studies and 1.4 million participants, and every 5-MET increment in CRF came with a 15% lower stroke risk (RR 0.85, 95% CI 0.79-0.91), ischemic stroke down 29% and hemorrhagic down 31%.⁴¹
• In the Kuopio Ischemic Heart Disease Study, men with a low VO₂max, under 25.2 mL/kg/min, carried a 3.2-fold higher risk of any stroke than fit men above 35.3 mL/kg/min, which puts fitness in the same predictive company as systolic blood pressure, smoking, and LDL.⁴²
• The Henry Ford FIT Project followed 67,550 patients. Reaching ≥12 METs came with a 58% lower stroke risk than the least-fit group, and each 1-MET improvement between serial exercise tests was independently associated with a 9% lower ischemic stroke risk (HR 0.91, 95% CI 0.88-0.94). Where you are heading counts as much as where you started.⁴³
• Over 7 years in a Norwegian cohort, men who improved their fitness had a 60% lower stroke risk (HR 0.40), and men who lost fitness had a 2.35-fold higher risk.⁴⁴
• The Cooper Center Longitudinal Study, 19,815 people, put midlife CRF in the top two quintiles at a 37-39% lower stroke risk after age 65, and that association survived adjustment for incident hypertension, diabetes, and atrial fibrillation. Midlife fitness is protecting you through pathways the traditional risk factors miss.⁷⁰

The AHA has argued we should measure CRF routinely, the way we already track blood pressure and BMI.⁴⁵ It outperforms both the Framingham Risk Score and the ACC/AHA Pooled Cohort Equations for predicting cardiovascular and all-cause mortality, improving net reclassification by 12-13% when you add it to the standard scores. I want it on your dashboard next to your lipids.

Two things about the dose-response curve that most people underweight:

1. The largest single gain comes from getting off the couch at all. A meta-analysis of 752,050 participants found that even below-target leisure-time activity reduced stroke risk by 18%, and hitting the ideal target reduced it by 29%.⁴⁶ A 2026 network meta-analysis of 50 RCTs found structured exercise on its own reduced stroke incidence by 60%.⁴⁷
2. For stroke, the curve flattens. In the Aerobics Center Longitudinal Study, the fittest men (13.1 METs) had a 68% lower stroke-death risk than the least fit (8.5 METs), but moderate fitness (10.5 METs) already delivered 63% of that benefit. You do not have to be elite to protect your brain, you have to clear the moderate-fitness threshold. All-cause mortality behaves differently, with no upper threshold of harm, and benefit still accruing at 14+ METs.⁷¹

The 2024 AHA/ASA target is 150 minutes a week of moderate-intensity aerobic activity, or 75 minutes a week of vigorous activity, plus strength training at least two days a week. Sitting counts against you separately: every hour beyond about 6.5 hours a day of sedentary time raises stroke risk by roughly 6%, whatever you did at the gym that morning.⁸

Here is what that looks like in Philadelphia.

If you are starting from sedentary, please do not skip the ramp-up. The 150-minute target is a steady state you build toward over weeks, and going too hard in week one is the most common reason people quit by week three. The best evidence on re-conditioning somebody starting from zero comes out of cardiac and stroke rehab, where investigators had to work out how to get profoundly deconditioned patients moving without triggering an event. Those principles transfer to a healthy 35- or 45-year-old who has been sedentary for five years. The framework is multiple shorter bouts, 5-15 minutes spread through the day, which produce a training effect at intensities as low as 30-40% of heart-rate reserve in unfit adults. A reasonable 8-12 week ramp starts with two 10-15 minute walks a day at RPE 11-12 (Borg, "feels like light exercise"), adds one slightly harder session each week, and reaches the steady-state target around month three. What predicts stroke is the trajectory, so the whole goal is to get on that curve.

• Zone 2 cardio 3-4 days a week, 30-45 minutes at a time: a brisk walk on Forbidden Drive, a steady bike ride along the Schuylkill River Trail, an easy jog around Boathouse Row. Zone 2 is the heart-rate band where you can still hold a conversation but it is mildly inconvenient, roughly 60-70% of your max heart rate.
• One zone-5 session a week, meaning a higher-intensity interval workout. 4 minutes hard and 3 minutes easy, repeated 4 times, is the Norwegian protocol, and it works for most people. This is the session that moves VO₂max.
• Two strength sessions a week covering the major movement patterns: squat, hinge, press, pull, carry.
• Daily walking to keep sedentary hours under 6-7. The easiest version is a 10-minute walk after each meal, which also blunts the glucose rise that follows it.

If you take one habit out of this section, make it this: measure your CRF and track it. A formal CPET in a lab gives you a true VO₂max, a treadmill-derived MET estimate at a stress test is a reasonable surrogate, and a Garmin or Apple Watch estimate is imperfect but useful for the trend. Where the line is heading predicts stroke better than where it sits today.

