Drug-nutrient interactions in the elderly

Dietary supplement use has steadily increased among the elderly to improve or maintain overall health and for specific reasons, such as to promote bone or heart health. The use of medicinal products is also high among the elderly, thus increasing the risk for drug–nutrient interactions (DNI). Although, DNI are well recognized, their importance is slowly getting recognition as a potential factor that may affect outcomes in the elderly with multiple comorbidities requiring multiple medications, in the background of declining functional reserves, altered nutritional status, and aging-associated physiological changes that alter the disposition (absorption, distribution, metabolism, or elimination) of the drug or nutrient and its effect on the body. Nearly half of patients using dietary supplements with prescription drugs are at risk of some interaction, with a third considered clinically significant, particularly with drugs with a narrow therapeutic index. These interactions may go undetected as the majority of patients do not disclose their supplement use to healthcare professionals. Increasing recognition of such interaction may help reduce these adverse effects. In this chapter, we will summarize different types of DNI, highlight aging-associated alterations in pharmacokinetics and pharmacodynamics that increase predisposition to DNI, and discuss issues in regulating dietary supplements that can potentially improve their safety

Middle or Older Age at the Time of Bariatric Surgery for Morbid Obesity is Associated with a Higher Risk for Cardiovascular Events

Conclusion: The incidence of CV (cardiovascular) events were higher in older group. Operating earlier, controlling OSA (obstructive sleep apnea) and hypertension may help further reduce CV events in morbidly obese individuals

The risk of adverse cardiovascular outcomes after bariatric surgery in patients with morbid obesity with and without obstructive sleep apnea

Background: Weight loss after bariatric surgery in obese patients reduces adverse cardiovascular (CV) outcomes; however, it is not known if similar benefits are maintained in patients with and without obstructive sleep apnea (OSA). We investigated whether weight loss after laparoscopic adjustable gastric banding (LAGB) results in similar CV event rates in patients with and without OSA. Methods: Differences in LAGB-induced weight loss on CV outcomes (myocardial infarction, heart failure, stroke, atrial fibrillation [AF] and pulmonary embolism) in those with OSA and matched non-OSA patients were determined by Kaplan-Meier and Cox regression analysis and predictors of CV events identified. Results:Out of 828 obese patients [body mass index (BMI) ≥35 kg/m2] who underwent LAGB and were followed for 11 years, OSA was present in 217 (26%).The mean age was 44±11 years, mean BMI 49±8 kg/m2 and median follow-up 63.6 months; the mean reduction in BMI was 10 kg/m2 at 3 years. Patients with no history of OSA had minimal CV events compared to those with OSA (Fig A and B, at 5 years 1% vs 22%, p Conclusions: Patients with OSA, despite weight loss after LABG, continued to have higher CV events, particularly heart failure and AF. Further investigation is warranted into whether compliance with OSA treatment helps reduce CV events

Gender differences in risk of stroke in patients with restless legs syndrome

Background Patients with Restless Legs Syndrome (RLS) have been recently reported to have a higher risk of stroke when compared to non-RLS patients, but the difference appears to be related to the duration of RLS. We hypothesize that diabetes mellitus, a condition that accelerates cardiovascular diseases, may enhance the risk of stroke more in RLS than in non-RLS patients. Methods and Results Patients diagnosed with RLS based on the International Restless Legs Syndrome Study Group criteria from a community-based sleep study center were compared to a 1:2 propensity matched non-RLS group. The association of diabetes and stroke in RLS and non-RLS patients in men and women were performed using Chi-Square and Cochran-Mantel-Haenszel Tests. Results Stroke was diagnosed in 29 out of 385 (7.5%) patients with RLS (mean age 55.1±0.7 years, 45% female) which was significantly higher than 32 out of 770 (4.2%; p=0.02) patients without RLS (mean age 54±0.5 years, 46% females). The presence of diabetes in the RLS group was associated with a 3 fold increased risk of stroke (OR 2.96, 95% Confidence Interval 1.05-8.37, p=0.03) compared to a 1.1 fold increased risk in non-RLS patients (OR: 1.08, 95% CI 0.44-2.65; p=0.87). This was significantly higher in female diabetics with RLS (18.2%) than in male diabetics (7.0%, p=0.03) or nondiabetics (5.7% in females vs 3.9% in males, p=0.52). Predictors of stroke in patients with RLS were the presence of hypertension, diabetes and female sex. Hypertension, diabetes and atrial fibrillation were predictors of stroke in non-RLS patients. Conclusions Gender differences exist in the risk of stroke in RLS patients with a 3.0 fold higher risk of stroke in diabetic women compared to diabetic men. In non-RLS patients, no significant difference in risk of stroke was found between women and men. Mechanisms underlying increased risk of stroke in RLS patients need to be defined and whether better diabetes control help reduce the stroke risk in RLS patients needs to be further investigated

