Exploring Overlaps Between the Genomic and Environmental Determinants of LVH and Stroke: A Multicenter Study in West Africa.
ABSTRACT: BACKGROUND:Whether left ventricular hypertrophy (LVH) is determined by similar genomic and environmental risk factors with stroke, or is simply an intermediate stroke marker, is unknown. OBJECTIVES:We present a research plan and preliminary findings to explore the overlap in the genomic and environmental determinants of LVH and stroke among Africans participating in the SIREN (Stroke Investigative Research and Education Network) study. METHODS:SIREN is a transnational, multicenter study involving acute stroke patients and age-, ethnicity-, and sex-matched control subjects recruited from 9 sites in Ghana and Nigeria. Genomic and environmental risk factors and other relevant phenotypes for stroke and LVH are being collected and compared using standard techniques. RESULTS:This preliminary analysis included only 725 stroke patients (mean age 59.1 ± 13.2 years; 54.3% male). Fifty-five percent of the stroke subjects had LVH with greater proportion among women (51.6% vs. 48.4%; p < 0.001). Those with LVH were younger (57.9 ± 12.8 vs. 60.6 ± 13.4; p = 0.006) and had higher mean systolic and diastolic blood pressure (167.1/99.5 mm Hg vs 151.7/90.6 mm Hg; p < 0.001). Uncontrolled blood pressure at presentation was prevalent in subjects with LVH (76.2% vs. 57.7%; p < 0.001). Significant independent predictors of LVH were age <45 years (adjusted odds ratio [AOR]: 1.91; 95% confidence interval [CI]: 1.14 to 3.19), female sex (AOR: 2.01; 95% CI: 1.44 to 2.81), and diastolic blood pressure > 90 mm Hg (AOR: 2.10; 95% CI: 1.39 to 3.19; p < 0.001). CONCLUSIONS:The prevalence of LVH was high among stroke patients especially the younger ones, suggesting a genetic component to LVH. Hypertension was a major modifiable risk factor for stroke as well as LVH. It is envisaged that the SIREN project will elucidate polygenic overlap (if present) between LVH and stroke among Africans, thereby defining the role of LVH as a putative intermediate cardiovascular phenotype and therapeutic target to inform interventions to reduce stroke risk in populations of African ancestry.
Project description:Electrocardiographic (ECG) left ventricular hypertrophy (LVH) is a strong predictor of cardiovascular (CV) morbidity and mortality. However, the predictive value of ECG LVH in treated hypertensive patients remains unclear.A total of 33,357 patients (aged ? 55 years) with hypertension and at least 1 other coronary heart disease (CHD) risk factor were randomized to chlorthalidone, amlodipine, or lisinopril. The outcome of the present study was all-cause mortality; and secondary endpoints were CHD, nonfatal myocardial infarction (MI), stroke, angina, heart failure (HF), and peripheral arterial disease. Cornell voltage criteria (S in V3 + R in aVL > 28 [men] or >22 mm [women]) defined ECG LVH.ECGs were available at baseline in 26,384 patients. Baseline Cornell voltage LVH was present in 1,741 (7%) patients, who were older (67.4 vs. 66.6 years, P < 0.001), more likely to be female (74 vs. 44%, P < 0001) with a higher systolic blood pressure (151 vs. 146 mm Hg, P < 0.001) than patients without ECG LVH. During 5.0 ± 1.4 years mean follow-up, baseline and in-study ECG LVH was significantly associated with 29 to 98% increased risks of all-cause mortality, MI, CHD, stroke, and HF in multivariable Cox analyses.Baseline Cornell voltage LVH is associated with increased CV morbidity and all-cause mortality in treated hypertensive patients independent of treatment modality and other CV risk factors.Trial Number NCT00000542.
