Hematocrit and the risk of coronary heart disease mortality

doi:10.1067/mhj.2001.118467

American Heart Journal

Volume 142, Issue 4, October 2001, Pages 657-663

https://doi.org/10.1067/mhj.2001.118467 Get rights and content

Abstract

Background An association between hematocrit (Hct) and coronary heart disease (CHD) mortality has been previously observed. However, the relationship of Hct and CHD independent of other cardiovascular disease (CVD) risk factors and differences between men and women remain unclear. Methods We examined the association between Hct and CHD mortality with Cox regression analyses of data from 8896 adults, aged 30-75 years, in the Second National Health and Nutrition Examination Survey (NHANES II) Mortality Study (1976-1992). Covariates included age, sex, race, education, smoking status, hypertensive status, total serum cholesterol, body mass index, white blood cell count, and history of CVD and diabetes. Hct was categorized by use of sex-specific tertiles, and all analyses were stratified by sex. Results During 16.8 years of follow-up, there were 545 (men 343, women 202) deaths from CHD (International Classification of Diseases, 9th revision [ICD-9] 410–414), 778 (men 426, women 279) deaths from diseases of the heart (ICD-9 390-398, 402, 404, 410-414, 415-417, 420-429), and 2046 (men 1216, women 830) all-cause deaths. Among men, the crude CHD mortality rate per 10,000 population was 42.6, 31.9, and 46.3 among those with Hct in the lower, middle, and upper tertiles, respectively. The corresponding crude CHD mortality rates among women were 12.6, 18.6, and 27.7. After adjustment for age and other CVD risk factors, there was no association between Hct in the upper tertile compared with the lower tertile and mortality from either CHD, diseases of the heart, or all causes among men. Women with Hct in the upper tertile were 1.3 times (95% CI 0.9–1.9) more likely to die from CHD than were women with Hct in the lowest tertile, after multivariate adjustment. The effect of high Hct on CHD mortality among women younger than 65 years of age was slightly stronger (relative risk 2.2, 95% CI 1.0–4.6). Conclusions These results suggest that the association between Hct and mortality from CHD and all causes is complex, differing both by sex and age. Further research is needed to gain a better understanding of these age and sex differences. (Am Heart J 2001;142:657-63.)

Section snippets

Methods

The National Center for Health Statistics of the Centers for Disease Control and Prevention conducted NHANES II between February 1976 and February 1980. NHANES II, a nationwide probability sample of approximately 28,000 persons, was designed to be representative of the civilian, noninstitutionalized population of the United States aged 6 months to 74 years. A detailed description of the NHANES II survey and sampling procedures has been provided elsewhere.²⁰

Briefly, data were collected through

Results

The mean Hct for men (44.1, SE 0.07) and women (40.1, SE 0.08) differed significantly (P <.01), suggesting 2 different underlying distributions of Hct for the sex groups. Therefore baseline characteristics by Hct are shown in Table I separately for men and women.

. Characteristics of 4213 men and 4683 women by sex-specific tertiles of Hct: NHANES II Mortality Study

Empty Cell	Hct 19.0-43.0 (n = 1629)	Hct 43.2-45.2 (n = 1220)	Hct 45.5-61.7 (n = 1364)	Hct 14.5-39.0 (n = 1706)	Hct 39.2-41.5 (n = 1528)	Hct
Empty Cell	Men			Women

Discussion

Consistent with the findings of previous studies, our results indicate that elevated Hct is associated with several CVD risk factors, including cigarette smoking, blood pressure, and total cholesterol. In addition, the association between Hct and mortality is different for men and women. Crude mortality rates among men suggest a nonlinear relationship between Hct and mortality from CHD, diseases of the heart, and all causes; however, these associations were not apparent after adjustment for CVD

