Association of Post-Traumatic Stress Disorder Symptoms Following Hurricane Katrina With Incident Cardiovascular Disease Events Among Older Adults With Hypertension.

OBJECTIVE: To determine the association of post-traumatic stress disorder (PTSD) symptoms following Hurricane Katrina with incident cardiovascular disease (CVD) events in older, hypertensive, community-dwelling adults both overall and stratified by age, sex, and race. METHODS: This was a prospective cohort study performed in Southeastern Louisiana 12-24 months following Hurricane Katrina through February 2011. Participants were community-dwelling older adults (n = 2,073) enrolled in the Cohort Study of Medication Adherence Among Older Adults with no known history of CVD events. PTSD symptoms were assessed via telephone interview 12-24 months following Hurricane Katrina using the PTSD CheckList-Specific Version. The presence of PTSD symptoms was defined by scores greater than or equal to 37. Incident CVD events (stroke, myocardial infarction, hospitalization for congestive heart failure, or CVD death) were identified and adjudicated over a median 3.8-year follow-up period. RESULTS: Overall, 8.6% of participants screened positive for PTSD symptoms, and 11.6% had an incident CVD event during follow-up. PTSD symptoms were associated with an adjusted hazard ratio (aHR) for CVD events of 1.7 (95% confidence interval [CI], 1.1, 2.6). The association was present among blacks (aHR, 3.3, 95% CI, 1.7, 6.3) but not whites (aHR, 0.9, 95% CI, 0.4, 1.9); the interaction of PTSD symptoms and race on CVD events was statistically significant. CONCLUSION: PTSD symptoms following Hurricane Katrina were associated with a higher risk of incident CVD in older adults with hypertension, with a stronger association in blacks compared with whites.

Sodium, blood pressure, and cardiovascular disease: further evidence supporting the American Heart Association sodium reduction recommendations.

Recent reports of selected observational studies and a meta-analysis have stirred controversy and have become the impetus for calls to abandon recommendations for reduced sodium intake by the US general population. A detailed review of these studies documents substantial methodological concerns that limit the usefulness of these studies in setting, much less reversing, dietary recommendations. Indeed, the evidence base supporting recommendations for reduced sodium intake in the general population remains robust and persuasive. The American Heart Association is committed to improving the health of all Americans through implementation of national goals for health promotion and disease prevention, including its recommendation to reduce dietary sodium intake to <1500 mg/d.

Salt consumption and cardiovascular, renal, and hypertensive diseases: clinical and mechanistic aspects.

PURPOSE OF REVIEW: This review will discuss some relevant and novel studies on the relationship between sodium intake and cardiovascular structure and function, focusing on blood pressure independent effects of salt on the heart, arteries, and kidneys. RECENT FINDINGS: Several new reports clearly demonstrate the role of high dietary salt in mediating cardiovascular and renal morbidity and mortality including stroke, myocardial infarction, arterial stiffening, heart failure, and renal insufficiency. A number of recent studies also indicate that in addition to increased sodium intake, simultaneous decrease in potassium intake may aggravate adverse cardiovascular and renal manifestations. SUMMARY: It is now generally accepted that there is a direct positive correlation between dietary salt and arterial pressure. Thus, the beneficial effects of dietary salt reduction are, at least in part, due to a decrease in arterial pressure. Furthermore, the beneficial, pressure-independent effects of sodium restriction on the heart, blood vessels, and kidneys are being increasingly recognized, but not generally appreciated.

Pressure overload.

This review discusses cardiac consequences of pressure overload. In response to elevated pressure, the ventricular hypertrophy compensates for the increased wall stress. However, the ventricular hypertrophy involves numerous structural adaptations that may lead to ventricular dysfunction and, eventually, heart failure. Particular emphasis is placed on molecular mechanisms that govern the development of hypertrophy and that may lead to maladaptive structural changes resulting in adverse cardiac events.

Novel concepts in the genesis of hypertension: role of LOX-1.