Project description:BACKGROUND:It is currently unknown whether intensive blood pressure (BP) lowering beyond that recommended would lead to more lowering of the risk of left ventricular hypertrophy (LVH) in patients with hypertension and whether reducing the risk of LVH explains the reported cardiovascular disease (CVD) benefits of intensive BP lowering in this population. METHODS:This analysis included 8164 participants (mean age, 67.9 years; 35.3% women; 31.2% blacks) with hypertension but no diabetes mellitus from the SPRINT trial (Systolic Blood Pressure Intervention Trial): 4086 randomly assigned to intensive BP lowering (target SBP <120 mm?Hg) and 4078 assigned to standard BP lowering (target SBP <140 mm?Hg). Progression and regression of LVH as defined by Cornell voltage criteria derived from standard 12-lead ECGs recorded at baseline and biannually were compared between treatment arms during a median follow-up of 3.81 years. The effect of intensive (versus standard) BP lowering on the SPRINT primary CVD outcome (a composite of myocardial infarction, acute coronary syndrome, stroke, heart failure, and CVD death) was compared before and after adjustment for LVH as a time-varying covariate. RESULTS:Among SPRINT participants without baseline LVH (n=7559), intensive (versus standard) BP lowering was associated with a 46% lower risk of developing LVH (hazard ratio=0.54; 95% confidence interval, 0.43-0.68). Similarly, among SPRINT participants with baseline LVH (n=605, 7.4%), those assigned to the intensive (versus standard) BP lowering were 66% more likely to regress/improve their LVH (hazard ratio=1.66; 95% confidence interval, 1.31-2.11). Adjustment for LVH as a time-varying covariate did not substantially attenuate the effect of intensive BP therapy on CVD events (hazard ratio of intensive versus standard BP lowering on CVD, 0.76 [95% confidence interval, 0.64-0.90] and 0.77 [95% confidence interval, 0.65-0.91] before and after adjustment for LVH as a time-varying covariate, respectively). CONCLUSIONS:Among patients with hypertension but no diabetes mellitus, intensive BP lowering (target systolic BP <120 mm?Hg) compared with standard BP lowering (target systolic BP <140 mm?Hg) resulted in lower rates of developing new LVH in those without LVH and higher rates of regression of LVH in those with existing LVH. This favorable effect on LVH did not explain most of the reduction in CVD events associated with intensive BP lowering in the SPRINT trial. CLINICAL TRIAL REGISTRATION:URL: http://www.clinicaltrials.gov. Unique identifier: NCT01206062.
Project description:To assess the natural history of prehospital blood pressure (BP) during emergency medical services (EMS) transport of suspected stroke and determine whether prehospital BP differs among types of patients with suspected stroke (ischemic stroke, TIA, intracerebral hemorrhage [ICH], or stroke mimic).A retrospective, cross-sectional, observational analysis of a centralized EMS database containing electronic records of patients transported by EMS to the emergency department (ED) with suspected stroke during an 18-month period was conducted. Hospital charts and neuroimaging were utilized to determine the final diagnosis (ischemic stroke, TIA, ICH, or stroke mimic).A total of 960 patients were transported by EMS to ED with suspected stroke. Stroke was diagnosed in 544 patients (56.7%) (38.2% ischemic stroke, 12.2% TIA, 5.3% ICH) and 416 (43.2%) were considered mimics. Age-adjusted mean prehospital systolic BP (SBP) was higher in acute stroke patients (155.6 mm Hg; 95% confidence interval [CI]: 153.4-157.9 mm Hg) compared to mimics (146.1 mm Hg; 95% CI: 142.5-148.6 mm Hg; p < 0.001). Age-adjusted mean prehospital SBP was higher in ICH (172.3 mm Hg; 95% CI: 165.1-179.7 mm Hg) than in either ischemic stroke or TIA (154.7 mm Hg; 95% CI: 152.3-157.0 mm Hg; p < 0.001). Median (interquartile range) SBP drop from initial prehospital SBP to ED SBP was 4 mm Hg (-6 to 17 mm Hg). Mean prehospital SBP was strongly correlated with ED SBP (r = 0.82, p < 0.001).Prehospital SBP is higher in acute stroke relative to stroke mimics and highest in ICH. Given the stability of BP between initial EMS and ED measurements, it may be reasonable to test the feasibility and safety of prehospital antihypertensive therapy in patients with suspected acute stroke.