One technical note if you're on a beta-blocker, which plenty of people are for blood pressure, AF, or migraine prevention. Heart-rate-based training zones stop being reliable, because the beta-blocker blunts the relationship between heart rate and workload. Percentage-of-VO₂peak prescriptions misclassify intensity in 67-74% of patients on beta-blockers. So we anchor intensity to perceived exertion, Borg 11-12 for zone 2 and 15-17 for hard intervals, or to the talk test, where conversational is zone 2 and gasping is hard. If a formal CPET is available, we set your targets at the ventilatory threshold, which does not care about your heart rate at all.

What's the right approach to lipids for stroke prevention?

Statins cut the risk of a first stroke by about 19-22% in adults at high cardiovascular risk.⁴ Atorvastatin and rosuvastatin are the most potent of them for event reduction.

The 2026 ACC/AHA Dyslipidemia Guideline sets the escalation: statin first, then ezetimibe, then a PCSK9 inhibitor when LDL-C targets stay out of range in high-risk primary prevention.¹²

• Add a PCSK9 inhibitor to a statin and stroke odds fall 23% (OR 0.77, 95% CI 0.67-0.89) across 20 RCTs, though nobody has tested one in pure primary stroke prevention yet.⁴
• Bempedoic acid trended favorably for stroke in CLEAR Outcomes without reaching significance (HR 0.76, 95% CI 0.46-1.26).²
• High-intensity statin therapy, atorvastatin 80 mg or equivalent, is the standard after a non-embolic ischemic stroke with an LDL over 100, and established atherosclerosis gets a target under 70 mg/dL.¹³

One more lever, and most people have never been offered it: Lp(a) testing. About one in five adults carries an elevated Lp(a), which raises stroke risk on its own and runs in families. We test it once, and the number tells us how assertive to be with everything else that is modifiable. Full write-up here: Lp(a): The Genetic Heart Risk.

What about aspirin?

This is probably the most consequential change in the 2024 guideline, and the one that surprises people most. Aspirin for primary prevention came down:

• Class 2b, uncertain benefit, in people with no prior cardiovascular disease.
• Class 3, harm, in adults aged 70 and older without established ASCVD.
• Class 3, harm, in patients with chronic kidney disease and no ASCVD.³

If you have been taking a daily 81 mg "for your heart" without a clear cardiovascular indication, bring it up with me. The bleeding risk, intracranial bleeding in particular, was underweighted in the older guidelines.

ASCEND settled the modern view: 15,480 people with diabetes and no prior cardiovascular disease. Aspirin cut serious vascular events by a relative 12%, 8.5% against 9.6%, and raised major bleeding by a relative 29%, 4.1% against 3.2%, most of it gastrointestinal. Benefit and harm came out roughly even.³⁴ The estimated number needed to treat to prevent one vascular event in a modern population runs around 1,745, so any meaningful bleeding risk tips the whole calculation.

ASCEND is also the kind of trial that makes this work easier to do well. It enrolled the exact people I get asked about, high-risk diabetics who have never had a cardiovascular event, and it reported absolute event rates and absolute bleeding rates, which translate straight to the person sitting across from me with no extrapolation. The work from there is matching that population answer to your bleeding history, your age, your kidney function, and everything else competing for your attention. That is where a long relationship pays off. The trial gives the starting point, and your physician fits it to you over time.

A practical filter. Aspirin is essentially contraindicated for primary prevention if any of these apply: age ≥70 without ASCVD, chronic kidney disease without ASCVD, prior peptic ulcer disease or GI bleed, concurrent anticoagulation, active or recent intracranial bleeding, thrombocytopenia, or a chronic NSAID requirement that cannot be deprescribed. The 2019 ACC/AHA Primary Prevention Guideline gives a Class III (Harm) recommendation for primary prevention aspirin in every one of those groups.³⁵

There is a newer wrinkle. Ticagrelor 60 mg added to aspirin beyond 12 months, out to 3 years, is a Class 2b option for stroke prevention in stable coronary heart disease with low bleeding risk, on the strength of PEGASUS-TIMI 54 and its 15% relative stroke reduction.³

Secondary prevention is a different story, and antiplatelet therapy stays. Short-term dual antiplatelet therapy with aspirin and clopidogrel for 21-90 days is recommended after a minor stroke or high-risk TIA that presents within 24 hours. Long-term dual therapy is not, because of bleeding.¹⁴

Atrial fibrillation: the biggest single-intervention win

Anticoagulation for atrial fibrillation gives the largest single-intervention risk reduction we have for stroke, roughly 64% (95% CI 49-74%).⁴ No other single decision in this article does that much.

