The book is only
the beginning.

Finding Plaque Before Symptoms Appear

Explore the imaging research discussed in Chapter 2 and how coronary plaque may be identified before symptoms develop.

Bundgaard H, García-Lunar I, Kofoed KF, Hasselbalch R, Pérez-García CN, Kunkel JB, Stæger FF, et al. Prevalence of Silent Atherosclerosis across Adult Life. N Engl J Med. Published online August 29, 2026. doi:10.1056 /NEJMoa2609059.

Why a Severe Blockage Is Not the Whole Story

Dig into the research behind plaque rupture and why the degree of arterial narrowing is only part of the cardiovascular-risk picture.

Ahmadi A, Argulian E, Leipsic J, Newby DE, Narula J. From Subclinical Atherosclerosis to Plaque Progression and Acute Coronary Events: JACC State-of-the-Art Review. J Am Coll Cardiol. 2019;74(12):1608-1617. doi: 10.1016/j.jacc.2019.08.012.

Why Rapid Treatment Matters During a Heart Attack

Explore the relationship between an interrupted blood supply, heart-muscle injury, and the urgency of emergency treatment.

Francone M, Bucciarelli-Ducci C, Carbone I, et al. Impact of primary coronary angioplasty delay on myocardial salvage, infarct size, and microvascular damage in patients with ST-segment elevation myocardial infarction: insight from cardiovascular magnetic resonance. J Am Coll Cardiol. 2009;54(23):2145-2153. doi:10.1016/j.jacc.2009.08.024.

The Story of Hank Gathers

Learn more about the basketball player discussed in the chapter and the heart condition associated with his sudden collapse.

ESPN. Remember LMU's Hank Gathers 30 years after his tragic death on the basketball court | E:60 [video]. YouTube. 2020. https://www.youtube. com/watch?v=Gk-GWuyx3G4

Diabetes and Metabolic Health in America

Explore the population estimates behind the chapter's discussion of diabetes and metabolic health.

Gwira JA, Fryar CD, Gu Q. Prevalence of Total, Diagnosed, and Undiagnosed Diabetes in Adults: United States, August 2021–August 2023. NCHS Data Brief. 2024;(516). doi:10.15620/cdc/165794. O’Hearn M, Lauren BN, Wong JB, Kim DD, Mozaffarian D. Trends and Disparities in Cardiometabolic Health Among U.S. Adults, 1999–2018. J Am Coll Cardiol. 2022;80(2):138–151. doi:10.1016/j.jacc.2022.04.046.

The Body's Stress and Recovery States

Explore the research relevant to the chapter's comparison between short periods of acute stress and time spent recovering.

Carravieri A, Müller MS, Yoda K, Hayama S-I, Yamamoto M. Dominant Parasympathetic Modulation of Heart Rate and Heart Rate Variability in a Wild-Caught Seabird. Physiol Biochem Zool. 2016;89(4):263-276. doi: 10.1086/686894.

Sleep, Sleep Apnea, and Cardiovascular Health

Find research on insufficient sleep and sleep apnea, including their associations with cardiovascular and other health outcomes.

Redline S, Azarbarzin A, Peker Y. Obstructive sleep apnoea heterogeneity and cardiovascular disease. Nat Rev Cardiol. 2023;20(8):560-573. doi: 10.1038/s41569-023-00846-6. Gottlieb DJ, Punjabi NM. Diagnosis and Management of Obstructive Sleep Apnea: A Review. JAMA. 2020;323(14):1389-1400. doi:10.1001/jama. 2020.3514.

Childhood Adversity and Later Heart Health

Explore research on adverse childhood experiences and their possible long-term associations with cardiovascular risk.

Suglia SF, Koenen KC, Boynton-Jarrett R, et al. Childhood and adolescent adversity and cardiometabolic outcomes: a scientific statement from the American Heart Association. Circulation. 2018;137(5):e15-e28. doi:10.1161 /CIR.0000000000000536.

Understanding the HbA1c Diabetes Threshold

Learn what the HbA1c test measures and explore the diagnostic threshold discussed in the chapter.

American Diabetes Association Professional Practice Committee for Diabetes. 2. Diagnosis and Classification of Diabetes: Standards of Care in Diabetes-2026. Diabetes Care. 2026;49(Suppl 1):S27-S49. doi:10.2337 /dc26-S002. Inzucchi SE. Clinical practice: diagnosis of diabetes. N Engl J Med. 2012; 367(6):542-550. doi:10.1056/NEJMcp1103643.

How Long Can Insulin Resistance Develop?

Explore research on how insulin resistance can precede an elevated blood-glucose result or a diabetes diagnosis.

Tabák AG, Herder C, Rathmann W, Brunner EJ, Kivimäki M. Prediabetes: a high-risk state for diabetes development. Lancet. 2012;379(9833):2279- 2290. doi:10.1016/S0140-6736(12)60283-9.

Prediabetes and Diabetes: How Common Are They?

Review the prevalence figures discussed in the chapter and the distinction between prediabetes and diabetes.

Gwira JA, Fryar CD, Gu Q. Prevalence of Total, Diagnosed, and Undiagnosed Diabetes in Adults: United States, August 2021–August 2023. NCHS Data Brief. 2024;(516). doi:10.15620/cdc/165794.

When the Heart Squeezes but Struggles to Relax

Explore heart failure with preserved ejection fraction and why a normal-looking measure of pumping strength does not tell the whole story.

Cannata A, McDonagh TA. Heart Failure with Preserved Ejection Fraction. N Engl J Med. 2025;392(2):173-184. doi:10.1056/NEJMcp2305181.

Insulin, Inflammation, and Heart Valves

Explore the proposed connections among insulin signaling, immune activity, and changes in heart- valve tissue.

Neeland IJ, Lim S, Tchernof A, et al. Metabolic syndrome. Nat Rev Dis Primers. 2024;10:77. doi:10.1038/s41572-024-00563-5. Small AM, Yutzey KE, Binstadt BA, et al. Unraveling the Mechanisms of Valvular Heart Disease to Identify Medical Therapy Targets: A Scientific Statement From the American Heart Association. Circulation. 2024;150(6): e109-e128. doi:10.1161/CIR.0000000000001254.

