High Blood Pressure in Women Tied to Diabetes Risk

BOSTON, Oct. 10 -- Women with high or rising blood pressure are up to three times more likely to develop type 2 diabetes, researchers here found.

These findings were independent of body mass index, and other components of the metabolic syndrome, including hypercholesterolemia and elevated glucose levels, David Conen, M.D., of Harvard and the Harvard School of Public Health, reported online in the European Heart Journal.

They analyzed observations from a prospective cohort study of 38,172 health professionals in the Women's Health Study. All participants were free of diabetes and cardiovascular disease at the start of the study in 1993. Follow-up continued through March 2004.

Despite the close relationship between the prevalence of hypertension and type 2 diabetes, there had been little information on blood pressure levels and the subsequent development of diabetes, Dr. Conen and colleagues wrote. Data for women were even more limited.

Women were classified into four categories according to self-reported baseline blood pressure (120/75 mm Hg, 120-129/75-84 mm Hg, 130-139/85-89 mm Hg, and self-reported hypertension, at least 140/90 mm Hg, or treatment for the condition).

They were further classified according to progression to a higher blood pressure category during the first 48 months of follow-up.

During the 10.2 years of follow-up, 1,672 women developed type 2 diabetes. Of these in each of the four baseline categories, 1.4, 2.9, 5.7, and 9.4% developed diabetes (P for trend 0.0001).

The overall incidence rate was 4.5 events per 1,000 person-years. In addition, women with baseline hypertension had a seven-fold increased risk of developing diabetes compared with women with optimal blood pressure at the outset.

After adjusting for various factors, such as age, ethnicity, smoking, alcohol intake, BMI, exercise, family history of diabetes, these risk differences were attenuated but still statistically significant.

Multivariable adjusted hazard ratios (HRs) for incident diabetes across the four baseline categories (95% confidence interval) were 0.66 (0.55-0.80), 1.0 (reference group), 1.45 (1.23-1.71), and 2.03 (1.77-2.32) (P for trend 0.0001).

This amounted to an adjusted three-fold increased risk among women with hypertension compared with those having optimal blood pressure, the researchers said.

Stratification by body mass index revealed similar results, the researchers said.

The results were also similar, showing a three-fold increased risk, when women with incident diabetes during the first 48 months were excluded. Rising blood pressure was a significant risk, the researchers said, with a highly significant trend of increasing diabetes across the categories of blood pressure change.

Adjusted hazard ratios for incident diabetes after 48 months showed that those whose blood pressure rose but remained within the normal range had a 26% increased risk compared with women who remained stable or whose blood pressure declined.

On the other hand, women who progressed to hypertension had a 64% increased diabetes risk (P for trend 0.0001), a risk approaching that of those with established hypertension.

Compared with an overall rate of 4.5 events per 1,000 person-years, the rate in the optimal blood pressure category was 1.5 events per 1,000 person-years, meaning that these women had a low risk of developing diabetes, the researchers said.

However, women with high normal blood pressure had a much higher risk, and the risk for those with established hypertension was substantial. After 10 years, almost 10% of these women had diabetes, according to the researchers.

Although the absolute risk was highest among overweight and obese women, a strong association remained for normal-weight women, they said. Also among women with no more than one of three components of the metabolic syndrome, excluding glucose or blood pressure, the same strong trend across the blood pressure categories remained.

Taken together, the researchers said, these finding suggest that obesity and the metabolic syndrome do not explain the entire association between blood pressure and incident diabetes.

A possible mechanism for the findings may be the progression of endothelial dysfunction, the investigators suggested. Several studies have shown that markers of endothelial dysfunction are associated with new-onset diabetes, and that this condition is closely related to blood pressure and hypertension.

Markers of inflammation, such as C-reactive protein, have been consistently related to incident diabetes and to blood pressure levels, suggesting that inflammation might be a factor in the association between blood pressure, the metabolic syndrome, and diabetes.

Study limitations included the use of self-reported blood pressure, although the validity of this approach has been confirmed in other studies of health professionals, the researchers said.

Because the study included mainly Caucasian women, the findings may not apply to other populations, and residual confounding is a concern in all epidemiological studies, they said.

These findings highlight the fact that cardiovascular risk factors are interrelated and occur in clusters, the researchers said.

Clinicians should be aware of these relationships to improve the management of patients at increased risk for cardiovascular disease. None of these risk factors should be looked at individually, Dr. Conen's team said.

This study was supported by grants from the National Heart, Lung and Blood Institute and the National Cancer Institute. Dr. Conen received grants from the Swiss National Science Foundation and the Janggen-Poehn Foundation, St. Gallen, Switzerland.