Hypertension is a common disease and a potent risk factor for cardiovascular disease. Tremendous strides have been made in understanding its genesis in the last 2 decades. Hypertension is often clustered with other cardiovascular risk factors, such as dyslipidemia and diabetes. The state of hypertension is often associated with increased vascular oxidative stress. Oxidative stress promotes proliferation and hypertrophy of vascular smooth muscle cell and collagen deposition, leading to thickening of the vascular media and narrowing of the vascular lumen. Oxidative stress also injures endothelium, impairs endothelium-dependent vascular relaxation and increases vascular contractile activity. Further, oxidative stress also oxidizes LDL-cholesterol. It has been shown that oxidized low-density lipoprotein (ox-LDL) activates renin-angiotensin system (RAS) and angiotensin II via its type 1 receptor activates ox-LDL receptor LOX-1. This mutually facilitative cross-talk between ox-LDL and RAS may be an important component in the development of hypertension. Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is a receptor for ox-LDL. This review summarizes the role of LOX-1 in the pathogenesis of hypertension.

Cardiovascular effects of inhibition of renin-angiotensin-aldosterone system components in hypertensive rats given salt excess.

This study examined the role of the renin-angiotensin-aldosterone system (RAAS) in mediating cardiovascular and renal damage in spontaneously hypertensive rats (SHR) given salt excess. Since the circulating RAAS is inhibited in this model, it permits examination of the role of local tissue RAASs in mediating this injury. To this end, male 8-wk SHR were divided into 7 groups. The control group (C) received normal NaCl (0.6%) diet. All other groups were given 8% NaCl chow. In addition, group 2 was given placebo, group 3 the mineralocorticoid receptor blocker eplerenone (100 mg.kg(-1).day(-1)), group 4 the angiotensin converting enzyme inhibitor quinapril (3 mg.kg(-1).day(-1)), group 5 the angiotensin II type 1 receptor blocker candesartan (10 mg.kg(-1).day(-1)), and groups 6 and 7 eplerenone and either quinapril or candesartan. The treatments lasted 8 wk. Compared with controls, mean arterial pressure (MAP), renal blood flow, coronary flow reserve, minimal coronary vascular resistance, diastolic time constant, and maximal rate of ventricular pressure fall were all adversely affected by salt loading. Left ventricular mass and fibrosis as well as proteinuria were also markedly increased by salt overload. Eplerenone induced only slight changes, whereas quinapril and candesartan normalized all indexes except MAP. Combination therapy also normalized all indexes, including MAP. These data suggest that 1) cardiovascular and renal damage induced by salt excess in the SHR were not pressure dependent; 2) mineralocorticoids were only marginally involved in this model; and 3) local tissue generation of angiotensin II may be, at least in part, responsible for the other adverse effects.

Association of depression with antihypertensive medication adherence in older adults: cross-sectional and longitudinal findings from CoSMO.

BACKGROUND: Little is known about the associations between depressive symptoms, social support and antihypertensive medication adherence in older adults. PURPOSE: We evaluated the cross-sectional and longitudinal associations between depressive symptoms, social support and antihypertensive medication adherence in a large cohort of older adults. METHODS: A cohort of 2,180 older adults with hypertension was administered questionnaires, which included the Center for Epidemiologic Studies-Depression Scale, the Medical Outcomes Study Social Support Index, and the hypertension-specific Morisky Medication Adherence Scale at baseline and 1 year later. RESULTS: Overall, 14.1% of participants had low medication adherence, 13.0% had depressive symptoms, and 33.9% had low social support. After multivariable adjustment, the odds ratios that participants with depressive symptoms and low social support would have low medication adherence were 1.96 (95% confidence interval (CI) 1.43, 2.70) and 1.27 (95% CI 0.98, 1.65), respectively, at baseline and 1.87 (95% CI 1.32, 2.66) and 1.30 (95% CI 0.98, 1.72), respectively, at 1 year follow-up. CONCLUSION: Depressive symptoms may be an important modifiable barrier to antihypertensive medication adherence in older adults.

Angiotensin II, mechanotransduction, and pulsatile arterial hemodynamics in hypertension.