The practical playbook:

• Screen for AF in adults at risk, particularly after 65 or while working up a cryptogenic stroke. Apple Watches and other wearables have made opportunistic screening much easier, and an abnormal rhythm notification is a good reason to come in and confirm it.
• Use a DOAC rather than warfarin for non-valvular AF. You get a 19% reduction in stroke or systemic embolism and a 51% reduction in hemorrhagic stroke.¹⁵
• Apixaban is the one I pick for anybody with a history of GI bleeding. Population cohorts show significantly less GI bleeding than rivaroxaban (HR 0.33-0.54) or dabigatran (HR 0.39-0.46), and it was the only DOAC that did not significantly increase GI bleeding against warfarin in its pivotal trial.³⁶
• The threshold is generally an annual stroke risk of ≥2%, which works out to CHA₂DS₂-VASc ≥2 in men and ≥3 in women.²¹⁶
• Aspirin is not adequate here, and it should not substitute for anticoagulation.¹⁷
• Left atrial appendage occlusion (LAAO) is there for high-bleeding-risk AF patients who have relative or absolute contraindications to long-term anticoagulation, per the 2023 ACC/AHA/ACCP/HRS guideline.³⁷
• After a cryptogenic stroke, keep monitoring. A loop recorder or extended Holter is recommended when no other cause turns up.¹⁴

What's new for women?

The 2024 guideline introduced Class 1 recommendations for screening women for sex-specific stroke risk enhancers, which is a meaningful departure from 2014.¹⁸¹⁹ The list is short, and most women I meet have never been asked about any of it:

• Hypertensive disorders of pregnancy, meaning preeclampsia, eclampsia, or gestational hypertension, carry an 80% increased lifetime risk of ischemic stroke (RR 1.80, 95% CI 1.49-2.18).²⁰
• Premature ovarian failure before 40 and early-onset menopause before 45 both raise stroke risk.
• Endometriosis is newly recognized as a stroke risk enhancer.
• Preterm delivery and stillbirth carry 62% and 86% increased stroke risk respectively.²⁰
• Combined hormonal contraceptives are an independent risk factor, particularly in women aged 30-49.²¹
• Late menopause at 55 or later comes with increased hemorrhagic stroke risk.

Midlife, roughly 40 to 65, is the key window for stroke and dementia prevention in women. Hormonal, metabolic, and vascular changes converge in that stretch, and what happens during it carries unusual weight.¹⁹

So if you had preeclampsia 20 years ago and nobody has revisited your cardiovascular screening since, let's fix that. It comes up more often than it should.

Should I be checking my carotids?

For most people, no. The USPSTF does not recommend routine screening of asymptomatic adults for carotid stenosis, because intervening on an incidental moderate stenosis tends to cause more harm than it prevents. Two exceptions:

• Severe symptomatic ipsilateral stenosis after an ischemic stroke or TIA, where carotid endarterectomy or stenting is indicated relatively early after the event.¹⁴
• Multivessel atherosclerosis found on imaging done for some other reason, which often does trigger carotid imaging.

What I do look at, when you are interested and the risk profile supports it, is a coronary calcium score (CAC), or Cleerly AI plaque analysis in higher-risk patients. Plaque in the coronaries is a good proxy for vascular age everywhere else, and it changes the calculus on statin intensity, blood pressure targets, and aspirin.

What about secondary prevention after a stroke or TIA?

After an ischemic event, the 2021 AHA/ASA Secondary Prevention Guideline personalizes strategy to the stroke subtype.¹⁴ The high-level moves:

• Get blood pressure under 130/80, which reduces recurrent stroke risk by about 20% compared with looser targets.²² Thiazides, ACE inhibitors, and ARBs are the preferred agents.
• Start a high-intensity statin for non-embolic stroke with an LDL over 100, escalating with ezetimibe or a PCSK9 inhibitor until the LDL is under 70 mg/dL.¹³
• Hold HbA1c at 7% or below, with metformin plus either a GLP-1 RA or an SGLT2 inhibitor.¹³
• Use a DOAC for non-valvular AF, and keep monitoring for occult AF when no other cause is identified.
• Consider pioglitazone in nondiabetic patients with a HOMA-IR ≥3.0 or prediabetes, on the strength of IRIS and its 24% reduction in stroke or MI. Weigh it against weight gain and fracture risk.
• PFO closure is reasonable in patients aged 18-60 with a nonlacunar stroke, no other identified cause, and high-risk PFO features.¹⁴
• Do not empirically anticoagulate an embolic stroke of undetermined source (ESUS). NAVIGATE-ESUS and RE-SPECT ESUS both found no benefit of rivaroxaban or dabigatran over aspirin.¹⁴
• Lifestyle carries as much weight here as anywhere: Mediterranean diet, sodium reduction, moderate physical activity, quitting smoking, weight management.

What about supplements?

Short section, because the evidence is mostly negative and one popular supplement looks like it increases stroke risk.