Meet the Endothelium: Your Arteries' Inner Lining

Learn about the thin layer of cells lining your arteries and the role it plays in healthy blood-vessel function.

Godo S, Shimokawa H. Endothelial Functions. Arterioscler Thromb Vasc Biol. 2017;37(9):e108-e114. doi:10.1161/ATVBAHA.117.309813.

Insulin Resistance and Blood- Vessel Function

Explore how insulin resistance may affect nitric- oxide signaling, blood-vessel relaxation, and cardiovascular risk.

Kim JA, Montagnani M, Koh KK, Quon MJ. Reciprocal relationships between insulin resistance and endothelial dysfunction: molecular and pathophysiological mechanisms. Circulation. 2006;113(15):1888-1904. doi: 10.1161/CIRCULATIONAHA.105.563213.

Oxidative Stress: What Happens When Defense Falls Behind

Learn what oxidative stress means and explore its relationship to cells, blood vessels, and mitochondria.

Li A, Zheng N, Ding X. Mitochondrial abnormalities: a hub in metabolic syndrome-related cardiac dysfunction caused by oxidative stress. Heart Fail Rev. 2022;27(4):1387-1394. doi:10.1007/s10741-021-10109-6. Murphy E, Ardehali H, Balaban RS, et al. Mitochondrial function, biology, and role in disease: a scientific statement from the American Heart Association. Circ Res. 2016;118(12):1960-1991. doi:10.1161/RES. 0000000000000104.

Why Blood-Vessel Health Matters Beyond the Heart

Explore the connections between vascular health and the organs served by the body's circulation.

Kim JA, Montagnani M, Koh KK, Quon MJ. Reciprocal relationships between insulin resistance and endothelial dysfunction: molecular and pathophysiological mechanisms. Circulation. 2006;113(15):1888-1904. doi: 10.1161/CIRCULATIONAHA.105.563213. Mechanick JI, Farkouh ME, Newman JD, Garvey WT. Cardiometabolic- based chronic disease, adiposity and dysglycemia drivers: JACC state-of- the-art review. J Am Coll Cardiol. 2020;75(5):525-538. doi:10.1016/j.jacc. 2019.11.044.

Blood-Sugar Spikes and the Artery's Protective Surface

Examine the research discussed in the chapter on acute glucose changes and the protective lining of blood vessels.

1. Nieuwdorp M, van Haeften TW, Gouverneur MCLG, et al. Loss of endothelial glycocalyx during acute hyperglycemia coincides with endothelial dysfunction and coagulation activation in vivo. Diabetes. 2006; 55(2):480-486. doi:10.2337/diabetes.55.02.06.db05-1103. 2. Astapenko D, Benes J, Pouska J, Lehmann C, Islam S, Cerny V. Endothelial glycocalyx in acute care surgery: what anaesthesiologists need to know for clinical practice. BMC Anesthesiol. 2019. doi:10.1186/s12871- 019-0896-2.

Visceral Fat and Sex-Hormone Signaling

Explore how fat tissue can influence hormone metabolism and feedback signals, particularly in men.

Lee AA, Den Hartigh LJ. Metabolic impact of endogenously produced estrogens by adipose tissue in females and males across the lifespan. Front Endocrinol (Lausanne). 2025;16:1682231. doi:10.3389/fendo. 2025.1682231.

Visceral Fat Is More Than Stored Energy

Learn how visceral fat participates in hormone signaling, inflammation, and the body's hunger and fullness cues.

Vasamsetti SB, Natarajan N, Sadaf S, Florentin J, Dutta P. Regulation of cardiovascular health and disease by visceral adipose tissue-derived metabolic hormones. J Physiol. 2023;601(11):2099-2120. doi:10.1113 /JP282728.

Ultra-Processed Foods and Cardiometabolic Health

Explore research examining associations between ultra-processed food intake, diabetes, and cardiovascular outcomes.

Lane MM, Gamage E, Du S, et al. Ultra-processed food exposure and adverse health outcomes: umbrella review of epidemiological meta- analyses. BMJ. 2024;384:e077310. doi:10.1136/bmj-2023-077310.

Making Sense of Fasting Glucose

Explore how fasting-glucose measurements are interpreted and the difference between diagnostic cutoffs and individual clinical goals.

American Diabetes Association Professional Practice Committee for Diabetes. 2. Diagnosis and classification of diabetes: Standards of Care in Diabetes—2026. Diabetes Care. 2026;49(Suppl 1):S27-S49. doi:10.2337 /dc26-S002.

When Normal Blood Sugar Masks High Insulin

Explore the compensatory rise in insulin that can occur when cells become less responsive to its signal.

Polonsky KS, Sturis J, Bell GI. Non-insulin-dependent diabetes mellitus—a genetically programmed failure of the beta cell to compensate for insulin resistance. N Engl J Med. 1996;334:777-783. doi:10.1056 /NEJM199603213341207.

Hormones and the Heart’s Electrical System

Explore how estrogen and progesterone may influence the heart’s electrical activity and why hormonal changes during perimenopause and menopause can sometimes coincide with palpitations or rhythm changes.

Tisdale JE, Jaynes HA, Overholser BR, et al. Influence of Oral Progesterone Administration on Drug-Induced QT Interval Lengthening: A Randomized, Double-Blind, Placebo-Controlled Crossover Study. JACC Clin Electrophysiol. 2016;2(7):765-774. doi:10.1016/j.jacep.2016.02.015.

The Women's Health Initiative and Hormone Therapy

Revisit the landmark research that reshaped discussions of menopausal hormone therapy and cardiovascular risk.

Rossouw JE, Anderson GL, Prentice RL, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial. JAMA. 2002;288(3):321-333. doi:10.1001/jama.288.3.321.

What the TRAVERSE Trial Studied

Explore the trial of testosterone therapy in men with low testosterone and elevated cardiovascular risk, including the outcomes it measured.

Lincoff AM, Bhasin S, Flevaris P, et al. Cardiovascular Safety of Testosterone-Replacement Therapy. N Engl J Med. 2023;389(2):107-117. doi:10.1056/NEJMoa2215025.

Bob Harper's Heart Attack and Lp(a)

Read more about the public story discussed in the chapter and why inherited cardiovascular risks can matter even for physically active people.