Impact of obstructive sleep apnea severity on cardiac events in patients with normal or prolonged ventricular repolarization

BACKGROUND: Prolonged cardiac repolarization is associated with increased risk of ventricular arrhythmias which are aggravated by several triggering factors including excess catecholamine state and electrolyte abnormalities. We studied the impact of severity of obstructive sleep apnea (OSA) on ventricular tachyarrhythmias and mortality in patients with normal or prolonged ventricular repolarization as this is not well defined. METHODS: 338 patients [59% male, mean age: 61 ± 13] undergoing polysomnography between January 2012 to June 2015 who also had a 12-lead ECG were divided into 4 groups: Group 1-no evidence of OSA, Group 2-mild, Group 3-moderate, Group 4-severe, based on apnea-hypopnea index (AHI) none\u3c5, mild 5-14, moderate 15-29, severe \u3e29 respectively. The differences in prevalence of non-sustained ventricular tachycardia between the 4 groups and incidence of ventricular fibrillation (VF) and overall mortality were determined using Cochran-Armitage Trend and Chi-Square. In addition, differences in VT and VF and overall mortality were determined between the 4 groups and compared to those with normal or prolonged repolarization (defined as JTc interval [JTc=QTc -QRS] \u3e380ms for female and \u3e360ms for male). RESULTS: Out of 338 patients, [51% with preexisting heart failure] the prevalence of VT increased with OSA severity from 44% in Group 1 to 46%, 50%, 67% in Group 2 to 4 [p=0.004] respectively. In patients with normal repolarization, prevalence of VT increased with OSA severity from 33% in Group 1 to 50%, 60% and 84% in Group 2 to 4 [p=0.001]. However, in patients with prolonged repolarization, there was no additional impact of OSA severity on VT in Group 1 to 4: 50%, 45%, 45%, 60% [p=0.094]. The risk of VF or death increased with worsening OSA severity from Groups 1 -4: 2.7%, 5.4%, 5.8%, 9.8%, however this was not significantly significant [p=0.53]. CONCLUSIONS: In patients with underlying cardiac disease, the prevalence of VT increases with OSA severity mainly in patients with normal repolarization but have minimum effect on patients with prolonged repolarization. There is a trend toward higher risk of VF or death with worsening sleep apnea that needs to be confirmed in a larger population

Risk of atrial fibrillation and stroke after bariatric surgery in patients with morbid obesity with or without obstructive sleep apnea

