Low medication adherence may explain part of the high prevalence of apparent treatment resistant hypertension (aTRH). We assessed medication adherence and aTRH among 4,026 participants taking ≥ 3 classes of antihypertensive medication in the population-based REGARDS Study using the 4-item Morisky Medication Adherence Scale (MMAS). Low adherence was defined as a MMAS score ≥ 2. Overall, 66% of participants taking ≥ 3 classes of antihypertensive medication had aTRH. Perfect adherence on the MMAS was reported by 67.8% and 70.9% of participants with and without aTRH, respectively. Low adherence was present among 8.1% of participants with aTRH and 5.0% of those without aTRH (p<0.001). Among those with aTRH, female gender, residence outside the US stroke belt or stroke buckle, physical inactivity, elevated depressive symptoms, and a history of coronary heart disease were associated with low adherence. In the current study, a small percentage of participants with aTRH had low adherence.
Hypertension; Treatment Resistant Hypertension; Medication adherence; Risk Factors
Accumulating evidence suggests that increased visit-to-visit variability (VVV) of blood pressure is associated with stroke. No study has examined the association between VVV of blood pressure and stroke in postmenopausal women, and scarce data exists as to whether this relation is independent of the temporal trend of blood pressure. We examined the association of VVV of blood pressure with stroke in 58,228 postmenopausal women enrolled in the Women's Health Initiative. Duplicate blood pressure readings, which were averaged, were taken at baseline and at each annual visit. VVV was defined as the standard deviation about the participant's mean systolic blood pressure (SBP) across visits (SD), and about the participant's regression line with SBP regressed across visits (SDreg). Over a median follow-up of 5.4 years, 997 strokes occurred. In an adjusted model including mean SBP over time, the hazard ratios (95% CI) of stroke for higher quartiles of SD of SBP compared to the lowest quartile (referent) were 1.39 (1.03-1.89) for quartile 2, 1.52 (1.13-2.03) for quartile 3, and 1.72 (1.28-2.32) for quartile 4 (P trend<0.001). The relation was similar for SDreg of SBP quartiles in a model that additionally adjusted for the temporal trend in SBP (P trend<0.001). The associations did not differ by stroke type (ischemic vs. hemorrhagic). There was a significant interaction between mean SBP and SDreg on stroke with the strongest association seen below 120 mmHg. In postmenopausal women, greater VVV of SBP was associated with increased risk of stroke, particularly in the lowest range of mean SBP.
hypertension; blood pressure; stroke; postmenopause; women
Nighttime blood pressure (BP) dipping can be quantified as the ratio of mean nighttime (sleep) BP to mean daytime (awake) BP. People whose dipping ratio is 0.90 have been referred to as nondippers, and nondipping is associated with cardiovascular disease events. We examined the relationship between systolic nighttime BP dipping in young adults and presence of coronary artery calcium (CAC) 10-15 years later using data from the ambulatory BP monitoring substudy of the Coronary Artery Risk Development in Young Adults (CARDIA) study. Among 239 participants with adequate measures of both nighttime and daytime readings and coronary artery calcium, the systolic BP dipping ratio ranged from 0.72 to 1.24 (mean 0.88, SD 0.06), and CAC was present 10 to 15 years later in 54 participants (22.6%). Compared to those whose systolic BP dipping ratio ranged from 0.88 to 0.92 (Quartile 3), the 57 participants (23.9%) with less pronounced or absent dipping (ratio 0.92 to 1.24, Quartile 4) had an unadjusted odds ratio of 4.08 (95% CI 1.48-11.2) for presence of CAC. The 60 participants (25.1%) with a more pronounced dipping (ratio 0.72 to 0.85, Quartile 1) also had greater odds for presence of CAC (OR 4.76; 95% CI 1.76-12.9). When modeled as a continuous predictor, a U-shaped relationship between systolic BP dipping ratio and future CAC was apparent, and persisted after adjustment for multiple potential confounders (p<0.001 for quadratic term). Both failure of systolic BP to dip sufficiently and “overdipping” during nighttime may be associated with future subclinical coronary atherosclerosis.
ambulatory blood pressure; diurnal blood pressure; blood pressure dipping; coronary artery calcium; subclinical atherosclerosis
Masked hypertension (MHT) and prehypertension (PHT) are both associated with an increase in cardiovascular disease (CVD) risk, relative to sustained normotension. This study examined the diagnostic overlap between MHT and PHT, and their interrelationships with left ventricular (LV) mass index (LVMI), a marker of cardiovascular end-organ damage.