What may help:

• Folic acid is the one supplement with convincing RCT evidence for stroke prevention. Pool 7 RCTs and 24,525 participants and you get a 21% relative reduction in stroke risk (RR 0.79; NNT 148).⁴⁸ The catch is where that signal comes from: mostly the CSPPT trial in China, where wheat flour is not folate-fortified. US flour has been fortified since 1998, so extra folic acid does much less here. Where it earns its place: elevated homocysteine, MTHFR polymorphisms, documented folate deficiency. Hyperhomocysteinemia shows up in roughly 19% of stroke patients, and 10-19% of stroke and TIA patients have metabolic B12 deficiency on careful testing, which is a missed opportunity that does not need to wait for a stroke to surface.⁷³ How we test for it, homocysteine, MMA, and MCV rather than serum B12 and folate, with treat-to-target thresholds of tHcy below 7 and MCV below 86, is in the B-complex guide.
• B-complex vitamins, folate plus B6 plus B12, reduced stroke risk by about 10% (RR 0.90) in a pooled analysis, again with most of the signal in populations whose flour is not fortified.⁴⁸
• Icosapent ethyl (Vascepa), a prescription rather than a supplement, reduced stroke by 28% in REDUCE-IT (HR 0.72), but only in patients who already had cardiovascular disease or diabetes, were already on a statin, and still had high triglycerides.⁴⁹ That is a different thing from over-the-counter fish oil.

What does not help, despite the marketing:

• Vitamin D on its own showed no reduction in CVD events or stroke in VITAL, the largest randomized trial of vitamin D for cardiovascular prevention, with 25,871 adults on 2,000 IU/day or placebo (HR 0.97), and that held even in participants who started with a 25(OH)D under 20 ng/mL.⁵⁰ UK Biobank data do show severe deficiency, under 25 nmol/L, tracking with a 40% higher stroke risk, but Mendelian randomization does not support a causal link for stroke, unlike dementia, where causality is confirmed.⁵⁹ So test it, treat documented deficiency in a targeted way, and don't supplement reflexively for stroke risk reduction alone. The vitamin D3 guide has the full clinical workup.
• Marine omega-3 at 1 g/day showed no stroke benefit in that same VITAL cohort.⁵⁰ The omega-3 story has more to it, and it gets its own section below.
• Multivitamins, vitamin C, vitamin E, selenium, and antioxidant combinations showed no stroke benefit in RCTs, and antioxidant mixtures showed a marginally increased stroke risk.
• Niacin showed no stroke benefit, and a marginally significant increase in all-cause mortality when added to a statin.

What appears to cause harm:

• Calcium supplements, with or without vitamin D, were associated with an increased stroke risk (RR 1.17, 95% CI 1.06-1.30) across 7 RCTs.⁵¹ The mechanism is plausible: supplemental calcium produces rapid rises in serum calcium that dietary calcium does not, and that appears to accelerate vascular calcification. I have seen ischemic strokes in patients as young as their early 50s who were taking long-term calcium with no clear indication for it.

So here is the clinical version. Dietary calcium is fine and important; supplemental calcium without a documented deficiency or an osteoporosis indication is a different matter. For most adults, 1,000-1,200 mg/day from food, meaning dairy, leafy greens, fortified plant milks, sardines, and tofu, is the right approach. If you do need to supplement, split the doses to 500 mg or less at a time and pair them with vitamin D and weight-bearing exercise. We revisit this at every membership review, particularly with postmenopausal women who were started on calcium by a previous clinician. The full picture is in the calcium guide.

What about the Omega-3 Index?

Omega-3 is my favorite example of why biomarker-guided prevention beats blanket supplementation. The Omega-3 Index (O3I) is the percentage of EPA and DHA in your red blood cell membranes, and it tracks long-term tissue omega-3 status better than any single plasma measurement.⁶⁰ The risk zones:

• High risk: an O3I under 4%
• Intermediate: 4-8%
• Guideline-acknowledged "low risk" floor: above 8%
• Our target: 12-15% (this matches the tissue saturation seen in populations with the lowest cardiovascular and dementia event rates, and it is set above the conventional Harris/von Schacky floor)

An O3I above 8% has been associated with roughly a 90% lower risk of sudden cardiac death than an O3I under 4%, and each 1-SD increase with a 15% lower CHD mortality (HR 0.85).⁶¹ In the Framingham Offspring cohort, the highest O3I quintile, above 6.8%, had 39% lower incident CVD and 34% lower all-cause mortality over 7.3 years.⁶² A 2024 analysis found that adding the O3I to the Pooled Cohort Equations meaningfully improved 10-year ASCVD risk prediction.⁶³

For stroke specifically, the observational signal is there but smaller than it is for coronary disease. Pooling 29 prospective cohorts, 183,291 participants and 10,561 strokes, the highest quintile of EPA carried 17% lower total stroke (HR 0.83) and 18% lower ischemic stroke (HR 0.82) than the lowest.⁶⁴

Then comes the catch. RCT supplementation data are mostly neutral for stroke: a Cochrane review of 31 trials found omega-3 supplementation made little or no difference (RR 1.02).⁶⁵ There is one exception. EPA monotherapy, icosapent ethyl in REDUCE-IT, reduced non-fatal stroke by 29% (RR 0.71), while combination EPA+DHA products did not.⁴⁹ And high-dose omega-3 above 1 g/day increases atrial fibrillation risk (HR ~1.49), which could raise cardioembolic stroke risk on its own.⁶⁶

