Tonje A. Aksnes

Increased sympathetic reactivity may predict insulin resistance: an 18-year follow-up study

Insulin resistance and sympathetic activity are related by a positive feedback system. However, which precedes the other still remains unclear. The present study aimed to investigate the predictive role of sympathoadrenal activity in the development of insulin resistance in an 18-year follow-up study. We also examined whether reactivity to 2 different stress tests, a cold pressor test and a mental stress test, would differ in their predictive power. The 2 tests are supposed to represent different reactivity mechanisms: alpha- and beta-adrenergic responses, respectively. At entry, arterial plasma epinephrine and norepinephrine concentrations were measured in 99 healthy men (age, 19.3 +/- 0.4 years, mean +/- SD) during rest, a mental stress test, and a cold pressor test. Fasting plasma glucose concentration was measured at entry and at follow-up. Insulin resistance at follow-up was calculated using the homeostasis model assessment of insulin resistance (HOMA-IR). Eighty subjects (81%) were eligible for follow-up after 18.0 +/- 0.9 years (mean +/- SD). The norepinephrine responses to cold pressor test at entry predicted plasma glucose concentration (r = 0.301, P = .010) and HOMA-IR (r = 0.383, P = .004) at follow-up in univariate analyses. In multiple regression analyses, corrected for fasting glucose at entry, family history of diabetes, blood pressure-lowering medication, body mass index at entry, and level of exercise, norepinephrine response to cold pressor test was found to be a positive predictor of future HOMA-IR (P = .010). This is the first long-term follow-up study in white subjects showing that sympathetic reactivity predicts future insulin resistance 18 years later. These findings may provide further insights into the pathophysiologic mechanisms of insulin resistance.

Impact of New-Onset Diabetes Mellitus on Development of Atrial Fibrillation and Heart Failure in High-Risk Hypertension (from the VALUE Trial)

Hypertension and diabetes mellitus (DM) are known risk factors for atrial fibrillation (AF). We investigated the influence of new-onset DM on developing AF in the VALUE trial population of high-risk hypertensive patients. Five thousand two hundred fifty patients of the 15,245 participants in the VALUE trial had DM at baseline and 1,298 of the initially nondiabetic patients developed DM during the average 4.2-year follow-up. The presence of AF was determined by central analyzed electrocardiograms at baseline and changes were assessed yearly. Patients without AF at baseline and with any AF by later electrocardiograms were defined as patients with new-onset AF. Patients with new-onset and baseline DM were compared with patients without DM by a Cox regression model with adjustment for prespecified covariates. Five hundred fifty-one patients developed new-onset AF during the trial. Patients with new-onset DM had a significantly higher event rate of new-onset AF with a hazard ratio of 1.49 (1.14 to 1.94, p = 0.0031) compared with patients without DM, and there was a trend toward more AF in patients with DM at baseline. Patients with new-onset DM had also more persistent AF (hazard ratio 1.87, 1.28 to 2.74, p = 0.0014). Patients with new-onset DM and AF had a hazard ratio of 3.56 for heart failure (2.86 to 4.44, p <0.0001) compared with patients with new-onset DM without AF. In conclusion, hypertensive patients who developed DM during the VALUE trial had more AF than did patients without DM, and this may explain some of their concomitant high risk of hospitalization for heart failure.

Prevention of new-onset atrial fibrillation and its predictors with angiotensin II-receptor blockers in the treatment of hypertension and heart failure.

Atrial fibrillation is the most frequent occurring sustained cardiac arrhythmia and it is related to common cardiac disease conditions. Hypertension increases the risk of atrial fibrillation by approximately two-fold and, because of the high prevalence of hypertension, it accounts for more cases of atrial fibrillation than any other risk factor. In recent years, there are two large hypertension trials (LIFE and VALUE) and two large heart failure trials (CHARM and Val-HeFT) reporting the beneficial effect of angiotensin II-receptor blockers (ARBs) on new-onset atrial fibrillation, beyond the blood pressure-lowering effect. Blockade of the renin–angiotensin system may prevent left atrial dilatation, atrial fibrosis, dysfunction and conduction velocity slowing. Some studies also indicate direct anti-arrhythmic properties. This review aims to consider the preventive effect of ARBs on new-onset atrial fibrillation observed in recent reports from these trials, and to discuss possible mechanisms of the beneficial effect of angiotensin II-receptor blockade.