A research nurse performed three manual clinic blood pressure (CBP) measurements on three occasions over a 3-week period (total of nine readings, which were averaged) in 813 participants without treated hypertension from the Masked Hypertension Study, an ongoing worksite-based, population study. Twenty-four-hour ambulatory blood pressure (ABP) was assessed by using a SpaceLabs 90207 monitor. LVMI was determined by echocardiography in 784 (96.4%) participants.
Of the 813 participants, 769 (94.6%) had normal CBP levels (<140/90 mm Hg). One hundred and seventeen (15.2%) participants with normal CBP had MHT (normal CBP and mean awake ABP ≥135/85 mm Hg) and 287 (37.3%) had PHT (mean CBP 120–139/80–89 mm Hg). 83.8% of MHT participants had PHT and 34.1% of PHT participants had MHT. MHT was infrequent (3.9%) when CBP was optimal (<120/80 mm Hg). After adjusting for age, gender, body mass index (BMI), race/ethnicity, history of high cholesterol, history of diabetes, current smoking, family history of hypertension, and physical activity, compared with optimal CBP with MHT participants, LVMI was significantly greater in PHT without MHT participants and in PHT with MHT participants.
In this community sample, there was substantial diagnostic overlap between MHT and PHT. The diagnosis of MHT using an ABP monitor may not be warranted for individuals with optimal CBP.
ambulatory blood pressure monitoring; blood pressure; echocardiography; hypertension
Although research has consistently established that depression and elevated depressive symptoms are associated with an increased risk of acute coronary syndrome (ACS) recurrence and mortality, clinical trials have failed to show that conventional depression interventions offset this risk. As depression is a complex and heterogeneous syndrome, we believe that using simpler, or intermediary, phenotypes rather than one complex phenotype may allow better identification of those at particular risk of ACS recurrence and mortality and may contribute to the development of specific depression treatments that would improve medical outcomes. Although there are many possible intermediary phenotypes, specifiers, and dimensions of depression, we will focus on only two when considering the relation between depression and risk of ACS recurrence and mortality: Inflammation-Induced Incident Depression and Anhedonic Depression. Future research on intermediary phenotypes of depression is needed to clarify which are associated with the greatest risk for ACS recurrence and mortality and which, if any, are benign. Theoretical advances in depression phenotyping may also help elucidate the behavioral and biological mechanisms underlying the increased risk of ACS among patients with specific depression phenotypes. Finally, tests of depression interventions may be guided by this new theoretical approach.
cardiovascular diseases; depressive disorder; depression; acute coronary syndrome; myocardial infarction; phenotype
emotional stress; atherosclerosis; inflammation; endothelin-1
On the surface electrocardiogram (ECG), an abnormally wide QRS|T angle reflects changes in regional action potential duration profiles and in direction of repolarization sequence which is thought to increase the risk of ventricular arrhythmia. We investigated the relationship between abnormal QRS|T angle and mortality in a nationally representative sample of individuals without clinically evident heart disease. We studied 7,052 participants ≥ 40 years of age in the Third National Health and Nutrition Examination Survey (NHANES III) with 12-lead ECGs. Individuals with self-report or ECG evidence of a prior myocardial infarction, QRS duration ≥120 msec, or history of heart failure were excluded. Borderline and abnormal spatial QRS|T angle were defined according to sex-specific 75th and 95th percentiles of frequency distributions. All-cause (n=1093 women, n=1191 men) and cardiovascular mortality (n=462 women, n=455 men) over 14 years was assessed through linkage with the National Death Index. In multivariable analyses, abnormal spatial QRS|T angle was associated with an increased hazard ratio (HR) for cardiovascular mortality in women (HR 1.82, 95% CI 1.05-3.14) and men (HR 2.21, 95% CI 1.32-3.68). An abnormal QRS|T angle was also associated with increased multivariable adjusted HRs for all-cause mortality in women (HR 1.30, 95% CI 0.95-1.78) and men (HR 1.87, 95% CI 1.29-2.7). Borderline QRS|T angle was not associated with increased risk for all-cause or cardiovascular mortality. In conclusion, abnormal QRS|T angle, as measured on a 12-lead ECG, was associated with increased risk for cardiovascular and all-cause mortality in this population-based sample without known heart disease.