So the practical version:

• Fatty fish first. Two to three servings a week of salmon, sardines, mackerel, anchovies, or trout will move your O3I more reliably than most over-the-counter capsules.
• Test the O3I if your cardiovascular risk is elevated and the answer would change something. Quest, Labcorp, and several direct-to-consumer panels all run it.
• If your O3I stays below target despite the dietary work, treat the gap. High-EPA formulations get closer to the REDUCE-IT signal than mixed EPA+DHA tonics do, and doses above 1 g/day need an explicit conversation about AF risk, particularly in older adults or anybody with palpitations.
• An OTC fish oil bottle on the counter, dose unknown and brand unverified, is the version that produced the negative RCT results. We can do better than that.

One note on the guideline tension here. The 2024 AHA/ASA Primary Prevention of Stroke Guideline gave omega-3 supplementation a Class 3 (no benefit) recommendation, based on the body of trials that used about 1 g/day of mixed EPA+DHA with no biomarker targeting. My read is that the null result reflects product quality, dose, and protocol rather than a failure of omega-3 itself. When we prescribe omega-3 for ASCVD and cerebrovascular risk reduction, we use Lovaza (Rx EPA+DHA) when insurance covers it, icosapent ethyl (Vascepa) at 4 g/day when you meet REDUCE-IT criteria, or specific well-vetted third-party-tested EPA+DHA formulations at 2-3 g/day, dosed to an O3I target. The omega-3 guide walks through that decision in full.

How we work this in primary care

Stroke prevention is not a visit or a number. It is an accumulation of small decisions, made consistently, over decades. Inside our membership that looks like this:

• The baseline visit maps your modifiable risk factors: home BP averages, ApoB, Lp(a), HbA1c, fasting insulin, a fasting lipid panel, kidney function, body composition, sleep quality, alcohol, and, for women, reproductive history.
• A CAC score where it fits, or Cleerly plaque imaging if your risk is higher.
• A medication review that asks the blunt questions. Are you on aspirin you should not be on. Are you missing a GLP-1 RA you should be on. Is your statin at the right intensity. Is your blood pressure regimen getting you to under 130/80.
• For women, an explicit reproductive and menopausal history with the 2024 risk enhancers in mind.
• For anybody over 65 or with palpitations, opportunistic AF screening with a wearable or an office EKG.

This is where a long primary care relationship earns its keep. The 2024 guideline is a long list of tools, and each one carries a benefit profile and a side-effect profile that depend on who is in the room. Pioglitazone helps when your HOMA-IR is high, and the fracture risk changes the math if you also have osteoporosis. A GLP-1 RA is Class 1A in diabetes with cardiovascular risk, and a history of pancreatitis or medullary thyroid cancer changes the choice. Aspirin can save a life in established disease and end one in somebody with a prior GI bleed. Pulling the benefit out of each tool while managing its risk is the work of fitting a guideline to a person instead of a person to a guideline. It takes time, and it takes knowing you. That is what the membership is built around.

Scientific References

1. Bridgwood B, Lager KE, Mistri AK, et al. Interventions for improving modifiable risk factor control in the secondary prevention of stroke. Cochrane Database Syst Rev. 2018.

2. Bushnell C, Kernan WN, Sharrief AZ, et al. 2024 Guideline for the Primary Prevention of Stroke: A Guideline From the American Heart Association/American Stroke Association. Stroke. 2024.

3. Razavi AC, Troy AL, Patel J, et al. Future of Stroke Prevention: 7 Updates in the 2024 AHA/ASA Primary Prevention of Stroke Guideline. JACC Adv. 2025.

4. Diener HC, Hankey GJ. Primary and Secondary Prevention of Ischemic Stroke and Cerebral Hemorrhage: JACC Focus Seminar. J Am Coll Cardiol. 2020.

5. Hilkens NA, Casolla B, Leung TW, de Leeuw FE. Stroke. Lancet. 2024.

6. Estruch R, Ros E, Salas-Salvadó J, et al. Primary Prevention of Cardiovascular Disease with a Mediterranean Diet Supplemented with Extra-Virgin Olive Oil or Nuts. N Engl J Med. 2018.

7. Castro-Barquero S, Rimm EB, Jovin TG, et al. Adherence to Different Dietary Patterns and Subsequent Risk of Total, Ischemic, and Hemorrhagic Stroke. Stroke. 2026.

8. Wilson LM, Anderson TS. Use and Eligibility for GLP-1 Receptor Agonist Treatment for Primary Prevention of Stroke. Neurology. 2025.

9. Banerjee M, Pal R, Mukhopadhyay S, Nair K. GLP-1 Receptor Agonists and Risk of Adverse Cerebrovascular Outcomes in Type 2 Diabetes: A Systematic Review and Meta-Analysis of RCTs. J Clin Endocrinol Metab. 2023.