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Familial hypercholesterolemia (FH) is a genetic disease associated with an important risk of premature and recurrent atherosclerotic cardiovascular disease (ASCVD). Red blood cell (RBC) parameters such as cell count and hematocrit (HCT) have previously been associated with ASCVD risk in the general population. However, little is known concerning their effect in FH. The aim of the present study is to investigate the effect of the different RBC parameters on the incidence of major adverse cardiovascular events (MACE) in FH patients.
In this prospective cohort study, genetically-confirmed FH patients aged between 18 and 65 years and without history of a prior ASCVD event were included. MACE included myocardial infarction, stroke, coronary revascularization, unstable angina or cardiovascular death.
A total of 482 subjects (6217 person-years of follow-up) were included in the analysis. Hemoglobin (HB), RBC count, and HCT were significant predictors of MACE risk (HR 1.04 (95% CI 1.01–1.06) p = 0.001, HR 2.69 (95% CI 1.49–4.86) p = 0.001, and HR 1.16 (95% CI 1.08–1.26) p < 0.0001, respectively) and these associations remained significant when adjusted for traditional cardiovascular risk factors. In addition, the frequency of recurrent MACE was 4-fold and 7-fold higher in the group above vs below the median for HB (p = 0.002) and RBC count (p = 0.001), respectively.
HB, RBC count and HCT were significant predictors of incident and recurring MACE in FH patients. These parameters could therefore be used to further refine the ASCVD risk prediction in this vulnerable population.
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Anemia is a known adverse prognostic factor among patients with cardiovascular diseases. We investigated whether the hemoglobin level was associated with the rhythm outcome after atrial fibrillation (AF) catheter ablation (AFCA).
We included 2627 patients who underwent AFCA and a guidelines-based rhythm follow-up (age 58 ± 10.9 years, 73% men, 30.6% with persistent AF), and evaluated the association of pre-AFCA anemia (haemoglobin <13 g/dL in men and <12 g/dL in women) and rhythm outcomes. We studied the mechanistic relationship between anemia and AF recurrence using a Mendelian randomization analysis (1775 subjects with genome-wide association study) after reviewing already proven 12 hemoglobin-associated genetic polymorphisms.
The body mass index, paroxysmal AF, warfarin use, and baseline red cell distribution width were independently associated with anemia in patients with AF. During a 23-month follow-up (interval OR 9–48 months), the clinical AF recurrence rate was significantly higher in patients with than without anemia (log-rank p = 0.001; propensity score-matched log-rank p = 0.004). This pattern was more significant in male patients (Log-rank p < 0.001) or patients with paroxysmal AF (Log-rank p < 0.001). Anemia (hazard ratio [HR] 1.45 [1.17–1.80], p = 0.001), left atrial diameter (HR 1.03 [1.01–1.04], p < 0.001), a female sex (HR 1.17 [1.00–1.36], p = 0.047), and persistent AF (HR 1.58 [1.36–1.84], p < 0.001) were independently associated with post-AFCA clinical recurrence. In the Mendelian randomization, we could not find a significant direct causal relationship between anemia and AF recurrence at the genetic level.
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Citation Excerpt :
Whether an elevated hemoglobin concentration in individuals without PV, and thus presumably without PV-related procoagulative changes, is associated with an increased risk of vascular events is less clear. Several authors have reported increased risks of both arterial thrombosis and venous thrombosis in individuals with elevated hematocrit in large prospective cohort studies [4–11]. For example, Wannamethee et al. reported that men with an elevated hematocrit >50% were at a 2.5-fold higher risk of ischemic stroke and Kunnas et al. reported that a hematocrit of ≥50% was an independent risk factor for cardiovascular disease and was also associated with a poorer overall survival [5–12].
There are conflicting results whether elevated hematocrit is associated with an increased risk of thromboembolic events in individuals without polycythemia vera. To assess the risk of vascular events in relation to hemoglobin concentration, we conducted a large population-based cohort study based on Scandinavian health registers.
We included 1,538,019 Swedish and Danish blood donors between 1987 and 2012. Hazard ratios (HRs) of arterial and venous thrombosis were estimated using Cox regression. Additionally, we fitted person-stratified models where each donor was compared only to him-/herself.
The risk of myocardial infarction and ischemic stroke increased with higher hemoglobin concentration in both men and women. The HRs for myocardial infarction and ischemic stroke in men with hemoglobin concentration ≥ 17.5 g/dL were 3.52 (95% confidence interval [CI], 2.85–4.36) and 2.36 (95% CI, 1.63–3.43), respectively, compared to the reference group. The corresponding HRs for women with hemoglobin concentration ≥ 16.0 g/dL were 3.22 (2.12–4.89) and 2.35 (1.37–4.02) for myocardial infarction and ischemic stroke, respectively. The risk of venous thrombosis was highest in men with subnormal hemoglobin concentration (<13.0 g/dL), HR 1.69 (95% CI, 1.40–2.04). In the person-stratified model, the association between elevated hemoglobin concentration and risk of myocardial infarction was attenuated but remained significant.
In this large cohort of Scandinavian blood donors, elevated hemoglobin concentration was associated with an increased risk of vascular events, primarily arterial events. Even though associations were weakened when each person served as their own control, a high hemoglobin concentration may serve as a cardiovascular risk marker.
β-Thalassemia heterozygote state detrimentally affects health expectation
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Thalassemia minor (Tm) individuals, are generally considered healthy. However, the prognosis of Tm individuals has not been extensively studied.
The aim of this study was to evaluate the prognosis of Tm versus controls without β-thalassemia carrier state.
A total of 26,006 individuals seeking thalassemia screening at the AOOR Villa Sofia-V. Cervello, Palermo (Italy) were retrospectively studied. Logistic penalised regression model was used to estimate risk of potential complications and survival techniques were used to study mortality.
We identified a total of 4943 Tm and 21,063 controls. Tm was associated with significantly higher risks of hospitalisation for cirrhosis (OR 1·94, 95% CI 1·30 to 2·90, p = 0·001), kidney disorders (OR 2·11, 95% CI 1·27 to 3·51, p = 0·004), cholelithiatis (OR 1·39, 95% CI 1·08 to 1·79, p = 0·010), and mood disorders (OR 2·08, 95% CI 1·15 to 3·75, p = 0·015). No statistically difference in life expectancy between thalassemia minor and control group was found (HR 1·090, 95% CI 0·777 to 1·555, p < 0·590; log-rank test p = .426).
This study shows that Tm affects the prognosis of Tm carriers regarding health expectation. Probably, iron overload and anaemia for several years may be at the basis of these effects.
Comparison of transradial and transfemoral approaches for percutaneous coronary intervention in patients with acute coronary syndrome and anemia
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Anemia is an independent predictor of bleeding complications and poor clinical outcomes after percutaneous coronary intervention. Percutaneous coronary transradial intervention (TRI) is better than percutaneous coronary transfemoral intervention (TFI) in terms of reducing bleeding complications that can affect the prognosis. This study aims to investigate the clinical outcomes between TRI and TFI for patients with anemia. We analyzed periprocedure complications, in-hospital mortality, and major adverse cardiac events for one year in the Korean TRI registry from January 2013 to April 2014. Patients with chronic kidney disease for whom TFI is preferred were excluded. Anemia was defined as hemoglobin <13 g/dl for men and <12 g/dl for women. A total of 1,279 patients were finally enrolled. Of these, 348 patients had anemia. Among them, 253 patients (72.7%) underwent TRI and 95 patients (27.3%) underwent TFI. There were no significant differences of baseline demographic characteristics between the TRI and TFI groups, except for the incidence of dyslipidemia (TRI 23.7% vs TFI 12.6%, p = 0.023). Multivariate logistic regression analysis revealed lower incidence of composite severe bleeding complications (hazard ratio 0.34, 95% CI 0.12 to 0.99, p = 0.049) and lower incidence of in-hospital mortality than TFI group (hazard ratio 0.74, 95% CI 0.62 to 0.88, p = 0.042). In conclusion, this study suggests that the TRI for patients with anemia may be translated into better prognosis in terms of lower rates of bleeding complications and in-hospital mortality.
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^☆: Reprint requests: Wayne H. Giles, MD, MSc, Cardiovascular Health Branch, CDC/NCCDPHP (MS K-47), 4770 Buford Hwy NE, Atlanta, GA 30341-3717. E-mail: [email protected]