electrocardiogram; cardiac mortality; QRS|T angle; epidemiology
Few data are available on factors associated with low adherence or early clopidogrel discontinuation following percutaneous coronary intervention (PCI). Patients (n=284) were evaluated prior to hospital discharge following PCI to identify factors associated with low adherence to clopidogrel 30 days later. Pre-PCI adherence to daily medications was assessed using the 8-item Morisky Medication Adherence Scale (MMAS-8) and categorized as low, medium, or high (scores <6, 6 to <8 and 8, respectively). Low adherence to clopidogrel was defined as a MMAS-8 score < 6 (n=21) or having discontinued clopidogrel (n=11), both ascertained during a 30-day post-PCI interview. At 30 days post-PCI, 11% of patients had low adherence to clopidogrel. The odds ratios (95% confidence interval) for low adherence to clopidogrel was 3.78 (1.09 – 13.1), 3.06 (1.36 – 6.87), 2.46 (0.97 – 6.27) and 3.36 (0.99 – 11.4) for patients who reported, prior to PCI, taking smaller doses of medication due to cost, had difficulty filling prescriptions, had difficulty reaching their primary physician and were not comfortable asking their doctor for instructions, respectively. The odds ratios (95% CI) for low clopidogrel adherence following PCI among patients with medium and low, versus high adherence, to daily medications prior to PCI was 6.13 (1.34 – 28.2) and 10.9 (2.46 – 48.7), respectively. The c-statistic associated with pre-PCI MMAS-8 scores for discriminating low clopidogrel adherence at 30 days post-PCI was 0.733 (95% CI: 0.650 – 0.852). Pre-PCI adherence to daily medications may be a useful indicator for identifying patients who will have low clopidogrel adherence following PCI.
Clopidgrel; medication adherence; percutaneous coronary intervention
Approximately 15% of patients with acute coronary syndromes (ACS) develop posttraumatic stress disorder (PTSD) due to their ACS event. We assessed whether ACS-induced PTSD symptoms increase risk for major adverse cardiac events (MACE) and all-cause mortality (ACM) in an observational cohort study of 247 patients (aged 25–93 years; 45% women) hospitalized for an ACS at one of 3 academic medical centers in New York and Connecticut between November 2003 and June 2005. Within 1 week of admission, patient demographics, Global Registry of Acute Coronary Events risk score, Charlson comorbidity index, left ventricular ejection fraction, and depression status were obtained. At 1-month follow-up, ACS-induced PTSD symptoms were assessed with the Impact of Events Scale-Revised. The primary endpoint was combined MACE (hospitalization for myocardial infarction, unstable angina or urgent/emergency coronary revascularization procedures) and ACM, which were actively surveyed for 42 months after index event. Thirty-six (15%) patients had elevated intrusion symptoms, 32 (13%) elevated avoidance symptoms, and 21 (9%) elevated hyperarousal symptoms. Study physicians adjudicated 21 MACEs and 15 deaths during the follow-up period. In unadjusted Cox proportional hazards regression analyses, and analyses adjusted for sex, age, clinical characteristics and depression, high intrusion symptoms were associated with the primary endpoint (adjusted hazard ratio, 3.38; 95% confidence interval, 1.27 – 9.02; p= .015). Avoidance and hyperarousal symptoms were not associated with the primary endpoint. The presence of intrusion symptoms is a strong and independent predictor of elevated risk for MACE and ACM, and should be considered in the risk stratification of ACS patients.
posttraumatic stress disorder; psychosocial factors; risk factors; acute coronary syndrome; recurrence; behavioral medicine
Premature shortening of leukocyte telomere length has been proposed as a novel mechanism by which depression may confer increased risk of adverse cardiovascular events. Prior studies demonstrating associations of depression and depressive symptoms with shorter leukocyte telomere length were small, included selected psychiatric outpatients, were based on convenience samples, and/or adjusted for a limited number of possible confounding factors.