Harvard Health Publishing. A possible culprit in early heart attacks. September 1, 2018. Accessed October 8, 2026.

Hormone Therapy and Lp(a): What Has Been Studied?

Explore research on changes in lipoprotein(a) measurements during estrogen or testosterone therapy.

Espeland MA, Marcovina SM, Miller V, et al. Effect of postmenopausal hormone therapy on lipoprotein(a) concentration. PEPI Investigators. Postmenopausal Estrogen/Progestin Interventions. Circulation. 1998;97 (10):979-986. doi:10.1161/01.cir.97.10.979. Berglund L, Carlström K, Stege R, et al. Hormonal regulation of serum lipoprotein(a) levels: effects of parenteral administration of estrogen or testosterone in males. J Clin Endocrinol Metab. 1996;81(7):2633-2637. doi: 10.1210/jcem.81.7.8675589.

Estrogen Therapy and Lp(a)

Explore research on how estrogen-based hormone therapy may affect lipoprotein(a), or Lp(a), levels in postmenopausal women.

Salpeter SR, Walsh JME, Ormiston TM, et al. Meta-analysis: effect of hormone-replacement therapy on components of the metabolic syndrome in postmenopausal women. Diabetes Obes Metab. 2006;8(5):538-554. doi: 10.1111/j.1463-1326.2005.00545.x.

Testosterone Therapy and Lp(a)

Review research examining how testosterone therapy may influence lipoprotein(a), or Lp(a), levels in men.

Berglund L, Carlström K, Stege R, et al. Hormonal regulation of serum lipoprotein (a) levels: effects of parenteral administration of estrogen or testosterone in males. J Clin Endocrinol Metab. 1996;81(7):2633-2637. doi: 10.1210/jcem.81.7.8675589.

Lp(a): An Inherited Risk Factor

Learn what lipoprotein(a) is and why it differs from the cholesterol numbers on a standard lipid panel.

Kronenberg F, Mora S, Stroes ESG, et al. Lipoprotein(a) in atherosclerotic cardiovascular disease and aortic stenosis: a European Atherosclerosis Society consensus statement. Eur Heart J. 2022;43(39):3925-3946. doi: 10.1093/eurheartj/ehac361.

Progesterone, Sleep, and Heart Rhythm

Explore the chapter's discussion of progesterone, nervous-system signaling, sleep, and possible cardiovascular connections.

1. Nolan BJ, Liang B, Cheung AS. Efficacy of Micronized Progesterone for Sleep: A Systematic Review and Meta-analysis of Randomized Controlled Trial Data. J Clin Endocrinol Metab. 2021;106(4):e942-e951. doi:10.1210 /clinem/dgaa873. 2. Tisdale JE, Jaynes HA, Overholser BR, et al. Influence of Oral Progesterone Administration on Drug-Induced QT Interval Lengthening: A Randomized, Double-Blind, Placebo-Controlled Crossover Study. JACC Clin Electrophysiol. 2016;2(7):765-774. doi:10.1016/j.jacep.2016.02.015.

Estrogen and Blood-Vessel Health

Explore the role of estrogen in vascular function and the cardiovascular questions surrounding changes in estrogen levels.

Mauvais-Jarvis F, Lindsey SH. Metabolic benefits afforded by estradiol and testosterone in both sexes: clinical considerations. J Clin Invest. 2024;134 (17):e180073. doi:10.1172/JCI180073.

Testosterone, Muscle, and Cardiovascular Markers

Learn more about testosterone's relationship with lean muscle, energy, and the lipid marker Lp(a).

Mauvais-Jarvis F, Lindsey SH. Metabolic benefits afforded by estradiol and testosterone in both sexes: clinical considerations. J Clin Invest. 2024;134 (17):e180073. doi:10.1172/JCI180073. Berglund L, Carlström K, Stege R, et al. Hormonal regulation of serum lipoprotein (a) levels: effects of parenteral administration of estrogen or testosterone in males. J Clin Endocrinol Metab. 1996;81(7):2633-2637. doi: 10.1210/jcem.81.7.8675589.

Why Heart Cells Need So Many Mitochondria

Explore the heart's substantial energy requirements and the role mitochondria play in meeting them.

Hinton A Jr, Claypool SM, Neikirk K, et al. Mitochondrial Structure and Function in Human Heart Failure. Circ Res. 2024;135(2):372-396. doi: 10.1161/CIRCRESAHA.124.323800.

What Gut-Microbe Transplants Revealed in Mice

Explore the animal experiment described in the chapter and what it can, and cannot, tell us about metabolism in humans.

D'Haens GR, Jobin C. Fecal Microbial Transplantation for Diseases Beyond Recurrent Clostridium Difficile Infection. Gastroenterology. 2019;157(3):624- 636. doi:10.1053/j.gastro.2019.04.053.

Heart-Failure Medicines and Their Mechanisms

Explore the mechanisms discussed for established heart-failure treatments, including beta blockers and ACE inhibitors.

Patel J, Rassekh N, Fonarow GC, et al. Guideline-Directed Medical Therapy for the Treatment of Heart Failure with Reduced Ejection Fraction. Drugs. 2023;83(9):747-759. doi:10.1007/s40265-023-01887-4.

The Heart's Demand for Energy

Learn why the continuously working heart requires a reliable supply of cellular energy.

Wang Z, Ying Z, Bosy-Westphal A, et al. Specific metabolic rates of major organs and tissues across adulthood: evaluation by mechanistic model of resting energy expenditure. Am J Clin Nutr. 2010;92(6):1369-1377. doi: 10.3945/ajcn.2010.29885.

ATP: The Energy Currency of Life

Explore the molecule cells use to power essential functions, from human heartbeats to the activity of other living organisms.

Nath S. An account of a century of ATP research. Biosystems. 2025;256: 105527. doi:10.1016/j.biosystems.2025.105527.

The Gut Barrier and Immune Response

Explore the relationship between intestinal barrier function, substances crossing that barrier, and immune activation.

Di Vincenzo F, Del Gaudio A, Petito V, Lopetuso LR, Scaldaferri F. Gut microbiota, intestinal permeability, and systemic inflammation: a narrative review. Intern Emerg Med. 2024;19(2):275-293. doi:10.1007/s11739-023- 03374-w.

