A claim you hear on longevity podcasts

Does heart disease risk rise with an A1C above 5.1%?

Leaning for. Of 10 studies that test it, 5 partly agree, 4 agree and 1 disagrees.

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The claim checked: Heart disease risk climbs in a straight line once A1C passes 5.1% Hear it at 17:44

What do the studies say?

Leaning for

A1C is a blood test that shows your average blood sugar over the last few months. Four of ten studies agree that heart risk starts inside the normal range. One found it for men above 5%, and another between 4.6% and 6.0%. Five are mixed: they place the rise higher, at 5.5% or 6.0%, or find a J-shape, where risk is also higher at the lowest levels. One study of 26,563 women found A1C predicted diabetes but not heart disease. No study used the cut-off said on the episode.

Computed from 10 studies that test this point, each judged by two readers, in full. 5 more studies are waiting for a full read and do not count yet.

What was said on the podcast?

“Anybody over 5.1, the risk of cardiovascular disease went up in a linear fashion.”
Mark Hyman, The Doctor's Farmacy · Why Your Insulin Resistance Isn't Permanent (And How to Fix It) · 17:44 on YouTube
Episode check Heart risk climbs from a fasting blood sugar inside the normal range, the episode says. Four of seven studies disagree. 6 claims checked against 62 studies · 8 chapters not checked yet See the whole episode →
The point checked Leaning for

In adults without diabetes, cardiovascular disease risk rises with A1C above 5.1%, below the 5.7% prediabetes cut-off

Agree 4

other primary study · 2001 · landmark

“In the Norfolk cohort, the effect of HbA1c concentration on mortality was evident even at the lower end of the population distribution, and there was no apparent threshold effect: men with HbA1c concentrations above 5% had greater risk than men with concentrations below 5%.”

Glycated haemoglobin, diabetes, and mortality in men in Norfolk cohort of european prospective investigation of cancer and nutrition (EPIC-Norfolk). BMJ
Who: 4662 men aged 45-79 years in the EPIC-Norfolk cohort with HbA1c measured at baseline (includes 160 with self-reported diabetes)
PMID 11141143

other primary study · 2005

“Thus, HbA1c level is associated with CHD well into the “normal” range of HbA1c values (ie, between 4.6% and 6.0%).”

Glycemic control and coronary heart disease risk in persons with and without diabetes: the atherosclerosis risk in communities study. Arch Intern Med
Who: ARIC case-cohort of 1321 adults without diabetes (fasting glucose <126 mg/dL at two visits) plus a cohort of 1626 adults with diabetes
PMID 16157837

other primary study · 2013

“Even in these populations restricted to lower HbA 1c levels, we found that for every 0.5%‐increment increase in HbA 1c levels, the RR of CHD was 1.32 (95% CI 1.05 to 1.65) in women and 1.27 (95% CI 1.04 to 1.55) in men, and 1.29 (95% CI 1.11 to 1.50) when pooled.”

Hemoglobin a1c is associated with increased risk of incident coronary heart disease among apparently healthy, nondiabetic men and women. J Am Heart Assoc
Who: nested case-control studies in the Nurses' Health Study (women) and Health Professionals Follow-Up Study (men) without diabetes and with HbA1c <6.5%
PMID 23537807

other primary study · 2009

“The risk for CHD/stroke begins well within the “normal” range of HbA1c.”

Independent association of HbA(1c) and incident cardiovascular disease in people without diabetes. Obesity (Silver Spring)
Who: randomly selected adults aged ≥18 in the North West Adelaide Health Study free of diabetes at baseline and follow-up and without baseline CHD or stroke
PMID 19131940

Partly agree 5

trial or observed group · 2010 · landmark

“There was no significant association between the glycated hemoglobin value and the risk of coronary heart disease at glycated hemoglobin values of less than 5.0%, but as compared with that category, glycated hemoglobin values of 5.5% or higher were associated with a hazard ratio for coronary heart disease of 1.38 (95% confidence interval [CI], 1.22 to 1.56).”

Glycated hemoglobin, diabetes, and cardiovascular risk in nondiabetic adults. N Engl J Med
Who: 11,092 black or white middle-aged adults in the ARIC study without a history of diabetes or cardiovascular disease
PMID 20200384

pooled analysis · 2017

“Our data support that cardiovascular mortality is significantly increased when HbA1c levels are above 8.0% in the population with diabetes and above 6.0% in those without.”

Glycated haemoglobin A1c as a risk factor of cardiovascular outcomes and all-cause mortality in diabetic and non-diabetic populations: a systematic review and meta-analysis. BMJ Open
Who: observational cohort studies of adults (aged 25-90) with and without diabetes from 20 countries
PMID 28760792

other primary study · 2014

“In analyses adjusted for several conventional CVD risk factors, there were approximately J-shaped associations between each glycemia measure we studied and CVD risk (Figure 1).”

Glycated hemoglobin measurement and prediction of cardiovascular disease. JAMA
Who: individual-participant data from 73 prospective cohorts of adults without known diabetes or CVD (mean age 58, 49% women)
PMID 24668104

pooled analysis · 2010

“In contrast with findings for glucose concentration, the current meta-analysis has indicated a RR for CHD of 1.20 per 1% higher HbA 1c in people without diabetes.”

Markers of dysglycaemia and risk of coronary heart disease in people without diabetes: Reykjavik prospective study and systematic review. PLoS Med
Who: Reykjavik cohort (Icelandic adults without history of MI) plus 26 Western prospective cohorts of people without diabetes; HbA1c data from 9 studies
PMID 20520805

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trial or observed group · 2021

“In the present study, HbA 1c levels above the cut-off value of 36.6 mmol/mol (5.5%) were associated with cardiovascular diseases.”

Association of glycated hemoglobin A1c levels with cardiovascular outcomes in the general population: results from the BiomarCaRE (Biomarker for Cardiovascular Risk Assessment in Europe) consortium. Cardiovasc Diabetol
Who: six European population-based cohorts (BiomarCaRE) in Germany, Italy, Sweden and Norway; 32,496 without diabetes
PMID 34781939

Disagree 1

controlled trial · 2007

“In summary, we found that baseline HbA1c is an independent risk predictor for type 2 diabetes but not cardiovascular disease among healthy middle-aged and older women.”

Hemoglobin A1c predicts diabetes but not cardiovascular disease in nondiabetic women. Am J Med
Who: 26,563 US female health professionals aged ≥45 years without diagnosed diabetes or vascular disease (Women's Health Study)
PMID 17679132

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