Chlorthalidone and Insulin Resistance (page 319)
Chlorthalidone, a thiazide-like diuretic considered to be superior to other diuretics in the treatment of hypertension, is well known to increase risk of diabetes mellitus in hypertensive patients. Although hypokalemia is thought to play an important role in this effect, previous studies have indicated that there is a component of thiazide diuretic-induced dysglycemia that is independent of serum potassium (K). In the study by Raheja et al in this issue of Hypertension, chlorthalidone was shown to trigger increased sympathetic nerve activity and to induce insulin resistance despite K supplementation to maintain the serum K constant. Interestingly, the metabolic adverse effects of chlorthalidone were prevented by concomitant administration of the mineralocorticoid receptor antagonist spironolactone but not by the angiotensin receptor blocker irbesartan in the same hypertensive patients. The study not only suggested that K supplementation to prevent hypokalemia alone is not sufficient to prevent chlorthalidone-induced insulin resistance but also demonstrated a major role of aldosterone in mediating sympathetic activation and metabolic adverse effects of thiazides. Because elevated plasma glucose and sympathetic overactivity contribute to the poor prognosis of patients with cardiovascular disease, the addition of spironolactone might maximize the long-term cardiovascular benefit of chlorthalidone therapy in hypertensive patients by reducing the adverse metabolic consequences and neurohormonal activation of thiazide diuretics (Figure 2, top left panel of Raheja et al).
Pulse Pressure and Risk of Atrial Fibrillation (page 347)
Atrial fibrillation is the most prevalent sustained cardiac arrhythmia, and the prevalence is increasing. Atrial fibrillation is associated with a marked increased risk of ischemic stroke and cardiovascular mortality, and, because hypertension is a major risk factor for atrial fibrillation, prevention by blood pressure–lowering treatment is increasingly important. Increased pulse pressure with increased pulsatile load on the heart is a marker of arterial stiffness and typical for hypertension in the more advanced stages. The relationship of new-onset atrial fibrillation detected on annual ECGs with blood pressure variables was examined in 8810 participants in the Lifestyle Interventions and Independence for Elders Study, a study of hypertensive patients older than 55 years with ECG determined left ventricular hypertrophy. Baseline and in-treatment pulse pressure and baseline and in-treatment systolic blood pressure predicted new-onset atrial fibrillation, independent of baseline age, sex, race, body build, Framingham risk score, treatment allocation, and in-treatment heart rate and Cornell product. Pulse pressure was the strongest single blood pressure predictor of new-onset atrial fibrillation in comparison with systolic blood pressure, diastolic blood pressure, and mean arterial pressure. Thus, when evaluating the risk of atrial fibrillation in hypertensive patients with ECG-determined left ventricular hypertrophy, both baseline pulse pressure and pulse pressure during antihypertensive treatment should be considered. Furthermore, lowering of pulse pressure may be a target to prevent new-onset atrial fibrillation in hypertensive patients.
Maternal Cardiac Function in Fetal Growth-Restricted Pregnancies (page 437)
Preeclampsia, a pregnancy complication of placental etiology, is associated with maternal global diastolic dysfunction and increased risk for the development of maternal cardiovascular disease several years later. This prospective study tested the hypothesis that women with other pregnancy complications of placental etiology, namely fetal growth restriction, would also exhibit global diastolic dysfunction. Fetal growth-restricted pregnancies were associated with left ventricular diastolic dysfunction in a third and impaired myocardial relaxation in two thirds of women (Figure of Raheja et al). However, unlike in preeclampsia, cardiac geometry and intrinsic myocardial contractility were preserved in fetal growth–restricted pregnancy.
The finding of widespread impaired left ventricular diastolic function in women who have had fetal growth-restricted pregnancies may explain their increased long-term cardiovascular morbidity. Recent studies of women whose pregnancies were complicated by preeclampsia have shown persistence of left ventricular moderate-severe asymptomatic abnormal function and geometry ≤2 years after delivery in a significant proportion of women. These findings predispose the latter women to a much higher risk of hypertension, heart failure, and cardiac death, all of which may be ameliorated by appropriately timed therapeutic interventions. The natural history of asymptomatic diastolic dysfunction in women whose pregnancies were affected by fetal growth restriction is unknown, and follow-up studies are needed to assess the latter, as well as the role of interventions, in preventing cardiovascular morbidity in these women.
- © 2012 American Heart Association, Inc.