Amlodipine and valsartan: calcium channel blockers/angiotensin II receptor blockers combination for hypertension

Despite the availability of numerous antihypertensive agents, many patients with hypertension fail to achieve the blood pressure goals set out in current guidelines. These patients remain at a high risk of cardiovascular morbidity and mortality and require effective treatment options to reduce that risk. Current guidelines recognize that many patients require multiple antihypertensive agents to achieve blood pressure goals. Numerous combination therapies are available, although there is currently no available fixed-dose alternative that combines the benefits of angiotensin receptor blockers and calcium channel blockers. This article explores the rationale for using multiple-mechanism therapy with the angiotensin receptor blocker valsartan and the calcium channel blocker amlodipine and discusses the clinical data supporting this novel approach to the treatment of hypertension.

The effect of antihypertensive agents on new-onset diabetes mellitus: time to amend the guidelines?

Recent large hypertension trials have shown great differences in incidence of new-onset diabetes mellitus among patients receiving different antihypertensive drug therapies. The incidence of diabetes is unchanged or increased by the use of thiazide diuretics and β-adrenoceptor antagonists (β-blockers) and unchanged or decreased by ACE inhibitors, calcium channel blockers (CCBs), and angiotensin II type 1 receptor antagonists (angiotensin receptor blockers). Recent results from ASCOT (Anglo-Scandinavian Cardiac Outcomes Trial) showed superiority of the ‘new’ combination of CCBs and ACE inhibitors over the ‘old’ or ‘conventional’ combination of β-blockers and diuretics. In this review, the results from some of the large hypertension trials are discussed, and the hypotheses on how different antihypertensive drug regimens can affect glucose homeostasis are considered. The question now is whether the results from these recent trials should affect the choice of antihypertensive treatment, particularly for special groups. However, the key goal is still to reduce BP, and this usually requires combinations of drugs.

Clinical Implications of the 2013 ESH/ESC Hypertension Guidelines: Targets, Choice of Therapy, and Blood Pressure Monitoring

The European Society of Hypertension (ESH)/European Society of Cardiology (ESC) 2013 guidelines for the management of arterial hypertension included simplified blood pressure (BP) targets across patient groups, more balanced discussion on monotherapy vs. combination therapy, as well as reconfirmation of the importance of out-of-office BP measurements. In light of these updates, we wished to review some issues raised and take a fresh look at the role of calcium channel blocker (CCB) therapy; an established antihypertensive class that appears to be a favorable choice in many patients. Relaxed BP targets for high-risk hypertensive patients in the 2013 ESH/ESC guidelines were driven by a lack of commanding evidence for an aggressive approach. However, substantial evidence demonstrates cardiovascular benefits from more intensive BP lowering across patient groups. Individualized treatment of high-risk patients may be prudent until more solid evidence is available. Individual patient profiles and preferences and evidence for preferential therapy benefits should be considered when deciding upon the optimal antihypertensive regimen. CCBs appear to be a positive choice for monotherapy, and in combination with other agent classes, and may provide specific benefits beyond BP lowering. Ambulatory and home BP monitoring have an increasing role in defining the diagnosis and prognosis of hypertension (especially non-sustained); however, their value for comprehensive diagnosis and appropriate treatment selection should be more widely acknowledged. In conclusion, further evidence may be required on BP targets in high-risk patients, and optimal treatment selection based upon individual patient profiles and comprehensive diagnosis using out-of-office BP measurements may improve patient management.

High screening blood pressure at young age predicts future masked hypertension: A 17 year follow-up study

Abstract Objective. Approximately 10–20% of the general population have masked hypertension. However, how best to identify affected individuals is uncertain, and what predicts future masked hypertension is largely unknown. This study aimed to identify longitudinal predictors of masked hypertension. Methods. A long-term follow-up study of 100 healthy young men who had normal (n = 28) or high (n = 72) screening blood pressure (BP) at the compulsory military draft was carried out. They were examined in a detailed and highly standardized way for cardiovascular risk markers at baseline and at follow-up after a mean of 17.4 years. Results. At follow-up, 40% had masked hypertension. Participants with high screening BP had a 4.8 times higher likelihood of having masked hypertension at follow-up compared to men with low screening BP (odds ratio 4.8, 95% confidence interval 1.7–13.5, p = 0.003). Furthermore, only 25% of the men with masked hypertension had high normal office BP at follow-up, and the remaining 75% would, according to guidelines, not be recommended ambulatory BP measurements, and thus go undiagnosed. Conclusion. Our data suggest that high screening BP at a young age is an important predictor of future masked hypertension in young men, and that BP measurement according to guidelines is insufficient to uncover masked hypertension.

