Genes Associated with Heart Disease
Cardiovascular disease has strong genetic components—but lifestyle factors can override most genetic risk.
Genetics loads the gun. Lifestyle pulls the trigger.
Heart disease is highly heritable, but it's also highly preventable. In the INTERHEART study, 9 modifiable risk factors accounted for over 90% of heart attack risk across all populations. Your genes determine which factors matter most for you—not whether you'll get heart disease.
The genes.
Organized by the cardiovascular pathway they affect.
Lipid Metabolism
These genes affect how you process cholesterol, triglycerides, and other blood fats.
E4 increases cardiovascular risk; E2 may be protective but can raise triglycerides. APOE affects how you respond to dietary fat.
LDLR
LDL receptorRemoves LDL from blood. Familial hypercholesterolemia mutations cause very high LDL from birth.
PCSK9
LDL receptor degradationBreaks down LDL receptors. Loss-of-function variants are protective (lower LDL); gain-of-function raises LDL.
CETP
HDL-LDL cholesterol transferTransfers cholesterol between lipoproteins. Low activity variants have higher HDL.
APOB
LDL particle formationThe main protein on LDL particles. Mutations affect LDL levels and particle number.
Lipoprotein(a)
Lp(a) is a special lipoprotein that's almost entirely genetically determined. High Lp(a) is a major independent risk factor.
LPA
Lipoprotein(a) levelsLp(a) levels are ~90% genetically determined. High Lp(a) (>50 mg/dL) significantly increases cardiovascular and stroke risk.
Methylation & Homocysteine
Elevated homocysteine is a cardiovascular risk factor. These genes affect homocysteine levels.
Slow MTHFR can elevate homocysteine if folate/B12 are low. High homocysteine damages blood vessels.
Alternative pathway for clearing homocysteine. Variants affect balance between pathways.
Blood Clotting
These genes affect clotting tendency. Higher clotting = higher thrombosis risk.
Factor V Leiden
Clotting factorMost common inherited clotting disorder. Increases risk of deep vein thrombosis and pulmonary embolism.
Prothrombin (F2)
Clotting cascadeG20210A variant increases prothrombin levels, increasing clot risk.
PAI-1
Fibrinolysis inhibitorInhibits clot breakdown. 4G/4G variant = higher PAI-1 = clots persist longer.
Blood Pressure
Multiple genes affect blood pressure regulation. Most have modest individual effects.
ACE
Blood pressure regulationAngiotensin-converting enzyme. I/D polymorphism affects ACE levels and blood pressure response.
AGT
AngiotensinogenPrecursor to angiotensin. Variants affect baseline blood pressure and salt sensitivity.
ADD1
Sodium handlingAffects how kidneys handle sodium. Gly460Trp variant increases salt sensitivity.
Inflammation & Oxidation
Atherosclerosis is an inflammatory disease. These genes affect vascular inflammation.
PON1
LDL oxidation protectionProtects LDL from oxidation. Oxidized LDL is more atherogenic. Q192R affects activity.
IL-6
Inflammatory cytokinePro-inflammatory. High IL-6 associated with cardiovascular events.
CRP
C-reactive proteinInflammatory marker. Some variants cause higher baseline CRP levels.
The Lp(a) story.
Lipoprotein(a) is different from other risk factors. It's almost entirely genetic and often missed.
What makes Lp(a) unique
- • ~90% genetic: Diet and lifestyle barely affect levels
- • Not on standard lipid panels: You have to specifically request it
- • One-time test: Levels don't change much over life
- • ~20% of people have elevated Lp(a): Many don't know it
- • Independent risk: Adds risk on top of LDL cholesterol
If Lp(a) is elevated (>50 mg/dL)
- • Be more aggressive with other risk factors you CAN control
- • LDL targets may need to be lower than average
- • Niacin may lower Lp(a) modestly (discuss with doctor)
- • PCSK9 inhibitors reduce Lp(a) ~25-30%
- • New targeted therapies are in development
What actually matters.
These modifiable factors account for over 90% of heart attack risk worldwide.
Metabolic Health
Insulin resistance, metabolic syndrome, and diabetes dramatically increase cardiovascular risk regardless of genetics.
Blood Pressure
Hypertension is the leading modifiable risk factor. Managing blood pressure reduces risk even with genetic predisposition.
Inflammation
Chronic inflammation drives atherosclerosis. CRP, diet, stress, sleep, and infections all affect inflammatory status.
Smoking
The single most impactful modifiable factor. Quitting reduces risk within years regardless of genetic background.
Exercise
Regular physical activity improves nearly every cardiovascular risk factor: lipids, blood pressure, insulin sensitivity, inflammation.
Diet Quality
Whole foods, omega-3s, fiber, potassium. But the optimal diet varies by genotype (APOE4 needs different fat approach).
Genetics personalizes prevention.
Different genes mean different optimal strategies.
APOE4 carriers
May benefit from lower saturated fat intake. More sensitive to dietary cholesterol. Respond well to exercise and omega-3s.
MTHFR variants + high homocysteine
Active B vitamins (methylfolate, methylcobalamin) may normalize homocysteine. Avoid folic acid; get folate from food or active forms.
Factor V Leiden or high clotting risk
Extra caution with hormones, long flights, surgery. May need anticoagulation in certain situations. Discuss with hematologist.
Salt-sensitive genotypes (ADD1, AGT)
Sodium restriction more impactful for blood pressure. Potassium intake especially important. DASH diet may be particularly effective.
"Heart disease genes don't determine your fate. They tell you which prevention strategies matter most for you."← Back to all genes