Project description:<h4>Introduction</h4>Half of all hypertensive individuals have inadequately-controlled BP because monitoring methods are ineffective. This single centre study examined consecutive subjects undergoing 24 hour BP measurements for clinic and ambulatory BP levels, and for end-organ damage (retinal microvascular abnormalities and left ventricular hypertrophy, LVH, > 1.1 cm). Retinal images were graded for microvascular retinopathy (Wong and Mitchell classification), and vessel calibre using a semiautomated method. Features were compared using chi-squared, Fisher's exact or the student's t test.<h4>Methods</h4>One hundred and thirty-one individuals (59 male, 45.0%, mean age 61.7 ± 14.5 years) were studied. Ninety-nine (76.2%) had a clinic BP ? 140/90 mm Hg, 84 (64.6%) had a mean awake systolic BP ? 135 mm Hg, 100 (76.9%) had a mean sleeping systolic BP ? 120 mm Hg, and 100 (76.2%) had abnormal nocturnal BP dipping patterns. Sixty-nine individuals had undergone echocardiography and 23 (33.3%) had LVH.<h4>Results</h4>All participants had a mild (88.5%) or moderate (11.5%) microvascular retinopathy. Moderate microvascular retinopathy was found in 86.7% of those with a mean awake systolic BP ?135 mm Hg (p = 0.058) but was not associated with other abnormal BP measurements, abnormal dipping patterns or LVH. However retinal arteriole calibre was reduced in subjects with a mean 24 hour awake systolic BP ? 135 mm Hg (p = 0.05). Retinal arteriole calibre was smaller in subjects with LVH (128.1 ± 13.5 ?m compared with 137.6 ± 14.1 ?m in normals, p = 0.014). Venular calibre was also less in subjects with LVH (185.4 ± 24.6 ?m compared with 203.0 ± 27.2 ?m in normals, p = 0.016). Arteriole narrowing predicted an increased risk of LVH (AUC 0.69, 95%CI 0.55 to 0.83) that was comparable with 24 hour systolic BP ?130 mm Hg (AUC 0.68, 95%CI 0.53 to 0.82) and mean awake systolic BP ?135 mm Hg (AUC 0.68, 95%CI 0.54 to 0.83).<h4>Conclusions</h4>This study suggests that retinal arteriole narrowing may be equally accurate in predicting LVH as any clinic or ambulatory BP measurement. The convenience and accuracy of microvascular calibre measurement mean that it should be investigated further for a role in routine hypertension assessment and monitoring.
Project description:This study investigated whether a mean blood pressure (BP) of <130/80 mm Hg is associated with further reduction in cardiovascular outcomes in treated hypertensive subjects with previous stroke.Subjects from the Korea National Health Insurance Service health examinee cohort diagnosed as having stroke and hypertension from January 1st, 2003 and December 31st, 2006 (N=2320) were grouped according to mean systolic (<130, 130-<140, and ?140 mm Hg) and diastolic (<80, 80-<90, and ?90 mm Hg) BP recorded during follow-up health examinations. All-cause and cardiovascular mortality over 11 years were compared. Compared with subjects with a systolic BP of ?140 mm Hg (N=736), subjects with a systolic BP of 130 to <140 mm Hg (N=793) had a significantly lower risk of all-cause death (hazard ratio [HR], 0.61; 95% confidence interval [CI], 0.47-0.79; P<0.001), cardiovascular mortality (HR, 0.39; 95% CI, 0.25-0.61; P<0.001), and fatal ischemic stroke (HR, 0.25; 95% CI, 0.10-0.63; P=0.003). Systolic BP of <130 mm Hg (N=791) was associated with lower risk of nonfatal hemorrhagic stroke. Subjects with a diastolic BP of 80 to <90 mm Hg (N=1100) had significantly lower risk of all-cause death (HR, 0.60, 95% CI, 0.45-0.80; P<0.001) and cardiovascular mortality (HR, 0.45; 95% CI, 0.30-0.70; P<0.001) than those with a diastolic BP of ?90 mm Hg (N=342). Diastolic BP of <80 mm Hg (N=878) was associated with reduced risk of nonfatal hemorrhagic stroke and further lowering of all-cause mortality and cardiovascular mortality.BP of <130/80 mm Hg was associated with improved outcomes in hypertensive subjects with previous stroke.