The Microbiome and Cardiovascular Conditions

Review research on gut-microbe patterns associated with blood pressure, heart failure, and abnormal heart rhythms.

Tang WHW, Bäckhed F, Landmesser U, Hazen SL. Intestinal Microbiota in Cardiovascular Health and Disease: JACC State-of-the-Art Review. J Am Coll Cardiol. 2019;73(16):2089-2102. doi:10.1016/j.jacc.2019.03.024.

Butyrate, Fuel, and Mitochondria

Explore how short-chain fatty acids, including butyrate, interact with cellular energy pathways.

Mietus-Snyder M, Perak AM, Cheng S, et al. Next Generation, Modifiable Cardiometabolic Biomarkers: Mitochondrial Adaptation and Metabolic Resilience: A Scientific Statement From the American Heart Association. Circulation. 2023;148(22):1827-1845. doi:10.1161/CIR.0000000000001185.

When Heart Failure Affects Relaxation and Filling

Learn about the form of heart failure in which the heart may squeeze normally but has difficulty relaxing and filling.

Cannata A, McDonagh TA. Heart Failure with Preserved Ejection Fraction. N Engl J Med. 2025;392(2):173-184. doi:10.1056/NEJMcp2305181.

The Bristol Stool Scale

See the reference tool mentioned in Chapter 7 for describing stool form and discussing digestive changes.

Blake MR, Raker JM, Whelan K. Validity and reliability of the Bristol Stool Form Scale in healthy adults and patients with diarrhoea-predominant irritable bowel syndrome. Aliment Pharmacol Ther. 2016;44(7):693-703. doi: 10.1111/apt.13746.

From Gut Bacteria to TMAO

Explore how gut microbes and the liver participate in TMAO production and why researchers study its association with cardiovascular outcomes.

Tang WHW, Bäckhed F, Landmesser U, Hazen SL. Intestinal Microbiota in Cardiovascular Health and Disease: JACC State-of-the-Art Review. J Am Coll Cardiol. 2019;73(16):2089-2102. doi:10.1016/j.jacc.2019.03.024.

CoQ10 and the Q-SYMBIO Trial

Explore the heart-failure supplementation trial discussed in the book, including its design and reported outcomes.

Mortensen SA, Rosenfeldt F, Kumar A, et al. The effect of coenzyme Q10 on morbidity and mortality in chronic heart failure: results from Q-SYMBIO: a randomized double-blind trial. JACC Heart Fail. 2014;2(6):641-649. doi: 10.1016/j.jchf.2014.06.008.

What Happens After You Take a Probiotic?

Explore questions about probiotic persistence, strain differences, and what supplementation can realistically accomplish.

Smolinska S, Popescu FD, Zemelka-Wiacek M. A Review of the Influence of Prebiotics, Probiotics, Synbiotics, and Postbiotics on the Human Gut Microbiome and Intestinal Integrity. J Clin Med. 2025;14(11):3673. doi: 10.3390/jcm14113673.

Diet and the Gut Microbiome

Explore research on the relationships between dietary patterns, processed foods, and the mix of microbes living in the gut.

Whelan K, Bancil AS, Lindsay JO, Chassaing B. Ultra-processed foods and food additives in gut health and disease. Nat Rev Gastroenterol Hepatol. 2024;21(6):406-427. doi:10.1038/s41575-024-00893-5.

Mediterranean and DASH Eating Patterns

Learn about two dietary approaches discussed in Chapter 8 and the evidence connecting them with cardiovascular health.

Pagidipati NJ, Taub PR, Ostfeld RJ, Kirkpatrick CF. Dietary patterns to promote cardiometabolic health. Nat Rev Cardiol. 2025;22(1):38-46. doi: 10.1038/s41569-024-01061-7.

Protecting Mitochondrial Membranes

Explore the chapter's discussion of antioxidants, fatty acids, and the structure and function of mitochondria.

Joshi A, Richard TH, Gohil VM. Mitochondrial phospholipid metabolism in health and disease. J Cell Sci. 2023;136(17):jcs260857. doi:10.1242/jcs. 260857.

ApoE Genetics and Nutrition

Explore the genetic variation discussed in the chapter and why individual responses to dietary approaches may differ.

Abou Khalil Y, Rabès JP, Boileau C, Varret M. APOE gene variants in primary dyslipidemia. Atherosclerosis. 2021;328:11-22. doi:10.1016/j. atherosclerosis.2021.05.007.

When Ketosis Goes Too Far

Explore why occasional fat burning is different from remaining in ketosis long term, and what the research says about possible effects on cholesterol, kidney stones, and bone health.

Acharya P, Acharya C, Thongprayoon C, et al. Incidence and Characteristics of Kidney Stones in Patients on Ketogenic Diet: A Systematic Review and Meta-Analysis. Diseases. 2021;9(2):39. doi:10.3390 /diseases9020039. Li J, He W, Wu Q, et al. Ketogenic diets and β-hydroxybutyrate in the prevention and treatment of diabetic kidney disease: current progress and future perspectives. BMC Nephrol. 2025;26(1):127. doi:10.1186/s12882- 025-04019-0.

Ancestry and Metabolic Risk

Explore research on metabolic patterns in South and Southeast Asian populations without assuming that ancestry determines an individual's health.

Volgman AS, Palaniappan LS, Aggarwal NT, et al. Atherosclerotic Cardiovascular Disease in South Asians in the United States: Epidemiology, Risk Factors, and Treatments: A Scientific Statement From the American Heart Association. Circulation. 2018;138(1):e1-e34. doi:10.1161/CIR. 0000000000000580.

Understanding Broken Heart Syndrome

Learn about Takotsubo cardiomyopathy, the condition commonly called broken heart syndrome.

Omerovic E, Redfors B. Takotsubo syndrome: pathophysiological insights and innovations in patient care. Nat Rev Cardiol. 2026;23(4):239-254. doi: 10.1038/s41569-025-01211-5.

Vagus-Nerve Stimulation and Blood Pressure

Explore the medical-device approach described in the chapter and what researchers have studied about vagus-nerve stimulation.

