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August 19, 2025

ACE I/D Gene Variant and Cardiovascular Risk: Insights from CardiaX

The ACE I/D polymorphism affects enzyme activity, hypertension, and cardiovascular disease risk. Learn how to interpret your CardiaX results and apply targeted lifestyle, supplement, peptide, and medication strategies.

ACE I/D Gene Variant and Cardiovascular Risk: Insights from CardiaX

ACE I/D Polymorphism: A Key Genetic Driver of Hypertension and Cardiovascular Disease

Introduction

The angiotensin-converting enzyme (ACE) gene, located on chromosome 17q23, is a critical regulator of the renin–angiotensin–aldosterone system (RAAS). This system maintains blood pressure and fluid balance.

The ACE insertion/deletion (I/D) polymorphism (rs1799752)—caused by the presence (insertion, I) or absence (deletion, D) of a 287 base pair Alu repeat in intron 16—profoundly influences ACE enzyme activity:

  • DD genotype: Highest ACE activity → increased angiotensin II and blood pressure.

  • II genotype: Lowest ACE activity → reduced angiotensin II, lower BP.

  • ID genotype: Intermediate activity.

Your CardiaX test includes ACE I/D because it is strongly linked to hypertension, left ventricular hypertrophy (LVH), heart failure, myocardial infarction (MI), and stroke risk.

ACE and Cardiovascular Physiology

  • Angiotensin I → Angiotensin II conversion: ACE converts Ang I into Ang II, a potent vasoconstrictor.

  • Vascular effects: Ang II increases vascular resistance, stimulates aldosterone, and promotes sodium retention.

  • Cardiac remodeling: Ang II and aldosterone stimulate fibrosis, LVH, and vascular stiffening.

  • Inflammation: Ang II increases oxidative stress and endothelial dysfunction.

ACE I/D Polymorphism and Clinical Implications

1. Hypertension

  • DD carriers are at highest risk for essential hypertension and salt sensitivity.

  • II carriers often exhibit lower blood pressure and may have protection against hypertension.

2. Coronary Artery Disease & MI

  • D allele is associated with increased risk of myocardial infarction and earlier onset CAD.

  • Greater plaque instability and higher oxidative burden.

3. Heart Failure

  • DD genotype linked with more severe LV remodeling, hypertrophy, and worse prognosis.

4. Athletic Performance

  • D allele: Linked to power/sprint performance.

  • I allele: Associated with endurance capacity.

What Increases ACE-Driven Risk?

  • High sodium diet: Potentiates RAAS activation.

  • Obesity and insulin resistance: Increase RAAS tone and vascular inflammation.

  • Sedentary lifestyle: Reduces vascular flexibility.

  • Chronic stress: Elevates sympathetic drive, augmenting RAAS activity.

  • Low potassium intake: Favors vasoconstriction.

How to Mitigate ACE I/D-Associated Risk

1. Lifestyle Strategies

  • Low-sodium, potassium-rich diet: Emphasize leafy greens, legumes, and fruits.

  • DASH or Mediterranean diet: Both reduce BP and improve endothelial function.

  • Exercise: Aerobic + resistance training lowers RAAS activity.

  • Weight optimization: Reduces vascular inflammation and improves BP control.

  • Stress management: Meditation and yoga reduce sympathetic activation.

2. Nutraceuticals

  • Omega 1300 — Omega 1300: Lowers inflammation, reduces BP.

  • CoQ10 Omega — CoQ10 Omega: Improves endothelial function.

  • Magnesium glycinate: Promotes vasodilation and BP stability.

  • Curcumin Complex — Curcumin Complex: Anti-inflammatory and antioxidant.

  • Vitamin D3/K2: Supports vascular health and RAAS modulation.

3. Peptide Therapies

  • BPC-157: Enhances vascular healing and reduces fibrosis.

  • MOTS-c: Improves insulin sensitivity and mitochondrial efficiency.

  • KPV: Reduces systemic inflammation driven by Ang II.

4. Medications

  • ACE inhibitors (lisinopril, enalapril): Particularly effective in DD carriers with high ACE activity.

  • ARBs (losartan, valsartan): Block downstream effects of Ang II.

  • MRAs (spironolactone, eplerenone): Counteract aldosterone-mediated fibrosis.

  • Beta-blockers: Reduce sympathetic overdrive in high-risk carriers. However, it is important to stick with the newer beta-blockers (nebivolol or carvedilol).

Case Example

A 58-year-old man with DD genotype on CardiaX presents with hypertension and LVH.

Plan:

  • Lifestyle: Sodium reduction, potassium-rich Mediterranean diet, exercise.

  • Supplements: Omega 1300, CoQ10 Omega, Curcumin Complex.

  • Medications: Started on ACE inhibitor and low-dose MRA.

  • Peptides: BPC-157 considered for vascular remodeling.

Outcome: Blood pressure reduced from 158/96 to 124/78 mmHg. Echocardiogram shows regression of LVH after 12 months.

The Bottom Line

The ACE I/D polymorphism is one of the most impactful genetic variants for hypertension and cardiovascular disease risk.

  • DD carriers: Highest risk, strongest benefit from ACE inhibitors and RAAS-modulating strategies.

  • II carriers: Lower risk, endurance advantage, but still benefit from lifestyle optimization.

  • ID carriers: Intermediate phenotype, require balanced strategies.

CardiaX testing helps identify high-risk carriers and tailor interventions across diet, supplements, peptides, and medications.

References

  1. Rigat B, et al. An insertion/deletion polymorphism in the ACE gene accounting for half the variance of serum enzyme levels. J Clin Invest. 1990.

  2. Cambien F, et al. Deletion polymorphism in the ACE gene as a risk factor for myocardial infarction. Nature. 1992.

  3. Staessen JA, et al. The insertion/deletion polymorphism of the ACE gene and cardiovascular disease. J Hypertens. 1997.

  4. Schunkert H, et al. Association between a deletion polymorphism of the ACE gene and left ventricular hypertrophy. N Engl J Med. 1994.