Cancer cell line microarray as a novel screening method for identification of radioresistance biomarkers in head and neck squamous cell carcinoma.

BACKGROUND: Currently, no clinically useful biomarkers for radioresistance are available in head and neck squamous cell carcinoma (HNSCC). This study assesses the usefulness of Cell Line Microarray (CMA) method to enhance immunohistochemical screening of potential immunohistochemical biomarkers for radioresistance in HNSCC cell lines. METHODS: Twenty-nine HNSCC cell lines were cultured, cell pellets formalin-fixed, paraffin-embedded, and arrayed. Radioresistance features of the cell lines were combined to immunohistochemical stains for p53, NDFIP1, EGFR, stem cell marker Oct4, and PP2A inhibitor CIP2A. RESULTS: Expression of p53, EGFR or CIP2A did not indicate intrinsic radioresistance in vitro. Stem cell marker Oct4 nuclear positivity and NDFIP1 nuclear positivity was correlated with increased intrinsic radioresistance. CONCLUSION: The usefulness of CMA in analysis of HNSCC cell lines and discovery of biomarkers is demonstrated. CMA is very well adapted to both testing of antibodies in a large panel of cell lines as well as correlating staining results with other cell line characteristics. In addition, CMA-based antibody screening proved an efficient and relatively simple method to identify potential radioresistance biomarkers in HNSCC.

Age of Hypertension Onset: Overview of Research and How to Apply in Practice.

PURPOSE OF REVIEW: To review the current evidence on research related to age of hypertension onset-its definition, correlates, heritability, and association with adverse outcomes. We also propose a framework for implementing assessment of hypertension onset age into clinical practice. RECENT FINDINGS: Prior studies have used both objective measurements and self-report to determine age of hypertension onset or early-onset hypertension. Yet, no criterion for standard definition currently exists for either. Data from epidemiological and clinical studies demonstrate that early-onset hypertension is a highly heritable trait that confers an increased risk for cardiovascular death and end-organ damage compared with late-onset hypertension. Literature to date suggests that (parental) age of hypertension onset can be feasibly assessed for estimating (1) risk of future hypertension in non-hypertensive persons; and (2) the propensity for cardiovascular disease in individuals with established hypertension.

Association between self-reported hypertension onset age and electrocardiographic left ventricular hypertrophy.

Objectively defined early-onset hypertension, based on repeated blood pressure measurements, is associated with greater odds of organ damage and cardiovascular mortality than late-onset hypertension. In this study we examined the association between two factors that are easily available in primary care, self-reported hypertension onset age and electrocardiographic left ventricular hypertrophy (ECG-LVH), in a nationwide population sample of 2864 Finns aged ≥50 years. We observed that, in contrast to prior findings, the odds of ECG-LVH were similar between self-reported hypertension onset age groups, and thus self-reported early-onset hypertension does not seem to associate with ECG-LVH more strongly than simple presence of hypertension.

Clinical Correlates of Early-Onset Hypertension.

BACKGROUND: Early-onset hypertension has been established as a heritable trait and a risk factor for cardiovascular disease outcomes. However, the clinical correlates of early-onset hypertension remain unidentified. METHODS: In this study, we assessed the demographic characteristics and lifestyle factors related to hypertension onset age in a sample of 3,286 Coronary Artery Risk Development in Young Adults (CARDIA) study participants (mean baseline age 25 ± 4 years, 57% women). We examined the association between the participants' baseline characteristics and age of hypertension onset subgroups (<35, 35‒44, or ≥45 years) using a multinomial logistic regression model with those who did not develop hypertension as the reference group. Hypertension onset was defined as blood pressure ≥140/90 mm Hg or antihypertensive medication use on 2 consecutively attended follow-up visits. RESULTS: In the multinomial logistic regression model, individuals who were black (odds ratio [OR], 5.08; 95% confidence interval [CI], 3.17-8.14), were more obese (OR, 1.57; 95% CI, 1.32-1.88), or had higher total cholesterol (OR, 1.34; 95% CI, 1.13-1.60 per SD) had increased odds of early-onset hypertension (onset at <35 years) vs. not developing hypertension. In contrast, 1-SD higher high-density lipoprotein (HDL)-cholesterol was related to decreased odds of early-onset hypertension (OR, 0.71; 95% CI, 0.57-0.89). The odds for having earlier hypertension onset increased linearly across age of onset categories in black individuals and individuals with lower HDL-cholesterol (P < 0.05 for trend for both). CONCLUSIONS: Our findings suggest that individuals who are black, obese, have higher total cholesterol, or have lower HDL-cholesterol level, are potentially at an increased risk of having early-onset hypertension.