Konstam MA, Udelson JE, Mann DL, et al. Vagal Nerve Stimulation in Patients With Heart Failure and Reduced Ejection Fraction: The ANTHEM- HFrEF Trial. J Am Coll Cardiol. 2026;87(25):3490-3502. doi:10.1016/j.jacc. 2026.03.040.

Heart Medicines and the Stress Response

Explore how established cardiac medicines may interact with the body's sympathetic nervous- system activity.

Patel J, Rassekh N, Fonarow GC, et al. Guideline-Directed Medical Therapy for the Treatment of Heart Failure with Reduced Ejection Fraction. Drugs. 2023;83(9):747-759. doi:10.1007/s40265-023-01887-4.

The Vagus Nerve: A Two-Way Communication Route

Learn how the vagus nerve carries signals between the brain and organs and helps regulate automatic bodily functions.

Rajendran PS, Hadaya J, Khalsa SS, et al. The vagus nerve in cardiovascular physiology and pathophysiology: From evolutionary insights to clinical medicine. Semin Cell Dev Biol. 2024;156:190-200. doi:10.1016/j. semcdb.2023.01.001.

What Heart Rate Variability Measures

Learn why the intervals between heartbeats naturally vary and how HRV is used to describe that variation.

Goldberger JJ, Arora R, Buckley U, Shivkumar K. Autonomic Nervous System Dysfunction: JACC Focus Seminar. J Am Coll Cardiol. 2019;73(10): 1189-1206. doi:10.1016/j.jacc.2018.12.064.

Chronic Stress Hormones and the Body

Explore research on prolonged exposure to stress- related hormones and its possible effects on recovery and cellular function.

Agorastos A, Chrousos GP. The neuroendocrinology of stress: the stress- related continuum of chronic disease development. Mol Psychiatry. 2022;27 (1):502-513. doi:10.1038/s41380-021-01224-9.

Adrenaline and Blood Pressure

Explore how sympathetic activation can change blood-vessel tone and contribute to changes in blood pressure.

Floras JS. Epinephrine and the genesis of hypertension. Hypertension. 1992;19(1):1-18. doi:10.1161/01.hyp.19.1.1.

Stress Signaling and Inflammation

Explore research on how sympathetic nervous- system signals may affect inflammatory pathways.

Mohanta SK, Heron C, Klaus-Bergmann A, et al. Metabolic and Immune Crosstalk in Cardiovascular Disease. Circ Res. 2025;136(11):1433-1453. doi:10.1161/CIRCRESAHA.125.325496.

Stress Responses and Abnormal Heart Rhythms

Explore the relationship between adrenergic stimulation and rhythm disturbances, including atrial fibrillation.

Manolis AA, Manolis TA, Apostolopoulos EJ, et al. The role of the autonomic nervous system in cardiac arrhythmias: The neuro-cardiac axis, more foe than friend?. Trends Cardiovasc Med. 2021;31(5):290-302. doi: 10.1016/j.tcm.2020.04.011.

Nitric-Oxide Supplements and the Bigger Picture

Explore the questions raised in Chapter 9 about supplements intended to support nitric oxide and the broader factors that affect blood-vessel function.

Ushio-Fukai M, Ash D, Nagarkoti S, et al. Interplay Between Reactive Oxygen/Reactive Nitrogen Species and Metabolism in Vascular Biology and Disease. Antioxid Redox Signal. 2021;34(16):1319-1354. doi:10.1089/ars. 2020.8161.

Chronic Inflammation and Heart Structure

Explore the proposed connections between inflammatory activity, heart-muscle changes, and valve function.

Small AM, Yutzey KE, Binstadt BA, et al. Unraveling the Mechanisms of Valvular Heart Disease to Identify Medical Therapy Targets: A Scientific Statement From the American Heart Association. Circulation. 2024;150(6): e109-e128. doi:10.1161/CIR.0000000000001254.

Stress and Food Cravings

Explore how stress-related biological signals may influence cravings and appetite.

Adam TC, Epel ES. Stress, eating and the reward system. Physiol Behav. 2007;91(4):449-458. doi:10.1016/j.physbeh.2007.04.011.

Beta Blockers, ACE Inhibitors, and Heart Recovery

Explore the clinical treatments mentioned in Chapter 9 and the mechanisms through which they may support an injured heart.

Patel J, Rassekh N, Fonarow GC, et al. Guideline-Directed Medical Therapy for the Treatment of Heart Failure with Reduced Ejection Fraction. Drugs. 2023;83(9):747-759. doi:10.1007/s40265-023-01887-4.

Antidepressants and Long-Term Treatment

Explore research questions about antidepressant treatment duration, symptom response, and follow- up over time.

Rush AJ, Trivedi MH, Wisniewski SR, et al. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. Am J Psychiatry. 2006;163(11):1905-1917. doi: 10.1176/ajp.2006.163.11.1905.

What Is Grounding?

Explore the grounding practice described in Chapter 10 and the evidence questions surrounding its proposed effects.

Chevalier G, Sinatra ST, Oschman JL, Delany RM. Earthing (grounding) the human body reduces blood viscosity-a major factor in cardiovascular disease. J Altern Complement Med. 2013;19(2):102-110. doi:10.1089/acm. 2011.0820.

The Breath-Sips Exercise

Review the breathing technique described in the chapter and explore research on breathing patterns and short-term relaxation.

Vlemincx E, Severs L, Ramirez JM. The psychophysiology of the sigh: II: The sigh from the psychological perspective. Biol Psychol. 2022;173: 108386. doi:10.1016/j.biopsycho.2022.108386.

Controlled Cold Exposure

Explore research on brief cold exposure, physiological stress responses, and recovery, including relevant safety considerations.

Cain T, Brinsley J, Bennett H, et al. Effects of cold-water immersion on health and wellbeing: A systematic review and meta-analysis. PLoS One. 2025;20(1):e0317615. doi:10.1371/journal.pone.0317615.

Sleep Duration and Artery Health

Explore the study discussed in Chapter 11 on sleep duration and signs of arterial disease.

Domínguez F, Fuster V, Fernández-Alvira JM, et al. Association of Sleep Duration and Quality With Subclinical Atherosclerosis. J Am Coll Cardiol. 2019;73(2):134-144. doi:10.1016/j.jacc.2018.10.060.

What Happens When Blood Pressure Doesn't Dip at Night?