Methods and Findings
We examined the associations of depressive symptoms, probable depressive disorder, and specific depressive symptom clusters, as assessed by the Center for Epidemiological Studies—Depression (CES-D) scale, with leukocyte telomere length, measured by using a real-time PCR method, in 2,225 apparently healthy participants from the 1995 Nova Scotia Health Survey population-based study. The mean age was 48.2±18.9 years; 49.9% of participants were female; and the mean CES-D score was 7.4±7.9. The mean telomere length was 5,301±587 base pairs. In an unadjusted model, depressive symptoms were significantly associated with longer leukocyte telomere length (B = 27.6 base pairs per standard deviation increase in CES-D, 95% confidence interval [CI] = 3.1–52.1, p = 0.027). This association was no longer significant after adjustment for age and sex (B = 9.5, 95% CI = −14.6–33.6, p = 0.44) or after further adjustment for body mass index, Framingham risk score and previous history of ischemic heart disease (all p's≥0.37). Neither probable depressive disorder nor specific depressive symptom clusters were independently associated with leukocyte telomere length.
Concurrent depressive symptoms were not associated with leukocyte telomere length in a large, representative, population-based study.
To examine the relation between hostility and incident ischemic heart disease (IHD) and to determine whether observed hostility is superior to patient-reported hostility for the prediction of IHD in a large, prospective observational study.
Some studies have found that hostile patients have an increased risk of incident IHD. However, no studies have compared methods of hostility assessment, nor considered important psychosocial and cardiovascular risk factors as confounders. Further, it is unknown whether all expressions of hostility carry equal risk, or whether certain manifestations are more cardiotoxic.
We assessed the independent relationship between baseline observed hostility and 10-year incident IHD in 1,749 adults of the population-based Canadian Nova Scotia Health Survey.
There were 149 (8.5%) incident IHD events (140 non-fatal, 9 fatal) during the 15,295 person-years of observation (9.74 events/1000 person-years). Participants with any observed hostility had a greater risk of incident IHD than those without (p=0.02); no such relation was found for patient-reported hostility. After adjusting for cardiovascular (age, sex, Framingham Risk Score) and psychosocial (depression, positive affect, patient-reported hostility, and anger) risk factors, those with any observed hostility had a significantly greater risk of incident IHD (HR 2.06, 95% CI 1.04–4.08, P=0.04).
The presence of any observed hostility at baseline was associated with a two-fold increased risk of incident IHD over 10 years of follow-up. Compared to patient-reported measures, observed hostility is a superior predictor of IHD.
Observed hostility; patient-reported hostility; ischemic heart disease; depression; positive affect
Pulmonary arterial hypertension (PAH) is a progressive disease which causes exercise limitation, heart failure, and death. We aimed to determine the safety and efficacy of aspirin and simvastatin in PAH.
Methods and Results
We performed a randomized, double-blind, placebo-controlled 2 × 2 factorial clinical trial of aspirin and simvastatin in patients with PAH receiving background therapy at four centers. A total of 92 patients with PAH were to be randomized to aspirin 81 mg or matching placebo and simvastatin 40 mg or matching placebo. The primary outcome was six-minute walk distance (6MWD) at six months. Sixty-five subjects were randomized when the trial was terminated by the DSMB after an interim analysis showed futility in reaching the primary end point for simvastatin. After adjustment for baseline 6MWD, there was no significant difference in the 6MWD at six months between aspirin (n = 32) and placebo (n = 33) [placebo-corrected difference = −0.5 m (95%CI, −28.4 – 27.4 m), p = 0.97] or between simvastatin (n = 32) and placebo (n = 33) [placebo-corrected difference = −27.6 m (95%CI, −59.6 – 4.3 m), p = 0.09]. There tended to be more major bleeding episodes with aspirin compared to placebo (4 events vs. 1 event, respectively, p = 0.17).
Neither aspirin nor simvastatin had a significant effect on the 6MWD, although patients randomized to simvastatin tended to have a lower 6MWD at six months. These results do not support the routine treatment of patients with PAH with these medications.
pulmonary hypertension; clinical trial; anti-platelet agents; endothelial dysfunction
Previous theoretical models predict that elevated inflammation may predict later depressive symptoms, but bidirectional associations are possible. We examined whether depressive symptoms or inflammation predict change in the other over a 3-month period in a sample of post-acute coronary syndrome (ACS) adults.
During hospitalization for their index ACS event (baseline), and then again 1 and 3 months later, 163 post-ACS patients completed the Beck Depression Inventory, a measure of depressive symptom severity with cognitive-affective and somatic-affective subscales. C-reactive protein (CRP) was also assessed at each visit; known correlates of depression and CRP were assessed at baseline. Path analyses were conducted to evaluate prospective associations among depressive symptoms and log-transformed CRP values and whether strength and/or directionality varied by specific depressive symptom dimensions.