10. Drake T, Landsteiner A, Langsetmo L, et al. Newer Pharmacologic Treatments in Adults With Type 2 Diabetes: A Systematic Review and Network Meta-Analysis for the American College of Physicians. Ann Intern Med. 2024.

11. Hosseinpour A, Sood A, Kamalpour J, et al. GLP-1 Receptor Agonists and Major Adverse Cardiovascular Events in Patients With and Without Diabetes: A Meta-Analysis of RCTs. Clin Cardiol. 2024.

12. Blumenthal RS, Morris PB, Gaudino M, et al. 2026 ACC/AHA Guideline on the Management of Dyslipidemia. J Am Coll Cardiol. 2026.

13. Ford B, Peela S, Roberts C. Secondary Prevention of Ischemic Stroke: Updated Guidelines From AHA/ASA. Am Fam Physician. 2022.

14. Kleindorfer DO, Towfighi A, Chaturvedi S, et al. 2021 Guideline for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack: A Guideline From the American Heart Association/American Stroke Association. Stroke. 2021.

15. Greco A, Occhipinti G, Giacoppo D, et al. Antithrombotic Therapy for Primary and Secondary Prevention of Ischemic Stroke: JACC State-of-the-Art Review. J Am Coll Cardiol. 2023.

16. Ko D, Chung MK, Evans PT, Benjamin EJ, Helm RH. Atrial Fibrillation: A Review. JAMA. 2025.

17. Michaud GF, Stevenson WG. Atrial Fibrillation. N Engl J Med. 2021.

18. David PS, Nordhues H, Vegunta S. Sex-Specific Risk Factors for Stroke in Women: Focus on the 2024 AHA/ASA Guideline. Cleve Clin J Med. 2026.

19. Pikula A, Iziduh S, Kocabas E, et al. Midlife as the Critical Window for Women's Stroke and Dementia Prevention. Stroke. 2026.

20. Poorthuis MH, Algra AM, Algra A, Kappelle LJ, Klijn CJ. Female- and Male-Specific Risk Factors for Stroke: A Systematic Review and Meta-Analysis. JAMA Neurol. 2017.

21. van Os HJA, Kanning JP, Ferrari MD, et al. Added Predictive Value of Female-Specific Factors and Psychosocial Factors for the Risk of Stroke in Women Under 50. Neurology. 2023.

22. Kernan WN, Viera AJ, Billinger SA, et al. Primary Care of Adult Patients After Stroke: A Scientific Statement From the AHA/ASA. Stroke. 2021.

23. Ebrahimi F, Ebrahimi R, Beer M, et al. Colchicine for the Secondary Prevention of Cardiovascular Events. Cochrane Database Syst Rev. 2025.

24. Ding PF, Zhang HS, Wang J, et al. Insulin Resistance in Ischemic Stroke: Mechanisms and Therapeutic Approaches. Front Endocrinol. 2023.

25. Xun P, Wu Y, He Q, He K. Fasting Insulin Concentrations and Incidence of Hypertension, Stroke, and Coronary Heart Disease: A Meta-Analysis of Prospective Cohort Studies. Am J Clin Nutr. 2013.

26. Gu T, Yang Q, Ying G, Jin B. Lack of Association Between Insulin Resistance as Estimated by Homeostasis Model Assessment and Stroke Risk: A Systematic Review and Meta-Analysis. Med Hypotheses. 2020.

27. Georgakis MK, Harshfield EL, Malik R, et al. Diabetes Mellitus, Glycemic Traits, and Cerebrovascular Disease: A Mendelian Randomization Study. Neurology. 2021.

28. Feng X, Yao Y, Wu L, et al. Triglyceride-Glucose Index and the Risk of Stroke: A Systematic Review and Dose-Response Meta-Analysis. Horm Metab Res. 2022.

29. Kernan WN, Viscoli CM, Furie KL, et al. Pioglitazone after Ischemic Stroke or Transient Ischemic Attack (IRIS). N Engl J Med. 2016.

30. Spence JD, Viscoli CM, Inzucchi SE, et al. Pioglitazone Therapy in Patients With Stroke and Prediabetes: A Post Hoc Analysis of the IRIS Randomized Clinical Trial. JAMA Neurol. 2019.

31. Rasmussen-Torvik LJ, Yatsuya H, Selvin E, Alonso A, Folsom AR. Demographic and Cardiovascular Risk Factors Modify Association of Fasting Insulin With Incident Coronary Heart Disease and Ischemic Stroke (Atherosclerosis Risk in Communities Study). Am J Cardiol. 2010.

32. Iglesies-Grau J, Garcia-Alvarez A, Oliva B, et al. Early Insulin Resistance in Normoglycemic Low-Risk Individuals Is Associated With Subclinical Atherosclerosis. Cardiovasc Diabetol. 2023.