Learn about nighttime blood-pressure patterns and the cardiovascular questions associated with non- dipping.

Huart J, Persu A, Lengelé JP, et al. Pathophysiology of the Nondipping Blood Pressure Pattern. Hypertension. 2023;80(4):719-729. doi:10.1161 /HYPERTENSIONAHA.122.19996.

The Timing of Heart Attacks and Sleep Apnea

Explore research on when heart attacks occur and how sleep apnea may affect nighttime cardiovascular stress.

Wang Y, Buayiximu K, Zhu T, et al. Day-night pattern of acute ST-segment elevation myocardial infarction onset in patients with obstructive sleep apnea. J Clin Sleep Med. 2024;20(5):765-775. doi:10.5664/jcsm.10990.

Sleep Apnea and Nighttime Bathroom Trips

Explore the relationship between sleep-disordered breathing, hormone signaling, and waking to urinate.

Chung YH, Kim JR, Choi SJ, Joo EY. Prevalence and predictive factors of nocturia in patients with obstructive sleep apnea syndrome: a retrospective cross-sectional study. PLoS One. 2022;17(4):e0267441. doi:10.1371 /journal.pone.0267441. Vrooman OPJ, van Kerrebroeck PEV, van Balken MR, van Koeveringe GA, Rahnama'i MS. Nocturia and obstructive sleep apnoea. Nat Rev Urol. 2024; 21(12):735-753. doi:10.1038/s41585-024-00887-7.

Why Sleep Apnea Can Cause Nighttime Urination

Learn how repeated breathing disruptions during sleep can trigger hormonal changes, including increases in atrial natriuretic peptide (ANP), that may contribute to frequent nighttime urination.

Vrooman OPJ, van Kerrebroeck PEV, van Balken MR, van Koeveringe GA, Rahnama'i MS. Nocturia and obstructive sleep apnoea. Nat Rev Urol. 2024; 21(12):735-753. doi:10.1038/s41585-024-00887-7.

From Snoring to Sleep Apnea

Learn how snoring, partial airway obstruction, obstructive sleep apnea, and central sleep apnea differ.

Lévy P, Kohler M, McNicholas WT, et al. Obstructive sleep apnoea syndrome. Nat Rev Dis Primers. 2015;1:15015. doi:10.1038/nrdp.2015.15. Redline S, Azarbarzin A, Peker Y. Obstructive sleep apnoea heterogeneity and cardiovascular disease. Nat Rev Cardiol. 2023;20(8):560-573. doi: 10.1038/s41569-023-00846-6.

Understanding AHI in Adults and Children

Learn how the apnea-hypopnea index is used to classify obstructive sleep apnea, including the different thresholds used for adults and children.

Gottlieb DJ, Punjabi NM. Diagnosis and Management of Obstructive Sleep Apnea: A Review. JAMA. 2020;323(14):1389-1400. doi:10.1001/jama. 2020.3514.

Sleep and the Body's Waste- Clearance Systems

Explore what researchers know about waste clearance during sleep and the distinction between the lymphatic and glymphatic systems.

Hablitz LM, Nedergaard M. The Glymphatic System: A Novel Component of Fundamental Neurobiology. J Neurosci. 2021;41(37):7698-7711. doi: 10.1523/JNEUROSCI.0619-21.2021.

Sleep Apnea and Nitric-Oxide Signaling

Explore how disrupted breathing during sleep may affect blood-vessel signaling and function.

Wu ZH, Tang Y, Niu X, Sun HY. The role of nitric oxide (NO) levels in patients with obstructive sleep apnea-hypopnea syndrome: a meta-analysis. Sleep Breath. 2021;25(1):9-16. doi:10.1007/s11325-020-02095-0.

Why Eight Hours in Bed May Not Mean Restorative Sleep

Explore the factors discussed in Chapter 11 that can interrupt sleep quality even when the clock suggests enough time in bed.

Baranwal N, Yu PK, Siegel NS. Sleep physiology, pathophysiology, and sleep hygiene. Prog Cardiovasc Dis. 2023;77:59-69. doi:10.1016/j.pcad. 2023.02.005.

Can Early Sleep-Disordered Breathing Improve?

Explore approaches mentioned for mild breathing- related sleep disturbances and when clinical assessment is needed.

Courtney R. Breathing retraining in sleep apnoea: a review of approaches and potential mechanisms. Sleep Breath. 2020;24(4):1315-1325. doi: 10.1007/s11325-020-02013-4.

Exercise, Food, and the Need for Recovery

Explore the case discussion in Chapter 12 about balancing training, nutrition, and rest rather than simply doing more.

Baranwal N, Yu PK, Siegel NS. Sleep physiology, pathophysiology, and sleep hygiene. Prog Cardiovasc Dis. 2023;77:59-69. doi:10.1016/j.pcad. 2023.02.005.

The Best Bedroom Temperature for Sleep

Explore how bedroom temperature can affect sleep quality and why a cooler sleeping environment, often around 68 to 72 degrees, may help support more restful sleep.

Baniassadi A, Manor B, Yu W, Travison T, Lipsitz L. Nighttime ambient temperature and sleep in community-dwelling older adults. Sci Total Environ. 2023;899:165623. doi:10.1016/j.scitotenv.2023.165623.

Magnesium Intake in the United States

Explore population research on magnesium intake and how deficiency estimates are defined.

Jiao K, Costello R, Gahche J, Rosanoff A, Wallace TC. Serum Magnesium Concentrations in the United States-An Updated Population Reference Interval in Children and Adults. J Nutr. 2026;156(6):101539. doi:10.1016/j. tjnut.2026.101539.

Broccoli, Sulforaphane, and Cellular Repair

Explore the research questions behind the chapter's discussion of broccoli compounds and cellular protective responses.

Vermeulen M, Klöpping-Ketelaars IWAA, van den Berg R, Vaes WHJ. Bioavailability and kinetics of sulforaphane in humans after consumption of cooked versus raw broccoli. J Agric Food Chem. 2008;56(22):10505-10509. doi:10.1021/jf801989e. Houghton CA. Sulforaphane: Its “Coming of Age” as a Clinically Relevant Nutraceutical in the Prevention and Treatment of Chronic Disease. Oxid Med Cell Longev. 2019;2019:2716870. doi:10.1155/2019/2716870 PMID: 31737167

Sleep Aids and Long-Term Cognitive Health

Explore research on long-term use of diphenhydramine and other anticholinergic medicines in relation to cognitive outcomes.