Baseline total depressive symptom severity predicted a smaller decrease in CRP from baseline to 1 month (unstandardized parameter estimates (B) = .04; p < .001) controlling for all covariates, as did baseline cognitive-affective depressive symptom severity (B = .10; p = .02). Baseline somatic-affective depressive symptom severity did not predict change in CRP (B = −.002; p = .94). CRP did not predict 1- or 3-month change in total, cognitive-affective, or somatic-affective depressive symptom severity. Results did not differ for men and women.
Greater cognitive-affective and total depressive symptom severity at the time of a cardiac event predicts a smaller decrease in CRP 1 month later, but there was no evidence in this study that CRP predicts change in depressive symptoms.
depression; inflammation; acute coronary syndrome; depressive symptoms; risk factors; cardiovascular disease
Posttraumatic stress disorder (PTSD) is related to acute coronary syndrome (ACS; i.e., myocardial infarction or unstable angina) recurrence and poor post-ACS adherence to medical advice. Since risk perceptions are a primary motivator of adherence behaviors, we assessed the relationship of probable PTSD to ACS risk perceptions in hospitalized ACS patients (n = 420). Participants completed a brief PTSD screen 3–7 days post-ACS, and rated their 1-year ACS recurrence risk relative to other men or women their age. Most participants exhibited optimistic bias (mean recurrence risk estimate between “average” and “below average”). Further, participants who screened positive for current PTSD (n = 15) showed significantly greater optimistic bias than those who screened negative (p < 0.05), after adjustment for demographics, ACS severity, medical comorbidities, depression, and self-confidence in their ability to control their heart disease. Clinicians should be aware that psychosocial factors, and PTSD in particular, may be associated with poor adherence to medical advice due to exaggerated optimistic bias in recurrence risk perceptions.
PTSD; cardiovascular disease; acute coronary syndrome; myocardial infarction; risk perceptions; secondary prevention
vitamin D; ischemic heart disease; cardiovascular disease; Nova Scotia Health Survey
Increased left ventricular (LV) mass and changes in LV geometry may precede hypertension onset. The authors examined the associations of LV mass and geometry, assessed by cardiac magnetic resonance imaging, with hypertension incidence in 2,567 normotensive participants enrolled in 2000–2002 in the Multi-Ethnic Study of Atherosclerosis, an ethnically diverse, population-based, US study. Over a median follow-up of 4.8 years, 745 (29%) participants developed hypertension. In a fully adjusted model including baseline blood pressure, the relative risks of incident hypertension from the lowest to highest LV mass quartile were 1.00 (referent), 1.13 (95% confidence interval (CI): 0.89, 1.43), 1.28 (95% CI: 1.00, 1.63), and 1.78 (95% CI: 1.38, 2.30) (P < 0.001 for linear trend). Higher levels of LV concentric geometry, defined by higher LV mass to end-diastolic volume quartiles, were associated with higher risk of incident hypertension in a fully adjusted model (P = 0.044 for linear trend). In a final model containing both quartiles of LV mass and LV mass/volume along with all covariates including baseline blood pressure, higher LV mass quartiles were associated with incident hypertension (P < 0.001 for linear trend), whereas higher LV mass/volume quartiles were not (P = 0.643 for linear trend). In this multiethnic cohort, alterations in LV mass preceded hypertension onset among normotensive individuals.
hypertension; hypertrophy, left ventricular; magnetic resonance imaging; risk factors
Polypills which include multiple medications for reducing cardiovascular disease (CVD) risk in a single pill have been proposed for population-wide use. The number of US adults eligible for polypills and potential benefits are unknown.
The National Health and Nutrition Examination Survey 2003-2004 and 2007-2008 were analyzed to estimate treatment rates for medications proposed for inclusion in polypills (aspirin, statin, an ACE-inhibitor, and a thiazide-type diuretic for those without, a beta-blocker for those with, a history of myocardial infarction) among US adults. The number of coronary heart disease (CHD) and stroke events potentially prevented through polypill use was projected by published meta-analyses and three large population-based cohort studies. Two polypill eligibility criteria were analyzed (1) US adults ≥ 55 years and (2) US adults with a history of CVD.
