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Prediabetes Plus Hypertension Equals Coronary Artery Disease

May 19, 2018

High blood pressure and prediabetes together may do more harm to the body than either one alone.

A combination of prediabetes plus hypertension increases the risk for cardiovascular disease (CVD) more than either risk factor alone, according to new research published on April 18 in Hypertension.


The worldwide epidemic of obesity and physical inactivity are said to be the main reasons for the increase of prediabetes, while atherosclerotic cardiovascular disease is said to be the primary cause for mortality hyperglycemia. In stable, new-onset coronary artery disease, hypertension increased coronary severity and clinical prognosis despite no significant difference between prediabetes and normal glucose regulation groups.

This is the first study of its type looking into the association between slightly elevated blood sugar levels and high blood pressure. Researchers found that prediabetes didn’t increase cardiovascular risk by itself. But when they looked at prediabetes paired with high blood pressure, they found a significant increase in coronary artery disease severity and cardiovascular events.

One of the most important treatments to pay attention to is hypertension for those with prediabetes. Although thiazides may increase insulin resistance, dyslipidemia, and accelerate conversion to overt DM, in the large ALLHAT study, with metabolic syndrome, chlorthalidone lowered high blood pressure and was unsurpassed in reducing arthero-sclerotic-cardiovascular-disease (ASCVD) and renal outcomes compared with lisinopril, amlodipine, or doxazosin. Even though ASCVD with DM vs normoglycemia is two to three times higher, controlling high blood pressure is the most important target with prediabetes.

A total of 7,121 consecutive patients with angina-like chest pain who received coronary angiography were evaluated and 4,193 patients with angiography-proven stable, new-onset coronary artery disease were enrolled into the study. They were divided into three groups according to diabetes mellitus status and further stratified by hypertension.  The purpose was to see if prediabetes alone or combined with hypertension is an independent risk factor for cardiovascular disease. This study aimed to further confirm whether the relation of prediabetes to cardiovascular disease differs between individuals with or without hypertension. All subjects were regularly followed up for the occurrence of the possible end points.

Comparisons of coronary artery disease severity and outcomes were performed among these groups. During an average of 11,338 patient-years of follow-up, 434 (10.35%) cardiovascular events occurred. No significant difference was observed in coronary severity and composite end point events between prediabetes and normal glucose regulation groups. However, when hypertension was also included as a stratifying factor, cardiovascular disease risk, assessed by coronary severity and clinical prognosis, was significantly elevated in the prediabetes-plus-hypertension and diabetes-plus-hypertension groups compared with the reference group with normal glucose regulation and normal blood pressure. The present study indicated that among patients with stable, new-onset coronary artery disease, the increased cardiovascular risk with prediabetes is largely driven by the coexistence of hypertension rather than just prediabetes.

About half of all Americans have hypertension and more than a third have prediabetes. (Ninety percent of them don’t even know it, according to the Centers for Disease Control and Prevention.)

The researchers followed up at six-month intervals to track all-cause death, nonfatal myocardial infarction, stroke, unplanned revascularization and hospitalized unstable angina. They compared the instances, severity and outcomes of coronary artery disease among the groups.

Among the subjects, 43 percent were defined as prediabetes, approximately 36 percent were defined as DM and approximately 22 percent were defined with normal glucose. During an average of more than 11,300 patient-years of follow-up, the researchers found 434, or 10.4 percent, cardiovascular events occurred.

After adjusting for age, sex, and other factors, the association between prediabetes mellitus and CVD was not observed. When hypertension was incorporated in stratifying factors, adjusted CVD risk was elevated significantly (odds ratio, 2.41; 95% confidence interval, 1.25-4.64) in the prediabetes-and-hypertension combined group, and coexistence of diabetes mellitus and hypertension made CVD risk significantly increased, reaching 3.43-fold higher than the reference group. Blood glucose levels within prediabetic range is significantly associated with elevated risks for diabetes mellitus after multivariable adjustment, but only when it is concurrent with other disorders, such as hypertension, will it significantly increase CVD risk.

“Although this is a relatively short-term study, longer-term follow-up of this population will lead to better understanding of the effects of pre-DM alone or plus hypertension on CVD outcomes,” the authors concluded.  Moreover, a prospective randomized control trial with a large sample size and long-term follow-up is urgently needed to further confirm these findings.

Practice Pearls:

  • The results show that CAD severity in people with prediabetes is primarily associated with the coexistence of hypertension.
  • Clinicians and public health officials must encourage therapeutic lifestyles with prediabetes, but treating hypertension is also absolutely required to address ASCVD risk.
  • The presence of comorbid hypertension was an independent predictor of worsening CAD severity and special attention should be paid to patients with both issues.

Hypertension. 2018;HYPERTENSIONAHA.118.11063  Originally published April 18, 2018