Gray SL, Anderson ML, Dublin S, et al. Cumulative use of strong anticholinergics and incident dementia: a prospective cohort study. JAMA Intern Med. 2015;175(3):401-407. doi:10.1001/jamainternmed.2014.7663.

Why Caffeine Affects Sleep Differently

Explore how differences in caffeine metabolism can change the timing and duration of its effects.

Cornelis MC, Kacprowski T, Menni C, et al. Genome-wide association study of caffeine metabolites provides new insights to caffeine metabolism and dietary caffeine-consumption behavior. Hum Mol Genet. 2016;25(24):5472- 5482. doi:10.1093/hmg/ddw334.

Understanding 4-7-8 Breathing

Explore the breathing pattern introduced in Chapter 12 and what is known about its use in relaxation routines.

Avcık FE, Koç F, Aktop A. Acute Psychophysiological Effects Of 4-7-8 And Nadi Shodhana Breathing: A Randomized Crossover Study. Appl Psychophysiol Biofeedback. 2026. Published online September 22, 2026. doi:10.1007/s10484-026-09811-8.

Magnesium and Sleep

Explore the biological role of magnesium and the evidence questions surrounding supplements for sleep.

Khosropanah A, Hosseini SA, Keshavarz A. Nutritional modulators of sleep: A narrative review of vitamins, minerals, amino acids, and their neurobiological and chronoepigenetic mechanisms. Chronobiol Int. 2026;43 (7):951-964. doi:10.1080/07420528.2026.2648011.

At-Home Testing for Sleep Apnea

Learn about the home-testing approach discussed in the chapter and how it differs from an in- laboratory sleep study.

Resmed. NightOwl: home sleep apnea test. Accessed October 8, 2026. Gottlieb DJ, Punjabi NM. Diagnosis and Management of Obstructive Sleep Apnea: A Review. JAMA. 2020;323(14):1389-1400. doi:10.1001/jama. 2020.3514.

Treatment Options for Sleep- Disordered Breathing

Explore the range of treatment approaches referenced in Chapter 12 and why evaluation matters when choosing among them.

Gottlieb DJ, Punjabi NM. Diagnosis and Management of Obstructive Sleep Apnea: A Review. JAMA. 2020;323(14):1389-1400. doi:10.1001/jama. 2020.3514.

Sleep Quality and Pain Sensitivity

Explore research on the relationship between disrupted sleep and how the body experiences pain.

Ağargün MY, Tekeoğlu I, Güneş A, Adak B, Kara H, Ercan M. Sleep quality and pain threshold in patients with fibromyalgia. Compr Psychiatry. 1999;40 (3):226-228. doi:10.1016/S0010-440X(99)90008-1. Medic G, Wille M, Hemels MEH. Short- and long-term health consequences of sleep disruption. Nat Sci Sleep. 2017;9:151-161. doi:10.2147/NSS. S134864.

Air Pollution and Cardiovascular Disease

Explore population research on air-pollution exposure and its contribution to cardiovascular illness and mortality.

Blaustein JR, Quisel MJ, Hamburg NM, Wittkopp S. Environmental Impacts on Cardiovascular Health and Biology: An Overview. Circ Res. 2024;134(9): 1048-1060. doi:10.1161/CIRCRESAHA.123.323613.

Living Near Major Roads and Heart Risk

Explore studies examining traffic-related exposure and cardiovascular outcomes among people living close to busy roads.

Xu J, Wang X, Zhang GW, Ma Y, Zang S. Association between residential proximity to major roadways and nonfatal cardiovascular disease in Chinese older adults: a nationwide study. Sci Rep. 2025. Published online July 2, 2025. doi:10.1038/s41598-025-08298-3.

Lead Exposure and Cardiovascular Health

Explore research linking lead exposure with blood pressure, arterial disease, and heart-rhythm outcomes.

1. Tsoi MF, Lo CWH, Cheung TT, Cheung BMY. Blood lead level and risk of hypertension in the United States National Health and Nutrition Examination Survey 1999-2016. Sci Rep. 2021;11(1):3010. doi:10.1038/s41598-021- 82435-6. 2. Lamas GA, Bhatnagar A, Jones MR, et al. Contaminant Metals as Cardiovascular Risk Factors: A Scientific Statement From the American Heart Association. J Am Heart Assoc. 2023;12(13):e029852. doi:10.1161 /JAHA.123.029852.

Understanding Adverse Childhood Experiences

Learn about the ACE framework for describing categories of childhood adversity and the research behind it.

Godoy LC, Frankfurter C, Cooper M, et al. Association of Adverse Childhood Experiences With Cardiovascular Disease Later in Life: A Review. JAMA Cardiol. 2021;6(2):228-235. doi:10.1001/jamacardio. 2020.6050.

How Certain Heavy Metals Interact With Cells

Explore the biological mechanisms discussed in Chapter 13, including how some metals may interfere with normal mineral-dependent processes.

Lamas GA, Bhatnagar A, Jones MR, et al. Contaminant Metals as Cardiovascular Risk Factors: A Scientific Statement From the American Heart Association. J Am Heart Assoc. 2023;12(13):e029852. doi:10.1161 /JAHA.123.029852.

Pesticide-Residue Food Lists

Find the annual food lists mentioned in the chapter and learn what they measure and how to interpret them.

Environmental Working Group. The 2026 Dirty Dozen. EWG’s Shopper’s Guide to Pesticides in Produce. 2026. Accessed October 8, 2026. Environmental Working Group. The 2026 Clean Fifteen. EWG’s Shopper’s Guide to Pesticides in Produce. 2026. Accessed October 8, 2026.

BPA: Where It's Found and Why It's Studied

Explore the chemical discussed in Chapter 13, its uses, and research questions about human exposure.

Vogel SA. The politics of plastics: the making and unmaking of bisphenol A "safety". Am J Public Health. 2009;99 Suppl 3:S559-S566. doi:10.2105 /AJPH.2008.159228.

