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A parallel physiological pathway for elastic changes is hypothesized for declines in arterial elasticity and lung function. Endothelial dysfunction and inflammation could potentially decrease elasticity of both vasculature and lung tissue. We examined biomarkers, large arterial elasticity and small arterial elasticity (SAE), and forced vital capacity (FVC) in a period cross-sectional design in the multiethnic study of atherosclerosis, which recruited 1823 women and 1803 men, age range 45 to 84 years, black, white, Hispanic, and Chinese, free of clinically recognized cardiovascular disease. Radial artery tonometric pulse waveform registration was performed and large arterial elasticity and SAE were derived from diastole. Spirometric data and markers of endothelial dysfunction and inflammation (soluble intracellular adhesion molecule-1, fibrinogen, hs-C-reactive protein, and interleukin-6) were obtained. Mean large arterial elasticity was 13.7 ± 5.5 mL/mm Hg × 10 and SAE was 4.6 ± 2.6 mL/mm Hg × 100. Mean FVC was 3192 ± 956.0 mL and forced expiratory volume in 1 second was 2386 ± 734.5 mL. FVC was about 40 ± 5 mL higher per SD of SAE, stronger in men than women. The association was slightly weaker with large arterial elasticity, with no sex interaction. After regression adjustment for demographic, anthropometric, and cardiovascular risk factors, the biomarkers tended to be related to reduced SAE and FVC, particularly in men. These biomarker associations suggest important cardiovascular disease risk alterations that occur concurrently with lower arterial elasticity and lung function. The observed positive association of SAE with FVC and with forced expiratory volume in 1 second in middle-aged to older free-living people is consistent with the hypothesis of parallel physiological pathways for elastic changes in the vasculature and in lung parenchymal tissue. [ABSTRACT FROM AUTHOR]

Lung function studies in middle-aged subjects predict cardiovascular disease mortality. We studied whether greater loss of forced vital capacity (FVC) early in life predicted incident hypertension. The sample was 3205 black and white men and women in the Coronary Artery Risk Development in Young Adults Study examined between 1985 and 1986 (Coronary Artery Risk Development in Young Adults year 0, ages 18-30 years) and 2005-2006 and who were not hypertensive by year 10. FVC was assessed at years 0, 2, 5, 10, and 20. Proportional hazard ratios and linear regression models predicted incident hypertension at years 15 or 20 (n=508) from the change in FVC (FVC at year 10 - peak FVC, where peak FVC was estimated as the maximum across years 0, 2, 5, and 10). Covariates included demographics, center, systolic blood pressure, FVC maximum, smoking, physical activity, asthma, and body mass index. Unadjusted cumulative incident hypertension was 25% in the lowest FVC loss quartile (Q1; median loss: 370 mL) compared with 12% cumulative incident hypertension in those who achieved peak FVC at year 10 (Q4). Minimally adjusted hazard ratio for Q1 versus Q4 was 2.21 (95% CI: 1.73-2.83), and this association remained significant in the fully adjusted model (1.37; 95% CI: 1.05-1.80). Decline in FVC from average age at peak (29.4 years) to 35 years old predicted incident hypertension between average ages 35 and 45 years. The findings may represent a common pathway that may link low normal FVC to cardiovascular disease morbidity and mortality. [ABSTRACT FROM AUTHOR]

Background: Recent American College of Cardiology/American Heart Association Primary Prevention Guidelines recommended considering low-dose aspirin therapy only among adults 40 to 70 years of age who are at higher atherosclerotic cardiovascular disease (ASCVD) risk but not at high risk of bleeding. However, it remains unclear how these patients are best identified. The present study aimed to assess the value of coronary artery calcium (CAC) for guiding aspirin allocation for primary prevention by using 2019 aspirin meta-analysis data on cardiovascular disease relative risk reduction and bleeding risk., Methods: The study included 6470 participants from the MESA Study (Multi-Ethnic Study of Atherosclerosis). ASCVD risk was estimated using the pooled cohort equations, and 3 strata were defined: <5%, 5% to 20%, and >20%. All participants underwent CAC scoring at baseline, and CAC scores were stratified as =0, 1 to 99, ≥100, and ≥400. A 12% relative risk reduction in cardiovascular disease events was used for the 5-year number needed to treat (NNT 5 ) calculations, and a 42% relative risk increase in major bleeding events was used for the 5-year number needed to harm (NNH 5 ) estimations., Results: Only 5% of MESA participants would qualify for aspirin consideration for primary prevention according to the American College of Cardiology/American Heart Association guidelines and using >20% estimated ASCVD risk to define higher risk. Benefit/harm calculations were restricted to aspirin-naive participants <70 years of age not at high risk of bleeding (n=3540). The overall NNT 5 with aspirin to prevent 1 cardiovascular disease event was 476 and the NNH 5 was 355. The NNT 5 was also greater than or similar to the NNH 5 among estimated ASCVD risk strata. Conversely, CAC≥100 and CAC≥400 identified subgroups in which NNT 5 was lower than NNH 5 . This was true both overall (for CAC≥100, NNT 5 =140 versus NNH 5 =518) and within ASCVD risk strata. Also, CAC=0 identified subgroups in which the NNT 5 was much higher than the NNH 5 (overall, NNT 5 =1190 versus NNH 5 =567)., Conclusions: CAC may be superior to the pooled cohort equations to inform the allocation of aspirin in primary prevention. Implementation of current 2019 American College of Cardiology/American Heart Association guideline recommendations together with the use of CAC for further risk assessment may result in a more personalized, safer allocation of aspirin in primary prevention. Confirmation of these findings in experimental settings is needed.