The aortic blood pressure curve involves two components: a steady component, the mean arterial pressure (MAP), which is dependent on cardiac output and vascular resistance, and a pulsatile component pulse pressure (PP), which is dependent on arterial stiffness and pulse wave reflections. The transduction mechanisms of MAP and PP differ markedly, involving focal adhesion kinase for MAP and oxygen free radicals for PP. Angiotensin II (ANG II) and its blockade are associated with changed vascular resistance and MAP; however, their effects on PP (peripheral and mostly central PP) have been inadequately investigated. In hypertensive rats, when compared with their normotensive controls, ANG II blockade normalizes central PP (<50 mmHg) but not MAP when the same drug dosage is used for each. In hypertensive patients, ANG II blockade reduces arterial stiffness and pulse wave reflections, but with the same reduction in MAP, there is a greater reduction in central than peripheral PP, thereby increasing carotid-brachial PP amplification. With long-term ANG II blockade, the hypertensive arteriolar hypertrophy observed at baseline is corrected in association with reduced arteriolar reflection coefficients, reduced carotid arterial attachments linking alpha(5)-integrin to its ligand fibronectin, and decreased circulating C-reactive protein. When given a normal salt diet, each of these factors contributes separately in reducing arterial stiffness and wave reflections. These responses disappear with a high-salt diet, a condition that usually involves the activation of the local vascular renin-angiotensin-aldosterone system and can be prevented by its selective blockade. Thus ANG II inhibition seems to contribute independently in reducing central PP and aortic stiffness.

Angiotensin blockade prevents salt-induced injury of the renal circulation in spontaneously hypertensive rats.

BACKGROUND/AIMS: We hypothesized that renal damage induced by salt overload may be related to increased activity of the renin-angiotensin system. Thus, we examined the renal effects of angiotensin II receptor blockade in spontaneously hypertensive rats (SHR) with salt overload. Two different blockers were used to demonstrate that the effect depends on receptor blockade per se. METHODS: Male, 8-week-old SHR were divided into 4 groups; the control group was given regular chow, the remaining 3 groups were given chow with 8% salt. In addition, the third group was given candesartan (10 mg/kg/day) and the fourth losartan (30 mg/kg/day). Treatment lasted for 8 weeks. RESULTS: Compared with controls, mean arterial pressure increased in salt-loaded rats and was not decreased by candesartan or losartan. Indices of renal function including renal blood flow, glomerular filtration rate, and urinary protein excretion were greatly and adversely affected by salt overload, and they were completely restored with either drug. CONCLUSION: These results demonstrated that dietary salt excess adversely affected renal function, hemodynamics and structure. Angiotensin receptor blockade did not affect arterial pressure but prevented other adverse effects of salt overload, indicating that renal damage was not dependent on arterial pressure but, more likely, on another mechanism involving the renin-angiotensin system.

A hybrid 4-item Krousel-Wood Medication Adherence Scale predicts cardiovascular events in older hypertensive adults.

BACKGROUND: There is a need for a brief, open access, self-report medication adherence scale that overcomes challenges of existing adherence tools, is associated with incident cardiovascular disease (CVD), and identifies low 'implementation' adherers to antihypertensive medications to facilitate blood pressure management. METHODS AND RESULTS: Antihypertensive medication adherence was assessed in a cohort of 1532 older hypertensive adults without prior CVD using the self-report 4-item Krousel-Wood Medication Adherence Scale (K-Wood-MAS-4), a hybrid tool developed to predict pharmacy refill and which captures four domains of adherence behavior: self-efficacy, physical function, intentional medication-taking, and forgetfulness. The 4-item scale categorized participants as low and high adherers using scores at least 1 and less than 1, respectively. Participants were followed after K-Wood-MAS-4 assessment to identify incident CVD events (stroke, myocardial infarction, congestive heart failure, or CVD death). The prevalence of low adherence was 38.7%. During a median follow-up of 2.8 years (maximum 3.8 years), 136 (8.9%) participants had an incident CVD event; 12.8 and 6.4% in low and high adherers, respectively. The adjusted hazard ratio (aHR) for incident CVD associated with low versus high adherence was 2.29 [95% confidence interval (CI): 1.61, 3.26]. Results were similar when stratified by age [<75 years - aHR 3.53 (95% CI: 1.65, 7.56); ≥75 years - aHR 1.98 (95% CI: 1.32, 2.97)], sex [women - aHR 1.90 (95% CI: 1.16, 3.12); men - aHR 2.80 (95% CI: 1.68, 4.65)], and race [black - aHR 2.22 (95% CI: 0.93, 5.31); white - aHR 2.26 (95% CI: 1.54, 3.34)]. CONCLUSION: Low medication adherence using the 'hybrid' K-Wood-MAS-4 predicts incident CVD in a cohort of older adults with established hypertension.