Project description:OBJECTIVES:To evaluate the effect of different ranges of systolic blood pressure (SBP) on left ventricular (LV) geometry and diastolic function in Chinese population. DESIGN:Cross-sectional study. SETTING:Peking Union Medical College Hospital in Beijing, China. PARTICIPANTS:All inhabitants aged 35 years or older, living in five villages of Shunyi were invited. Exclusion criteria included individuals who declined participation, presence of moderate to severe valvular heart disease, persistent atrial fibrillation and suboptimal echocardiograms. INTERVENTIONS:The baseline data of 1051 participants were analysed. The relationship between SBP and LV geometric and diastolic function assessed by echocardiography was analysed after adjusting for conventional cardiac risk factors. RESULTS:The adjusted value of SBP was independently associated with LV hypertrophy (LVH) and LV diastolic dysfunction (LVDDF) (all p<0.01). Setting individuals with SBP <120 mm Hg as the reference group (group 1), those with SBP between 120 mm Hg and 140 mm Hg (group 2) had higher risk odds of LVH and those with SBP ≥140 mm Hg (group 3) had higher risk odds of LVH and LVDDF (all p<0.01). With the increase of SBP, LV mass index (LVMI) and E/e' stepwise increased and e' stepwise decreased significantly from group 1 to 3 (all p<0.05). In the whole population, SBP was independently correlated with LVMI, LVEDD, Left Atrial Volume Index, e', and E/e' (all p<0.01). CONCLUSIONS:SBP was independently related to LVH and LVDDF, SBP between 120 and 140 mm Hg was independently related to worse LV remodelling and diastolic function, these findings indicated the potential benefit of intensive SBP control.
Project description:BACKGROUND:Regression of left ventricular hypertrophy (LVH) is feasible with more frequent hemodialysis (HD). We aimed to ascertain pathways associated with regression of left ventricular mass (LVM) in patients enrolled in the Frequent HD Network (FHN) trials. METHODS:This was a post hoc observational cohort study. We hypothesized LVH regression with frequent HD was associated with a different cardiovascular biomarker profile. Regressors were defined as patients who achieved a reduction of more than 10% in LVM at 12 months. Progressors were defined as patients who had a minimum of 10% increase in LVM at 12 months. RESULTS:Among 332 randomized patients, 243 had biomarker data available. Of these, 121 patients did not progress or regress, 77 were regressors, and 45 were progressors. Mean LVM change differed between regressors and progressors by -65.6 (-74.0 to -57.2) g, p < 0.001. Regressors had a median (interquartile range) increase in dialysis frequency (from 3.0 [3.0-3.0] to 4.9 [3-5.7] per week, p = 0.001) and reductions in pre-dialysis systolic (from 149.0 [136.0-162.0] to 136.0 [123.0-152.0] mm Hg, p < 0.001) and diastolic (from 83.0 [71.0-91.0] to 76.0 [68.0-84.0] mm Hg, p < 0.001) blood pressures. Klotho levels increased in regressors versus progressors (76.9 [10.5-143.3] pg/mL, p = 0.024). Tissue inhibitors of metalloproteinase (TIMP)-2 levels fell in regressors compared to progressors (-7,853 [-14,653 to -1,052] pg/mL, p = 0.024). TIMP-1 and log (brain natriuretic -peptide [BNP]) levels also tended to fall in regressors. Changes in LVM correlated inversely with changes in klotho (r = -0.24, p = 0.014). -Conclusions: Markers of collagen turnover and changes in klotho levels are potential novel pathways associated with regression of LVH in the dialysis population, which will require further prospective validation.
Project description:To investigate HIV, its treatment, and hypertension as stroke risk factors in Malawian adults.We performed a case-control study of 222 adults with acute stroke, confirmed by MRI in 86%, and 503 population controls, frequency-matched for age, sex, and place of residence, using Global Positioning System for random selection. Multivariate logistic regression models were used for case-control comparisons.HIV infection (population attributable fraction [PAF] 15%) and hypertension (PAF 46%) were strongly linked to stroke. HIV was the predominant risk factor for young stroke (?45 years), with a prevalence of 67% and an adjusted odds ratio (aOR) (95% confidence interval) of 5.57 (2.43-12.8) (PAF 42%). There was an increased risk of a stroke in patients with untreated HIV infection (aOR 4.48 [2.44-8.24], p < 0.001), but the highest risk was in the first 6 months after starting antiretroviral therapy (ART) (aOR 15.6 [4.21-46.6], p < 0.001); this group had a lower median CD4(+) T-lymphocyte count (92 vs 375 cells/mm(3), p = 0.004). In older participants (HIV prevalence 17%), HIV was associated with stroke, but with a lower PAF than hypertension (5% vs 68%). There was no interaction between HIV and hypertension on stroke risk.In a population with high HIV prevalence, where stroke incidence is increasing, we have shown that HIV is an important risk factor. Early ART use in immunosuppressed patients poses an additional and potentially treatable stroke risk. Immune reconstitution inflammatory syndrome may be contributing to the disease mechanisms.