There are 67.6 million US adults ≥ 55 years and 15.4 million US adults with a history of CVD and, thus, eligible for polypills using the two outlined criteria. In 2007-2008, 37.3% of US adults ≥ 55 years and 57.0% of those with a history of CVD were taking statins. Use of other polypill medications was also low. Polypill use by US adults age ≥ 55 years is projected to potentially prevent 3.2 million CHD events and 1.7 million strokes over 10 years. Amongst those with a history of CVD, the potential to prevent of 0.9 million CHD events and 0.5 million strokes is projected.
Polypills have the potential to lower CVD incidence substantially among US adults.
Pulmonary arterial hypertension (PAH) is a progressive disease which causes exercise limitation, heart failure, and death. Aspirin and simvastatin are highly effective and safe therapies for other cardiovascular diseases characterized by platelet activation and endothelial dysfunction, but have not been formally studied in PAH.
ASA-STAT is a Phase II, randomized, double-blind, placebo-controlled 2 × 2 factorial clinical trial of aspirin and simvastatin in patients with PAH. A total of 92 subjects were to be randomized to aspirin or aspirin placebo and simvastatin or simvastatin placebo. The primary outcome is the distance walked in six minutes at six months after randomization. Secondary measures include brachial artery flow-mediated dilation, circulating biomarkers of platelet and endothelial function, functional class, quality-of-life, and time to clinical end points. The incidence of adverse events will be compared between treatment groups.
Screening and Enrollment
We screened a total of 712 individuals with PAH. Sixty-five subjects were enrolled when the trial was terminated for futility in reaching the primary end point for simvastatin.
This study aims to determine whether aspirin or simvastatin have beneficial biologic or clinical effects in patients with PAH. The safety and side effects of these commonly prescribed cardiovascular drugs will also be assessed.
Pulmonary hypertension; Endothelial dysfunction; platelets; Clinical trial
We examined the association between blood pressure (BP) reactivity to an anger provocation interview and 10-year incident CVD events in 1,470 adults from the population-based 1995 Nova Scotia Health Survey (NSHS95). In an unadjusted model, those in the highest decile of systolic BP reactivity were more than twice as likely to have an incident CVD event compared to those in the decile with no reactivity (HR = 2.33, 95% CI = 1.15 – 4.69, P = 0.02). However, after adjusting for age and sex, and then also for Framingham risk score, body mass index, and education, this relationship was attenuated and not statistically significant. Diastolic BP reactivity was not associated with CVD incidence in any model. Individual differences in BP reactivity to a laboratory-induced, structured anger provocation interview may not play a major role in clinical CVD endpoints.
Nondippers (people whose sleep systolic blood pressure (SBP) fails to decrease >10% from daytime SBP) have increased risk of cardiovascular disease. The prevalence of nondipping in younger adults has not been well-studied, nor has its value for predicting hypertension. We examined the prevalence of nondipping in a sub-study of the Coronary Artery Risk Development in Young Adults (CARDIA) Study. We used Cox regression to estimate the hazard ratio (HR) conferred by nondipping for incident prehypertension or hypertension (preHTN/HTN) over 15 years. Of the 264 non-hypertensive participants at baseline, 118 (45%) were nondippers. Blacks were more likely than Whites to be nondippers (52% vs 33%, p=0.004). The incidence rate of preHTN/HTN was 29.2/1000 person-years among dippers and 36.2/1000 person-years among nondippers. Compared to those in the lowest quartile of nighttime to daytime SBP, those in the highest quartile were more likely to develop preHTN/HTN (HR 1.61; p =0.06), but this relationship was attenuated after adjustment (HR 1.34; p =0.27). Our results demonstrate that nondipping is common in young, nonhypertensive adults, and is more common in Blacks than Whites. Nondipping might predate a meaningful clinically detected increase in BP in some people, but more research in larger study samples is needed.
diurnal blood pressure; blood pressure dipping; hypertension
Increased delay to hospital presentation with acute coronary syndrome (ACS) is associated with poor outcomes. While demographic factors associated with this delay have been well described, scarce data are available on the role of modifiable factors, such as psychosocial disorders, on pre-hospital delay. Patients with symptoms of post-traumatic stress disorder (PTSD) often avoid stressful situations and may delay presenting for care when they experience cardiac symptoms. It is unknown, however, whether PTSD symptoms negatively impact the time to presentation during an ACS.
We assessed the relationship between PTSD symptoms and pre-hospital delay in 241 adults with an ACS in the ongoing Prescription Use, Lifestyle, Stress Evaluation (PULSE) study.