Mechanisms underlying obesity associated with systemic and renal hemodynamics in essential hypertension.

Obesity and hypertension frequently coexist and are considered major "factors of risk" associated with coronary heart disease. This report identifies the systemic and renal hemodynamic alterations associated with obesity in normotensive and essential hypertensive patients. An expanded intravascular (plasma) volume is associated with obesity, which is related to an increased venous return to the heart, increased cardiac output, and increased blood flow to kidneys and other organs in normal and hypertensive patients. The cardiac consequences result in structural and functional alterations. Although recently postulated pathophysiologic mechanisms have been associated with obesity, none has yet been related to the hemodynamic alterations associated with obesity that coexist in patients with essential hypertension.

Partial adherence to antihypertensive therapy fails to achieve full cardiovascular benefits in hypertensive rats.

BACKGROUND: Partial adherence to antihypertensive therapy remains a public health challenge and may be associated with increased cardiovascular risk. We quantitatively evaluated cardiovascular risk inherent in partial therapy adherence in spontaneously hypertensive rats with accelerated hypertension. METHODS: Adult spontaneously hypertensive rats were divided into 5 groups; Group 1 (controls) did not receive any treatment, whereas all other rats (Groups 2-5) were given nitric oxide synthase inhibitor N-nitro-l-arginine methyl ester (L-NAME) to exacerbate hypertension. Group 2 (untreated/nonadherers) was given L-NAME but not antihypertensive medication; Group 3 (Perfect Adherers) was treated daily with candesartan (10 mg/kg); Group 4 was given candesartan 3 times a week, whereas Group 5 received candesartan only during the last 6 days of the 3-week experiment (Partial Adherers). At the end, indices of systemic and regional (kidneys, brain, and heart) hemodynamics, and indices of left ventricular function were determined. RESULTS: Treatment with L-NAME aggravated hypertension, adversely affected target organ blood flows and resistances, and grossly impaired ventricular function. Perfect adherence with candesartan completely reversed the adverse cardiovascular effects of L-NAME intervention. In partial adherers (Groups 4 and 5), arterial pressure decreased and reached control values. However, target organ hemodynamics and heart function showed only slight improvements, if any. CONCLUSIONS: The results demonstrate that partial adherence to therapy reduces arterial pressure, but may not prevent target organ damage. If replicated in humans, these results may have important clinical implications in hypertensive patients.

Medication adherence in older clinic patients with hypertension after Hurricane Katrina: implications for clinical practice and disaster management.

BACKGROUND: In post-disaster situations, additional barriers may reduce antihypertensive medication adherence. METHODS: Between November 2005 and August 2006, 210 hypertensive patients receiving care at a multispecialty group practice in New Orleans completed a structured questionnaire. Antihypertensive medication adherence was measured with the Hill-Bone medication compliance subscale. In a subset of patients, data on difficulties patients encountered with blood pressure medications in the aftermath of Hurricane Katrina were collected. RESULTS: : Seventy-six percent of patients reported damage to their residence and 46% of patients had less-than-perfect medication adherence. After multivariate adjustment, less than perfect medication adherence postdisaster was more common among people aged <65 years (prevalence ratio = 1.37; 95% confidence interval: 1.03-1.82) and non-whites (1.32; 95% confidence interval: 1.02-1.71). Uncontrolled blood pressure (systolic/diastolic > or =140/> or =90 mm Hg) was more common in those with less-than-perfect adherence than their counterparts with perfect adherence (51% versus 42%, respectively). In addition, 7% of patients reported not bringing their blood pressure medications when they evacuated, 28% ran out of blood pressure medications, 16% reported difficulties getting medications filled, and 28% reported a blood pressure medication change postdisaster. CONCLUSIONS: Opportunities exist to improve disaster planning and prescription refill processes and increase medication adherence and hypertension control postdisasters.