PFAS and Long-Lasting Environmental Chemicals

Learn what PFAS are, where exposure may occur, and what researchers are investigating about possible health effects.

Schlezinger JJ, Gokce N. Perfluoroalkyl/Polyfluoroalkyl Substances: Links to Cardiovascular Disease Risk. Circ Res. 2024;134(9):1136-1159. doi: 10.1161/CIRCRESAHA.124.323697. Qin Y, Yuan X, Cui Z, et al. Low dose PFDA induces DNA damage and DNA repair inhibition by promoting nuclear cGAS accumulation in ovarian epithelial cells. Ecotoxicol Environ Saf. 2023;265:115503. doi:10.1016/j. ecoenv.2023.115503.

Synthetic Fabrics and Chemical Exposure

Explore the chapter's questions about chemicals associated with performance fabrics, possible exposure routes, and the limits of current evidence.

Li K, Sun X, Qian Y, et al. Sweat-amplified dermal transfer and combined toxicity of per- and polyfluoroalkyl substances and organophosphate esters mixtures in children's textiles. Sci Total Environ. 2025;1000:180426. doi: 10.1016/j.scitotenv.2025.180426.

Noise Exposure, Stress, and the Heart

Explore research on environmental noise, stress responses, and possible cardiovascular effects.

Miller MR, Landrigan PJ, Arora M, et al. Water, Soil, Noise, and Light Pollution: JACC Focus Seminar, Part 2. J Am Coll Cardiol. 2024;83(23): 2308-2323. doi:10.1016/j.jacc.2024.03.421.

Light Exposure and the Body Clock

Learn how light-sensitive pathways help regulate daily rhythms and why nighttime light exposure is being studied.

Knutson KL, Dixon DD, Grandner MA, et al. Role of Circadian Health in Cardiometabolic Health and Disease Risk: A Scientific Statement From the American Heart Association. Circulation. 2025;152(21):e408-e419. doi: 10.1161/CIR.0000000000001388.

Work Stress, Sports, and Acute Cardiac Events

Explore studies on job strain, long work hours, emotionally intense events, and cardiovascular outcomes.

Virtanen M, Kivimäki M. Long working hours and risk of cardiovascular disease. Curr Cardiol Rep. 2018;20(11):123. doi:10.1007/s11886-018-1049- 9. Wilbert-Lampen U, Leistner D, Greven S, et al. Cardiovascular events during World Cup soccer. N Engl J Med. 2008;358(5):475-483. doi:10.1056 /NEJMoa0707427.

Chronic Stress, Inflammation, and Autoimmune Disease

Explore research on chronic stress, stress-related disorders, inflammation, and associations with autoimmune disease, including systemic lupus erythematosus.

Song H, Fang F, Tomasson G, et al. Association of Stress-Related Disorders With Subsequent Autoimmune Disease. JAMA. 2018;319(23): 2388-2400. doi:10.1001/jama.2018.7028. Roberts AL, Malspeis S, Kubzansky LD, et al. Association of Trauma and Posttraumatic Stress Disorder With Incident Systemic Lupus Erythematosus in a Longitudinal Cohort of Women. Arthritis Rheumatol. 2017;69(11):2162- 2169. doi:10.1002/art.40222.

Chelation Therapy: What the Trials Examined

Explore the cardiovascular chelation trials mentioned in Chapter 14, including why the results require careful interpretation.

Lamas GA, Anstrom KJ, Navas-Acien A, et al. Edetate Disodium-Based Chelation for Patients With a Previous Myocardial Infarction and Diabetes: TACT2 Randomized Clinical Trial. JAMA. 2024;332(10):794-803. doi: 10.1001/jama.2024.11463.

How the Liver Processes and Eliminates Substances

Learn about the metabolic pathways and transport processes involved when the liver helps the body process substances.

Almazroo OA, Miah MK, Venkataramanan R. Drug Metabolism in the Liver. Clin Liver Dis. 2017;21(1):1-20. doi:10.1016/j.cld.2016.08.001.

Choosing a Water-Filtering Approach

Explore the chapter's discussion of household filtration and the contaminants different systems may be designed to reduce.

Bonanni LJ, Newman JD. Personal Strategies to Reduce the Cardiovascular Impacts of Environmental Exposures. Circ Res. 2024;134 (9):1197-1217. doi:10.1161/CIRCRESAHA.123.323624.

Microplastics and Everyday Exposure

Explore where microplastic exposure can occur and what emerging research is investigating about health outcomes.

Marfella R, Prattichizzo F, Sardu C, et al. Microplastics and Nanoplastics in Atheromas and Cardiovascular Events. N Engl J Med. 2024;390(10):900- 910. doi:10.1056/NEJMoa2309822.

Sweating and the Body's Elimination Pathways

Explore the evidence questions behind the chapter's discussion of sweating, sauna use, and metal elimination.

Genuis SJ, Birkholz D, Rodushkin I, Beesoon S. Blood, urine, and sweat (BUS) study: monitoring and elimination of bioaccumulated toxic elements. Arch Environ Contam Toxicol. 2011;61(2):344-357. doi:10.1007/s00244- 010-9611-5.

Dietary Fiber and Elimination

Learn how fiber supports digestive function and explore the role of the gut in processing and eliminating substances.

Zhang N, Huang C, Ou S. In vitro binding capacities of three dietary fibers and their mixture for four toxic elements, cholesterol, and bile acid. J Hazard Mater. 2011;186(1):236-239. doi:10.1016/j.jhazmat.2010.10.120.

EMDR and Trauma Treatment

Explore the therapeutic approach mentioned in the chapter and the questions involved in comparing trauma treatments.

de Jongh A, de Roos C, El-Leithy S. State of the science: Eye movement desensitization and reprocessing (EMDR) therapy. J Trauma Stress. 2024; 37(2):205-216. doi:10.1002/jts.23012.

The HEART Framework in Clinical Practice

Explore the book's proposal for considering the HEART domains alongside established cardiovascular care.

How Long Does It Take to Form a Habit?

Explore behavioral research on the time and repetition involved in developing new routines.

Lally P, van Jaarsveld CHM, Potts HWW, Wardle J. How are habits formed: modelling habit formation in the real world. Eur J Soc Psychol. 2010;40:998- 1009. doi:10.1002/ejsp.674.