Background and purpose: Weight loss in morbidly obese patients reduces atrial fibrillation (AF); however, it is unknown whether similar benefits are maintained in patients with obstructive sleep apnea (OSA). We sought to determine whether incident AF and stroke rates are affected by OSA after weight loss and to identify predictors of AF and stroke. Methods: Differences in laparoscopic adjustable gastric banding-induced weight loss on incident AF and stroke events in those with and without OSA in the entire and in propensity-matched cohorts were determined longitudinally, and independent predictors of AF and stroke were identified. Results: Of 827 morbidly obese patients who underwent laparoscopic adjustable gastric banding (mean age, 44±11 years; mean body mass index, 49±8 kg/m2), incident AF was documented in 4.96% and stroke in 5.44% of patients during a mean 6.0±3.2-year follow-up. Despite a similar reduction in body weight (19.6% and 21% in 3 years), new-onset AF was significantly higher in patients with OSA than without OSA in the entire (1.7% versus 0.5% per year; P\u3c0.001) and propensity-matched cohorts. Incident stroke was higher in the OSA than in the non-OSA group (2.10% versus 0.47% per year; P\u3c0.001), but only 20% of patients with stroke had documented AF. On multivariate analysis, OSA (hazard ratio, 2.88 [95% CI, 1.45–5.73]), age, and hypertension were independent predictors of new-onset AF, and OSA (hazard ratio, 5.84 [95% CI, 3.02–11.30]), depression, and body mass index were for stroke events. Conclusions: In morbidly obese patients who underwent laparoscopic adjustable gastric banding, despite similar weight loss, patients with OSA had a higher incidence of AF and stroke than patients without OSA. Both non-AF and AF-related factors were involved in increasing stroke risk. Further investigation is warranted into whether OSA treatment helps reduce AF or stroke events in this population

The beneficial effect of weight reduction on adverse cardiovascular outcomes following bariatric surgery is attenuated in patients with obstructive sleep apnea

Weight loss after bariatric surgery is associated with reduction in adverse cardiovascular outcomes; however, the impact of obstructive sleep apnea (OSA) on reduction of cardiovascular outcomes after bariatric surgery in morbidly obese patients is not known. We retrospectively assessed differences in cardiovascular events after laparoscopic adjustable gastric banding (LAGB)-induced weight loss in patients with and without OSA before and after propensity score matching for age, sex, body mass index (BMI), and major comorbidities between the two groups and determined predictors of poor outcomes. OSA was present in 222 out of 830 patients (27%) who underwent LAGB between 2001 to 2011. Despite a similar reduction in BMI (20.0% and 20.8%), a significantly higher percentage of cardiovascular events were observed in patients with than without OSA (35.6% vs 6.9%;

The risk of adverse coronary events is higher in patients with severe obstructive sleep apnea following percutaneous coronary intervention

BACKGROUND: Limited data is available on the impact of obstructive sleep apnea (OSA) or continuous positive airway pressure (CPAP) therapy on coronary events or mortality in patients undergoing percutaneous coronary intervention (PCI). METHODS: From a multispecialty community sleep center, patients undergoing polysomnography (PSG) from 2011 to 2014 were identified. Of these, those who had PCI performed after PSG were included in this analysis. Coronary events (myocardial infarction or redo PCI), mortality or composite endpoint (MI, redo PCI and death) after PCI was compared between those with severe OSA (apnea-hypopnea index [AHI] 330) or non-severe OSA (AHI\u3c30) using Wilcoxon, Chi square test, and Kaplan-Meier analysis. Predictors of composite and individual end points were determined using proportional hazard cox model. RESULTS: The cohort consisted of 222 patients (mean age 63.2±11.3 years, 70% male) of whom 39% had severe OSA, 24% moderate OSA, 28 mild OSA and 9% had no OSA. The composite endpoint after PCI was significantly higher in those with severe OSA, compared to those with non-severe OSA (36% vs 24%, hazard ratio: 1.8, 95% CI: 1.1-2.9; p-value: 0.02, Fig). Multivariate analysis showed severity of OSA, MI and age\u3e65 as independent predictors for composite endpoints. (Fig) CONCLUSIONS: Severe OSA has a negative impact on coronary event rate after PCI. Whether treating OSA with CPAP therapy helps reduce these events needs to be further investigated

P6223 Restless legs syndrome is an independent risk factor for heart failure with preserved ejection fraction