33. Wang T, Li M, Zeng T, et al. Association Between Insulin Resistance and Cardiovascular Disease Risk Varies According to Glucose Tolerance Status: A Nationwide Prospective Cohort Study. Diabetes Care. 2022.

34. ASCEND Study Collaborative Group, Bowman L, Mafham M, et al. Effects of Aspirin for Primary Prevention in Persons with Diabetes Mellitus. N Engl J Med. 2018.

35. Arnett DK, Blumenthal RS, Albert MA, et al. 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease. J Am Coll Cardiol. 2019.

36. Lip GYH, Benamouzig R, Martin AC, et al. Comparative Safety and Effectiveness of Oral Anticoagulants in Patients With Non-Valvular Atrial Fibrillation and High Risk of Gastrointestinal Bleeding: A Nationwide French Cohort Study. PLoS One. 2024.

37. Doshi SK, Kar S, Nair DG, et al. Left Atrial Appendage Closure or Anticoagulation for Atrial Fibrillation (CHAMPION-AF). N Engl J Med. 2026.

38. Ramadan A, Doma M, Ferreira Felix I, et al. Recurrent Gastrointestinal Bleeding in Patients With Atrial Fibrillation Treated With Left Atrial Appendage Occlusion. Pacing Clin Electrophysiol. 2026.

39. Newman CB, Preiss D, Tobert JA, et al. Statin Safety and Associated Adverse Events: A Scientific Statement From the American Heart Association. Arterioscler Thromb Vasc Biol. 2019.

40. Lloyd-Jones DM, Morris PB, Ballantyne CM, et al. 2022 ACC Expert Consensus Decision Pathway on the Role of Nonstatin Therapies for LDL-Cholesterol Lowering. J Am Coll Cardiol. 2022.

41. Wang Y, Li F, Cheng Y, Gu L, Xie Z. Cardiorespiratory Fitness as a Quantitative Predictor of the Risk of Stroke: A Dose-Response Meta-Analysis. J Neurol. 2020.

42. Kurl S, Laukkanen JA, Rauramaa R, et al. Cardiorespiratory Fitness and the Risk for Stroke in Men. Arch Intern Med. 2003.

43. Ehrman JK, Keteyian SJ, Johansen MC, et al. Improved Cardiorespiratory Fitness Is Associated With Lower Incident Ischemic Stroke Risk: Henry Ford FIT Project. J Stroke Cerebrovasc Dis. 2023.

44. Prestgaard E, Mariampillai J, Engeseth K, et al. Change in Cardiorespiratory Fitness and Risk of Stroke and Death: Long-Term Follow-Up of Healthy Middle-Aged Men. Stroke. 2019.

45. Ross R, Blair SN, Arena R, et al. Importance of Assessing Cardiorespiratory Fitness in Clinical Practice: A Case for Fitness as a Clinical Vital Sign: A Scientific Statement From the American Heart Association. Circulation. 2016.

46. De Santis F, Romoli M, Foschi M, et al. Risk of Stroke With Different Levels of Leisure-Time Physical Activity: A Systematic Review and Meta-Analysis of Prospective Cohort Studies. J Neurol Neurosurg Psychiatry. 2024.

47. Nguyen NQ, Ta KT, Chuang KJ. Comparative Effects of Non-Pharmacological Interventions for Stroke Prevention in Adults: A Network Meta-Analysis. Cerebrovasc Dis. 2026.

48. Jenkins DJA, Spence JD, Giovannucci EL, et al. Supplemental Vitamins and Minerals for Cardiovascular Disease Prevention and Treatment: JACC Focus Seminar. J Am Coll Cardiol. 2021.

49. Bhatt DL, Steg PG, Miller M, et al. Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia (REDUCE-IT). N Engl J Med. 2019.

50. Manson JE, Bassuk SS, Cook NR, et al. Vitamin D, Marine n-3 Fatty Acids, and Primary Prevention of Cardiovascular Disease: Current Evidence (VITAL). Circ Res. 2020.

51. Michos ED, Cainzos-Achirica M, Heravi AS, Appel LJ. Vitamin D, Calcium Supplements, and Implications for Cardiovascular Health: JACC Focus Seminar. J Am Coll Cardiol. 2021.

52. Adebamowo SN, Spiegelman D, Willett WC, Rexrode KM. Association Between Intakes of Magnesium, Potassium, and Calcium and Risk of Stroke: 2 Cohorts of US Women and Updated Meta-Analyses. Am J Clin Nutr. 2015.

53. Larsson SC, Traylor M, Burgess S, et al. Serum Magnesium and Calcium Levels in Relation to Ischemic Stroke: Mendelian Randomization Study. Neurology. 2019.

54. Yuan Z, Wang P, Xie Y, et al. Association of Magnesium Depletion Score With Increased Stroke Incidence and Mortality Risks in a Comprehensive Analysis. Sci Rep. 2025.