Early-but Not Late-Onset Hypertension Is Related to Midlife Cognitive Function.

Hypertension is related to increased risk of cognitive decline in a highly age-dependent manner. However, conflicting evidence exists on the relation between age of hypertension onset and cognition. Our goal was to investigate the association between early- versus late-onset hypertension and midlife cognitive performance in 2946 CARDIA study (Coronary Artery Risk Development in Young Adults) participants (mean age 55±4, 57% women). The participants underwent 9 repeat examinations, including blood pressure measurements, between 1985 to 1986 and 2015 to 2016. The participants underwent brain magnetic resonance imaging and completed Digit Symbol Substitution Test, Rey Auditory Verbal Learning Test, Stroop interference test, and the Montreal Cognitive Assessment to evaluate cognitive function at the year 30 exam. We assessed the relation between age of hypertension onset and cognitive function using linear regression models adjusted for cognitive decline risk factors, including systolic blood pressure. We observed that individuals with early-onset hypertension (onset at <35 years) had 0.24±0.09, 0.22±0.10, 0.27±0.09, and 0.19±0.07 lower standardized Z-scores in Digit Symbol Substitution Test, Stroop test, Montreal Cognitive Assessment, and a composite cognitive score than participants without hypertension (P<0.05 for all). In contrast, hypertension onset at ≥35 years was not associated with cognitive function (P >0.05 for all). In a subgroup of 559 participants, neither early- nor late-onset hypertension was related to macrostructural brain alterations (P >0.05 for all). Our results indicate that early-onset hypertension is a potent risk factor for midlife cognitive impairment. Thus, age of hypertension onset assessment in clinical practice could improve risk stratification of cognitive decline in patients with hypertension.

Polygenic Risk Scores Predict Hypertension Onset and Cardiovascular Risk.

Although genetic risk scores have been used to predict hypertension, their utility in the clinical setting remains uncertain. Our study comprised N=218 792 FinnGen participants (mean age 58 years, 56% women) and N=22 624 well-phenotyped FINRISK participants (mean age 50 years, 53% women). We used public genome-wide association data to compute polygenic risk scores (PRSs) for systolic and diastolic blood pressure (BP). Using time-to-event analysis, we then assessed (1) the association of BP PRSs with hypertension and cardiovascular disease (CVD) in FinnGen and (2) the improvement in model discrimination when combining BP PRSs with the validated 4- and 10-year clinical risk scores for hypertension and CVD in FINRISK. In FinnGen, compared with having a 20 to 80 percentile range PRS, a PRS in the highest 2.5% conferred 2.3-fold (95% CI, 2.2­2.4) risk of hypertension and 10.6 years (95% CI, 9.9­11.4) earlier hypertension onset. In subgroup analyses, this risk was only 1.6-fold (95% CI, 1.5­1.7) for late-onset hypertension (age ≥55 years) but 2.8-fold (95% CI, 2.6­2.9) for early-onset hypertension (age <55 years). Elevated systolic BP PRS also conferred 1.3-fold (95% CI, 1.2­1.4) risk of CVD and 2.3 years (95% CI, 1.6­3.1) earlier onset. In FINRISK, systolic and diastolic BP PRSs improved clinical risk prediction of hypertension (but not CVD), increasing the C statistics by 0.7% (95% CI, 0.3­1.1). We demonstrate that genetic information improves hypertension risk prediction. BP PRSs together with traditional risk factors could improve prediction of hypertension and particularly early-onset hypertension, which confers substantial CVD risk.

Longitudinal blood pressure patterns and cardiovascular disease risk.