Background: Restless legs syndrome (RLS), a poorly recognised sleep disorder, has been recently associated with atrial fibrillation and ventricular hypertrophy but its association with heart failure with preserved ejection fraction (HFpEF) is not known. Methods: RLS patients fulfilling International Restless Legs Syndrome Study Group criteria were identified from a large community-based sleep center and those without history of heart failure (HF) and with preserved left ventricular ejection fraction (LVEF) (≥50%) were propensity-matched (age, sex, hypertension, hyperlipidemia, diabetes, prior myocardial infarction (MI), atrial fibrillation) to non-RLS patients. Development of new onset HFpEF in the two groups, and predictors of HFpEF were determined using Cox Proportional hazard model. Results: A total of 432 patients with RLS who had a baseline echocardiogram with preserved LVEF between 2012–2015 were identified and 1:1 propensity-matched to non-RLS patients with preserved LVEF (mean age 56±13.7 years, 62% female). Over a mean follow-up of 18±8 months, new onset heart failure developed in 63 (14.6%) patients with RLS compared to 37 (8.6%) in non-RLS group (OR 1.9, 95% CI 1.2–2.9; p=0.004). Only 5% of patients with new onset HF had reduced LVEF (mean 33.7%±10.8%), while 95% had LVEF ≥50% (mean 62.8% ± 0.7% p\u3c0.001). RLS (OR 2.16, 95% CI 1.36–3.42; p=0.001), prior MI (OR 3.89, 95% CI 1.38–10.95; p=0.01), hypertension (OR 3.66, 95% CI 1.25–10.76; p=0.02), diabetes mellitus (OR 2.75, 95% CI 1.64–4.59; p\u3c0.01), and age (OR 1.05, 95% CI 1.02–1.07; p\u3c0.001) were independent predictors of HFpEF. Conclusion: Independent of prior MI, hypertension, diabetes and age, the presence of RLS was associated with the development of HFpEF, suggesting this to be an unrecognized risk factor for HF. Further investigation confirming this association, mechanisms and whether control of RLS reduces the development of HFpEF are warranted

P4416 Racial differences in weight loss and its impact on cardiovascular outcomes after bariatric surgery in patients with morbid obesity

Background: Weight loss after bariatric surgery in morbidly obese patients reduces adverse cardiovascular (CV) outcomes; but racial differences in the effectiveness of weight loss and its impact on CV outcomes are not defined. Purpose: To determine differences in laparoscopic adjustable gastric banding (LAGB)-induced weight loss and its impact on long-term CV events (myocardial infarction, heart failure [HF], atrial fibrillation [AF], stroke, and pulmonary embolism] in morbidly obese white and black patients. Method: Patients with morbid obesity (body mass index [BMI] ≥40 kg/m2 or 35 kg/m2 with obesity-related comorbidity) who underwent LAGB between 2001–2011 at a single institution with long-term follow-up were included. Differences in weight loss after LAGB in white and black patients and its impact on CV events were determined by Kaplan-Meier analysis, and predictors for CV outcomes were identified using Cox regression analysis. Results: Of 760 obese patients who underwent LAGB, 173 (23%) were black and 587 (77%) white. After 1:1 propensity matching for age, BMI, hypertension, dyslipidemia, and diabetes mellitus, 212 patients (106 in each group, with mean age 44±10 years, mean BMI 48±8kg/m2) were followed for CV events. Over a mean follow-up of 5.8±3.0 years, both groups had significant weight loss from baseline with a reduction in BMI of 21.5% (from 51 to 40 kg/m2) in the white patient group and 19.2% (from 48.2 to 39.0 kg/m2) in the black patient group, which was not significantly different between the groups (p=0.60). Despite similar reduction in BMI after LAGB, the cumulative CV events were significantly higher in the black patients than the white patients (log-rank p=0.03, Fig A), mainly due to a higher incidence of HF (7.5% vs 1.9%, p=0.05) and AF (6.6% vs 1.9%, p=0.05) in black patients (Fig B). Black race was an independent predictor of CV events [hazard ratio (HR): 2.60, 95% CI: 1.18–5.69, p\u3c0.017], while sex, BMI, hypertension, and diabetes were not. View largeDownload slide Conclusion: Although no difference in weight loss and its maintenance after LAGB is seen between black and white patients, the likelihood of adverse CV events in the black population is higher due to a higher incidence of new onset HF and AF. Further investigation into mechanisms underlying higher predisposition to HF and AF in black patients after bariatric surgery is warranted