55. Tong TYN, Appleby PN, Key TJ, et al. The Associations of Major Foods and Fibre With Risks of Ischaemic and Haemorrhagic Stroke: A Prospective Study of 418,329 Participants in the EPIC Cohort. Eur Heart J. 2020.

56. Monteiro CA, Louzada ML, Steele-Martinez E, et al. Ultra-Processed Foods and Human Health: The Main Thesis and the Evidence. Lancet. 2025.

57. Bhave VM, Oladele CR, Ament Z, et al. Associations Between Ultra-Processed Food Consumption and Adverse Brain Health Outcomes. Neurology. 2024.

58. Judd SE, Gutiérrez OM, Newby PK, et al. Dietary Patterns Are Associated With Incident Stroke and Contribute to Excess Risk of Stroke in Black Americans (REGARDS). Stroke. 2013.

59. Navale SS, Mulugeta A, Zhou A, Llewellyn DJ, Hyppönen E. Vitamin D and Brain Health: An Observational and Mendelian Randomization Study. Am J Clin Nutr. 2022.

60. Harris WS. The Omega-3 Index as a Risk Factor for Coronary Heart Disease. Am J Clin Nutr. 2008.

61. Harris WS, Del Gobbo L, Tintle NL. The Omega-3 Index and Relative Risk for Coronary Heart Disease Mortality: Estimation From 10 Cohort Studies. Atherosclerosis. 2017.

62. Harris WS, Tintle NL, Etherton MR, Vasan RS. Erythrocyte Long-Chain Omega-3 Fatty Acid Levels Are Inversely Associated With Mortality and With Incident Cardiovascular Disease: The Framingham Heart Study. J Clin Lipidol. 2017.

63. Franco WG, O'Keefe EL, O'Keefe JH, et al. Omega-3 Index Improves Upon the Pooled Cohort Equation in Predicting Risk for CVD. J Clin Lipidol. 2024.

64. O'Keefe JH, Tintle NL, Harris WS, et al. Omega-3 Blood Levels and Stroke Risk: A Pooled and Harmonized Analysis of 183,291 Participants From 29 Prospective Studies. Stroke. 2024.

65. Abdelhamid AS, Brown TJ, Brainard JS, et al. Omega-3 Fatty Acids for the Primary and Secondary Prevention of Cardiovascular Disease. Cochrane Database Syst Rev. 2020.

66. Gencer B, Djousse L, Al-Ramady OT, Cook NR, Manson JE, Albert CM. Effect of Long-Term Marine ω-3 Fatty Acids Supplementation on the Risk of Atrial Fibrillation in Randomized Controlled Trials: A Meta-Analysis. Circulation. 2021.

67. Argeros Z, Xu X, Bhandari B, et al. Magnesium Supplementation and Blood Pressure: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Hypertension. 2025.

68. Cunha AR, D'El-Rei J, Medeiros F, et al. Oral Magnesium Supplementation Improves Endothelial Function and Attenuates Subclinical Atherosclerosis in Thiazide-Treated Hypertensive Women. J Hypertens. 2017.

69. Saver JL, Starkman S, Eckstein M, et al. Prehospital Use of Magnesium Sulfate as Neuroprotection in Acute Stroke (FAST-MAG). N Engl J Med. 2015.

70. Pandey A, Patel MR, Willis B, et al. Association Between Midlife Cardiorespiratory Fitness and Risk of Stroke: The Cooper Center Longitudinal Study. Stroke. 2016.

71. Feldman DI, Al-Mallah MH, Keteyian SJ, et al. No Evidence of an Upper Threshold for Mortality Benefit at High Levels of Cardiorespiratory Fitness. J Am Coll Cardiol. 2015.

72. Billinger SA, Arena R, Bernhardt J, et al. Physical Activity and Exercise Recommendations for Stroke Survivors: A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke. 2014.

73. Ahmed S, Bogiatzi C, Hackam DG, et al. Vitamin B Deficiency and Hyperhomocysteinaemia in Outpatients With Stroke or Transient Ischaemic Attack: A Cohort Study at an Academic Medical Centre. BMJ Open. 2019.

Related at Fishtown Medicine

• ApoB and Heart Health - the cholesterol particle count that predicts heart attacks far better than standard LDL
• Lp(a): The 'Widowmaker' Genetic Risk - the genetic cholesterol particle that standard panels miss, present in 1 in 5 adults
• Lp(a) and Cholesterol - why you can have perfect cholesterol and still be at high risk
• ED and Cardiovascular Risk - erectile dysfunction as the earliest warning sign of vascular disease
• Should You Take a Daily Aspirin? - why routine aspirin for primary prevention is no longer advised
• Your Watch Flagged AFib: What to Do Next - AFib is a leading cause of stroke, and wearables now catch it

Medical Disclaimer

This article is for educational purposes only and is not medical advice for any individual. Stroke prevention is highly individual, and the right strategy depends on your specific risk factors, medication tolerances, and goals. Always discuss new medications, dose changes, or screening decisions with your physician.