Observational and interventional studies have unequivocally demonstrated that "present", i.e. single-occasion, blood pressure is one of the key determinants of cardiovascular disease risk. Over the past two decades, however, numerous publications have suggested that longitudinal blood pressure data and assessment of long-term blood pressure exposure provide incremental prognostic value over present blood pressure. These studies have used several different indices to quantify the overall exposure to blood pressure, such as time-averaged blood pressure, cumulative blood pressure, blood pressure trajectory patterns, and age of hypertension onset. This review summarises existing research on the association between these indices and hard cardiovascular outcomes, outlines the strengths and weaknesses of these indices, and provides an overview of how longitudinal blood pressure changes can be measured and used to improve cardiovascular disease risk prediction.KEY MESSAGESNumerous recent publications have examined the relation between cardiovascular disease and long-term blood pressure (BP) exposure, quantified using indices such as time-averaged BP, cumulative BP, BP trajectory patterns, and age of hypertension onset.This review summarises existing research on the association between these indices and hard cardiovascular outcomes, outlines the strengths and weaknesses of these indices, and provides an overview of how longitudinal BP changes can be measured and used to improve cardiovascular disease risk prediction.Although longitudinal BP indices seem to predict cardiovascular outcomes better than present BP, there are considerable differences in the clinical feasibility of these indices along with a limited number of prospective data.

Self-reported Age of Hypertension Onset and Hypertension-Mediated Organ Damage in Middle-Aged Individuals.

BACKGROUND: Objectively defined early onset hypertension, based on repeated blood pressure measurements, is a strong risk factor for cardiovascular disease (CVD). We aimed to assess if also self-reported hypertension onset age is associated with hypertension-mediated organ damage (HMOD). Additionally, we evaluated the agreement between self-reported and objectively defined hypertension onset age. METHODS: We studied 2,649 participants (50 ± 4 years at the time of outcome assessment, 57% women) of the Coronary Artery Risk Development in Young Adults (CARDIA) study who underwent measurements for echocardiographic left ventricular hypertrophy (LVH), left ventricular diastolic dysfunction (LVDD), coronary calcification, and albuminuria. We divided the participants into groups according to self-reported hypertension onset age (<35 years, 35-44 years, ≥45 years, and no hypertension). We used multivariable-adjusted logistic regression models to assess the relation between self-reported hypertension onset age with the presence of HMOD, with those who did not report hypertension as the referent group. RESULTS: Compared with individuals without self-reported hypertension, self-reported hypertension onset at <35 years was associated with LVH (odds ratio (OR), 2.38; 95% confidence interval (CI), 1.51-3.76), LVDD (OR, 2.32; 95% CI, 1.28-4.18, coronary calcification (OR, 2.87; 95% CI, 1.50-5.47), and albuminuria (OR, 1.62; 95% CI, 0.81-3.26). Self-reported hypertension onset at ≥45 years was only associated with LVDD (OR, 1.81; 95% CI, 1.06-3.08). The agreement between self-reported and objectively defined hypertension onset age groups was 78-79%. CONCLUSIONS: Our findings suggest that self-reported hypertension onset age, a pragmatically feasible assessment in clinical practice, is a reasonable method for assessing risk of HMOD and CVD.

Early Onset Hypertension Is Associated With Hypertensive End-Organ Damage Already by MidLife.

Early onset hypertension confers increased risk for cardiovascular mortality in the community. Whether early onset hypertension also promotes the development of target end-organ damage (TOD), even by midlife, has remained unknown. We studied 2680 middle-aged CARDIA study (Coronary Artery Risk Development in Young Adults) Study participants (mean age 50±4 years, 57% women) who underwent up to 8 serial blood pressure measurements between 1985 and 2011 (age range at baseline 18-30 years) in addition to assessments of echocardiographic left ventricular hypertrophy, coronary calcification, albuminuria, and diastolic dysfunction in 2010 to 2011. Age of hypertension onset was defined as the age at first of 2 consecutively attended examinations with blood pressure ≥140/90 mm Hg or use of antihypertensive medication. Participants were divided in groups by hypertension onset age (<35 years, 35-44 years, ≥45 years, or no hypertension). While adjusting for TOD risk factors, including systolic blood pressure, we used logistic regression to calculate odds ratios for cases (participants with TOD) versus controls (participants without TOD) to examine the relation of hypertension onset age and hypertensive TOD. Compared with normotensive individuals, hypertension onset at age <35 years was related to odds ratios of 2.29 (95% CI, 1.36-3.86), 2.94 (95% CI, 1.57-5.49), 1.12 (95% CI, 0.55-2.29), and 2.06 (95% CI, 1.04-4.05) for left ventricular hypertrophy, coronary calcification, albuminuria, and diastolic dysfunction, respectively. In contrast, hypertension onset at age ≥45 years was not related to increased odds of TOD. Our findings emphasize the importance of assessing age of hypertension onset in hypertensive patients to identify high-risk individuals for preventing hypertensive complications.