Treatment of hypertension in diabetes: what is the best therapeutic option?

Patients with diabetes mellitus have a high risk of cardiovascular disease, and the latter is the leading cause of premature mortality in diabetic patients. Treatment of risk factors and comorbidities, such as hypertension, is very important and may effectively prevent cardiovascular events. The blood pressure goal in diabetic patients should be below 140/90 mmHg, probably down to 130–135/85 mmHg, although the evidence for this is scarce. To reach this blood pressure goal, intensive lifestyle intervention and often combinations of different antihypertensive drugs must be initiated. In combination treatment, a blocker of the renin–angiotensin system should be included, and according to the results of the ACCOMPLISH trial, a combination of a renin–angiotensin system blocker and a calcium channel blocker should probably be the first choice.

Predictors of abdominal adipose tissue compartments: 18-year follow-up of young men with and without family history of diabetes.

BACKGROUND Abdominal adipose tissue (AAT) consists of visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT), which can be further divided into superficial and deep SAT. Despite being a key factor in the development of metabolic and cardiovascular diseases, what predicts future amount of AAT is largely unknown. OBJECTIVE To determine long-term predictors of amount of AAT. METHODS This was a mean 18-year follow-up study of a cohort of 94 healthy young Caucasian men, with and without a family history of diabetes (FHD). Cardiovascular risk markers were examined both at baseline and at follow-up. At follow-up, computed tomography (CT) of AAT was conducted to assess amount of superficial and deep SAT, and VAT. RESULTS In multiple regression analyses, baseline body mass index (BMI) remained a positive predictor of future amount of superficial and deep SAT, while high-density lipoprotein (HDL) cholesterol was a negative predictor of all three sub-compartments. Baseline risk markers were generally stronger predictors among men with FHD, than among men without. In addition, FHD had greater impact on amount of deep SAT and VAT, than on amount of superficial SAT. CONCLUSION Our data suggest that the traditional cardiovascular risk markers BMI, HDL cholesterol and family history of diabetes are long-term predictors of the different abdominal adipose tissue compartments from young towards middle age in healthy men. In men with family history of diabetes, cardiovascular risk markers at a young age seem to be of greater importance to future amount of abdominal adipose tissue, than among men without.

Family history of hypertension and serum triglycerides predict future insulin sensitivity: a 17-year follow-up study of young men.

Objective: Low insulin sensitivity is closely related to both cardiovascular diseases and diabetes development. Still, correlates of insulin sensitivity have mainly been examined in cross-sectional studies. As far as we are aware, the longitudinal stability of insulin sensitivity in young men is largely unknown. We aimed for the first time to examine both the stability (tracking) and longitudinal predictors of future insulin sensitivity in healthy young men with and without a family history of diabetes or hypertension. Methods: We performed a 17-year follow-up study of a cohort of 100 healthy young men. Cardiovascular risk markers, including insulin sensitivity measured by the gold standard method – hyperinsulinaemic isoglycaemic glucose clamp – were examined both at baseline and at follow-up. Results: Baseline insulin sensitivity showed no significant correlation with insulin sensitivity at follow-up, whereas all other measured cardiovascular risk markers had significant correlation (tracking coefficients 0.4–0.7). In multiple regression analyses, family history of hypertension and baseline triglycerides remained the negative predictors of future insulin sensitivity. This was driven by the strong correlations in men with family history of diabetes. Conclusion: Our data suggest that clamp-derived insulin sensitivity is not a stable feature in young men, and that family history of hypertension and baseline triglycerides were associated with future insulin sensitivity, especially in men with a family history of diabetes, and irrespective of blood pressure status 17 years earlier. These findings provide further insight into the development of insulin sensitivity and related diseases.