Project description:Left ventricular hypertrophy (LVH), assessed by ECG, is associated with an increased risk for cardiovascular events among hypertensive subjects. We evaluated the risks of LVH in a Japanese general population including normotensive and prehypertensive subjects. We measured ECG and blood pressure in 10 755 subjects at baseline. The Cornell product (CP) and Sokolow-Lyon (SL) voltage were calculated as markers of LVH (CP >or=2440 mm x ms and SL voltage >or=38 mm). Follow-up was performed for 10 years, and the incidence of stroke and myocardial infarction was evaluated. The prevalence of CP-LVH was 2.7% for normotensives, 5.2% for prehypertensives, and 11.0% for hypertensives, and the prevalence of SL-LVH was 5.0%, 8.2%, and 15.2%, respectively. In all of the subjects, CP-LVH and SL-LVH were both predictors of stroke (CP-LVH: hazard risk: 1.62, 95% CI: 1.19 to 2.20, P=0.002; SL-LVH: hazard risk: 1.29, 95% CI: 0.98 to 1.71, P=0.07) after adjustment for confounding factors but were not predictors of myocardial infarction. The adjusted hazard ratio of CP-LVH predicting stroke was especially high in the normotensives (hazard risk: 7.53; 95% CI: 3.39 to 16.77). In the normotensives, diabetes mellitus and hyperlipidemia were significant determinants of CP-LVH but not of SL-LVH. In all of the hypertensive subgroups (normotensives, prehypertensives, and hypertensives), the c-statistic for the equation predicting stroke increased when CP-LVH was added to the model but not when SL-LVH was added. In conclusion, both CP-LVH and SL-LVH are risk factors for stroke in the Japanese general population. CP-LVH is related to glucose abnormality, and its predictive value for stroke is seen even in normotensives and prehypertensives.
Project description:Aldosterone infusion results in left ventricular hypertrophy (LVH) and hypertension and may involve profibrotic and proinflammatory mechanisms. In turn, hypertension is the major cause of diastolic heart failure (HF). Adiponectin, an adipose-derived plasma protein, exerts antiinflammatory and anti-hypertrophic effects and is implicated in the development of hypertension and systolic HF. We thus tested the hypothesis that hypoadiponectinemia in aldosterone-induced hypertension exacerbated cardiac remodeling and diastolic HF. Wild-type (WT) or adiponectin-deficient (APNKO) mice underwent saline or aldosterone infusion and uninephrectomy and were fed 1% salt water for 4 wk. Blood pressure was increased in aldosterone-infused WT (132 +/- 2 vs. 109 +/- 3 mm Hg; P < 0.01) and further augmented in APNKO mice (140 +/- 3 mm Hg; P < 0.05 vs. aldosterone-infused WT). LVH was increased in aldosterone-infused WT vs. WT mice (LV/body weight ratio, 4.8 +/- 0.2 vs. 4.1 +/- 0.2 mg/g) and further increased in aldosterone-infused APNKO mice (LV/body weight ratio, 6.0 +/- 0.4 mg/g). Left ventricular ejection fraction was not decreased in either aldosterone-infused WT or APNKO hearts. Pulmonary congestion however was worse in APNKO mice (P < 0.01). The ratio of early ventricular filling over late ventricular filling (E/A) and the ratio of mitral peak velocity of early filling to early diastolic mitral annular velocity (E/e'), measures of diastolic function, were increased in aldosterone-infused WT hearts and further increased in APNKO hearts (P < 0.05 for both). Renal function and cardiac fibrosis were no different between both aldosterone-infused groups. Aldosterone increased matrix metalloproteinase-2 expression in WT hearts (P < 0.05 vs. WT and P < 0.01 vs. APNKO). Myocardial atrial natriuretic peptide, interferon-gamma, and TNF-alpha expression were increased in aldosterone-infused WT hearts. Expression of these proteins was further increased in aldosterone-infused APNKO hearts. Therefore, hypoadiponectinemia in hypertension-induced diastolic HF exacerbates LVH, diastolic dysfunction, and diastolic HF. Whether or not adiponectin replacement prevents the progression to diastolic HF will warrant further study.