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Outcomes, Health Policy, and Managed CareHematocrit and the risk of coronary heart disease mortality☆

Abstract

Section snippets

Methods

Results

Discussion

J Thorac Cardiovasc Surg

Am Heart J

J Chronic Dis

Am Heart J

Am Heart J

Am J Obstet Gynecol

Hemorheological parameters in coronary artery disease

Clin Hemorheol Microcirc

Whole blood viscosity and haematocrit are associated with internal carotid atherosclerosis in men

Coron Artery Dis

Relation of hematocrit values to coronary heart disease, arterial hypertension, and respiratory impairment in occupational and population groups of the Athens area

Angiology

Blood pressure variations, hemorheological determinants, and platelet aggregation in hypertensive patients with unstable angina

Clin Exp Hypertens

Haematocrit, hypertension and risk of stroke

J Intern Med

Hemorheological study in patients with coronary artery disease

Cardiology

Plasma viscosity, fibrinogen and haematocrit in the course of unstable angina

Eur Heart J

Haematocrit: a predictor of cardiovascular mortality?

J Intern Med

Hematocrit correlates with blood pressure in young male office workers

Ind Health

Smoking is associated with higher cardiovascular risk in young women than in men: the Tecumseh Blood Pressure Study

J Hypertens

Relationship between smoking and cardiovascular risk factors in the development of peripheral arterial disease and coronary artery disease: Edinburgh Artery Study

Eur Heart J

Outcomes, Health Policy, and Managed Care
Hematocrit and the risk of coronary heart disease mortality☆