Optimal treatment of hypertension with diastolic heart failure.

Approximately 5 million people in the United States have heart failure. Epidemiologic studies have demonstrated that at least one half of patients who have clinically overt heart failure have diastolic heart failure (DHF), or heart failure with preserved ejection fraction. DHF is characterized by concentric remodeling with normal left ventricular end-diastolic volume, abnormalities of active relaxation, and increased passive ventricular stiffness. Diuretics are an essential component of therapy for most patients who have DHF, and treatment of hypertension is a cornerstone of therapy designed to prevent or to treat DHF. Several antihypertensive agents have been shown to effectively reduce wave reflection, including angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, calcium antagonists, and nitrates. Lifestyle changes may also be helpful.

Risk Factors for Low Pharmacy Refill Adherence Among Older Hypertensive Men and Women by Race.

BACKGROUND: Sex-race stratification may lead to identification of risk factors for low antihypertensive medication adherence that are not apparent when assessing risk factors in women and men without race stratification. We examined risk factors associated with low pharmacy refill adherence across sex-race subgroups (white women, black women, white men, black men) within the Cohort Study of Medication Adherence among Older Adults (n = 2,122). METHODS: Pharmacy refill adherence was calculated as proportion of days covered using all antihypertensive prescriptions filled in the year prior to a baseline risk factor survey. Sex- and sex-race-stratified multivariable Poisson regression models with robust standard errors were used to estimate adjusted prevalence ratios and 95% confidence intervals for associations between participant characteristics and low adherence. RESULTS: Prevalence of low adherence was 22.9% vs. 40.7% in white vs. black women (P < 0.001) and 26.3% vs. 37.2% in white vs. black men (P = 0.003). In multivariable models, reducing antihypertensive medication due to cost was associated with low adherence within each sex-race subgroup. Additional factors associated with low adherence included shorter hypertension duration and comorbidities in white women; not being married and depressive symptoms in white men; and ≥6 primary care visits/year and complementary and alternative medicine use in black men. Among men, not being married and reporting depressive symptoms were associated with low adherence for whites, but not blacks. CONCLUSIONS: Identification of sex-race-specific risk factors for low antihypertensive medication adherence may guide development and implementation of tailored interventions to increase antihypertensive medication adherence and blood pressure control among older patients.

Analogy of cardiac and renal complications in essential hypertension and aged SHR or L-NAME/SHR.

Hypertension plays major causative roles in development of cardiac failure and end-stage renal disease (ESRD). Cardiac and renal involvements in hypertension and relevant pharmacological interventions have been extensively studied in our laboratories. Our findings demonstrated that aged spontaneous hypertensive rats (SHR) developed reduced coronary flow reserve, increased coronary vascular resistance and cardiac fibrosis, and impaired cardiac function. Moreover, aged SHR naturally developed glomerular hypertension and ischemia, proteinuria, and glomerular sclerosis and interstitial fibrosis. These naturally-occurring cardiac and renal involvements in aged SHR are very similar to these target organ changes in essential hypertension. Furthermore, we have been able to reproduce similar derangements in younger adult SHR by nitric oxide synthesis inhibition. These changes are identical to the pathophysiological alterations in heart and kidney found in old SHR as well as clinically. Antihypertensive therapeutic interventions provided cardiac and renal protection and, perhaps even prevention in the aged SHR and younger adult SHR with suppressed nitric oxide synthesis. Recent clinical trails have translated these pathophysiological observations demonstrating that angiotensin II inhibition affords remarkable cardiac and renal benefits to patients with essential hypertension. Thus, both the aged SHR as well as younger adult SHR with suppressed nitric oxide synthesis very closely mimic the cardiac and renal outcomes seen in patients with essential hypertension. They accordingly have become extremely useful experimental models of hypertensive heart disease and ESRD seen with severe nephrosclerosis. The latter hypertensive rat model with induced endothelial dysfunction is recommended enthusiastically for its foregoing as well as time-saving and economic values.