Overall, 66% of patients were male; 40% were Hispanic or Latino. The mean age was 61.9±11.6 years old. PTSD symptoms were present in 17.8% of patients. Pre-hospital delay was longer for patients with PTSD symptoms compared to those without [geometric mean: 25.8 hours (95% CI 13.8 – 44.8) vs. 10.7 hours (95% CI 8.3 – 13.8)]; P = 0.005. After multivariable adjustment for age, sex, ethnicity, depression, left ventricular ejection fraction and history of myocardial infarction, the mean pre-hospital delay was 173% (95% CI: 36% –450%) longer for patients with versus without PTSD symptoms.
Among patients presenting with an ACS, PTSD symptoms were independently associated with longer pre-hospital delays. Future studies of pre-hospital delay should examine the mechanisms underlying this association.
The purpose of this study was to assess the association between antidepressant use and incident coronary heart disease (CHD) events in a sample of individuals without known baseline heart disease.
PARTICIPANTS AND METHODS
We studied a group of 970 randomly-selected community-dwelling adults in the 1995 Nova Scotia Health Survey, who were followed for up to ten years. Antidepressant usage was classified according to class. Primary outcomes were acute coronary syndrome hospitalizations or cardiac death, determined by centralized, standardized ratings.
During a follow-up period of ten years, there were 147 incident CHD events (139 acute coronary syndromes and 8 cardiac deaths) during the 8,129 person-years of observation (incidence rate = 18.1 events/1000 person years). In a model controlling for age, sex, Framingham risk score, time to last annual exam, aspirin exposure, and depressive symptoms, an increased risk of CHD events was associated with tricyclic antidepressant exposure (adjusted hazard ratio, 2.10; 95% confidence interval, 1.09–4.06; p=0.027).
In this prospective population-based study, exposure to tricyclic antidepressants was associated with higher risk of first CHD events.
While depression is clearly associated with increased mortality after acute myocardial infarction, there is a paucity of data examining the impact of depression on patients with unstable angina (UA). We analyzed the relationship between depressive symptoms and all-cause mortality (ACM) among patients with UA who were enrolled in a prospective multi-center study of depression and acute coronary syndrome (ACS). Depressive symptoms were measured with the Beck Depression Inventory (BDI) within 1 week of the ACS event, and patients were selected for BDI score 0 to 4, or ≥10. Our sample included 209 UA patients, with 104 (50%) having BDI score ≥10. Proportional hazards analyses adjusted for variables including left ventricular ejection fraction, GRACE risk score, and Charlson comorbidity index. In multivariable analyses, BDI score ≥10 was associated with increased risk of 42-month ACM (HR=2.04, 95% CI 1.20–3.46, p=0.008) compared with BDI score 0 to 4. In conclusion, our results confirm and extend prior evidence linking depression to worse outcomes in UA, and suggest that interventions that address depression may be worth examining across the spectrum of risk in ACS.
depression; acute coronary syndrome
Persistent elevation of inflammatory markers such as C-reactive protein (CRP) is associated with increased risk of recurrent cardiac events after acute coronary syndromes (ACS). There is conflicting evidence as to whether aspirin can reduce CRP after ACS. We investigated whether dosage and adherence to aspirin was associated with CRP 3 months after ACS. Adherence to aspirin was monitored using an electronic chip stored in a pill bottle cap for 3 months in a cohort of 105 patients enrolled within one week of an ACS. CRP was measured at baseline and 3 months. Logistic regression was used to test whether poor adherence to aspirin and lower aspirin dosage were associated with increased CRP levels, controlling for age, ACS type, disease comorbidity, baseline CRP, use of clopidogrel and statins, depressive symptoms, smoking, and adherence to other medications. Aspirin adherence was inversely correlated with CRP at 3 months (Spearman’s r = −0.36, p<.001). In the adjusted model, every 10% decrease in aspirin adherence was associated with 1.7 (95% CI 1.2–2.4) increased odds of CRP ≥3.0mg/l at 3 months; and low-dose aspirin was associated with 7.1 (95%CI 1.5 – 33.3) increased odds of CRP ≥3.0mg/l. Charlson comorbidity index, depressive symptoms, and baseline CRP were also predictive of CRP ≥3.0mg/l at 3 months. The association between aspirin adherence and CRP was not attenuated by controlling for other risk reducing behaviors. In conclusion, there is a strong association between aspirin adherence and CRP post-ACS.
aspirin; C-reactive protein; inflammation; acute coronary syndrome