Background: Atrial fibrosis is a hallmark of structural remodeling in atrial fibrillation (AF). Plasma procollagen type III N-terminal propeptide (PIIINP) reflects collagen synthesis and degradation while collagen type I carboxy-terminal telopeptide (ICTP) reflects collagen degradation. We aimed to study baseline plasma PIIINP and ICTP and their associations with incident AF in participants initially free of overt cardiovascular disease., Methods: In a stratified sample of the Multi-Ethnic Study of Atherosclerosis, initially aged 45-84 years, 3071 participants had both PIIINP and ICTP measured at baseline. Incident AF in 10-year follow-up was based on a hospital International Classification of Diseases code for AF or atrial flutter, in- or outpatient Medicare claims through 2011 (primarily in those aged 65-84 years), or ECG 10 years after baseline (n=357). The associations of PIIINP and ICTP with incident AF were estimated using Poisson regression with follow-up time offset., Results: Baseline PIIINP (5.50±1.55 µg/L) and ICTP (mean±SD, 3.41±1.37 µg/L) were positively related (both P<0.0001) to incident AF in a model adjusting for age, race/ethnicity, and sex, with an apparent threshold (relative incidence density 2.81 [1.94-4.08] for PIIINP ≥8.5 µg/L [3.5% of the sample] and 3.46 [2.36-5.07] for ICTP ≥7 µg/L [1.7% of the sample]). Findings were attenuated but remained statistically significant after further adjustment for systolic blood pressure, height, body mass index, smoking, and renal function. Additional adjustment for other risk factors and biomarkers of inflammation did not alter conclusions., Conclusions: Plasma collagen biomarkers, particularly at elevated levels, were associated with excess risk for AF.

Background: Studies suggest a link between vascular injuries and dementia. Only a few studies, however, examined a longitudinal relation of subclinical vascular disease with dementia. We tested whether baseline coronary artery calcium (CAC), a biomarker of subclinical vascular disease, is associated with incident dementia independent of vascular risk factors and APOE-ε4 genotype in a community-based sample., Methods and Results: We analyzed 6293 participants of MESA (Multi-Ethnic Study of Atherosclerosis), aged 45 to 84 years at baseline (2000-2002), initially free of cardiovascular disease and noticeable cognitive deficit. Dementia cases were identified using hospital and death certificate International Statistical Classification of Diseases and Related Health Problems codes. Cox models were used to obtain hazard ratios according to CAC category, or per 1 SD log2[CAC+1], adjusted for vascular risk factor, APOE-ε4, with or without exclusion of interim stroke or cardiovascular disease. We observed 271 dementia cases in a median follow-up of 12.2 years. Baseline CAC had a graded positive association with dementia risk. Compared with no CAC, CAC score of 1 to 400, 401 to 1000, and ≥1001 had increased risk of dementia by 23%, 35%, and 71%, respectively, ( P trend =0.026) after adjustment. 1 SD higher log2[CAC+1] was associated with 24% (95% confidence interval, 8%-41%; P =0.002) increase in dementia risk. Although the association was partially explained by interim stroke/cardiovascular disease, it remained significant even after excluding the interim events, or regardless of baseline age., Conclusions: Higher baseline CAC was significantly associated with increased risk of dementia independent of vascular risk factor, APOE-ε4, and incident stroke. This is consistent with a hypothesis that vascular injuries play a role in the development of dementia., (© 2017 American Heart Association, Inc.)

Background: Aspirin for the primary prevention of coronary heart disease (CHD) is only recommended for individuals at high risk for CHD although the majority of CHD events occur in individuals who are at low to intermediate risk., Methods and Results: To estimate the potential of coronary artery calcium (CAC) scoring to guide aspirin use for primary prevention of CHD, we studied 4229 participants from the Multi-Ethnic Study of Atherosclerosis who were not on aspirin at baseline and were free of diabetes mellitus. Using data from median 7.6-year follow-up, 5-year number-needed-to-treat estimations were calculated by applying an 18% relative CHD reduction to the observed event rates. This was contrasted to 5-year number-needed-to-harm estimations based on the risk of major bleeding reported in an aspirin meta-analysis. Results were stratified by a 10% 10-year CHD Framingham Risk Score (FRS). Individuals with CAC≥100 had an estimated net benefit with aspirin regardless of their traditional risk status (estimated 5-year number needed to treat of 173 for individuals <10% FRS and 92 for individuals ≥10% FRS, estimated 5-year number needed to harm of 442 for a major bleed). Conversely, individuals with zero CAC had unfavorable estimations (estimated 5-year number needed to treat of 2036 for individuals <10% FRS and 808 for individuals ≥10% FRS, estimated 5-year number needed to harm of 442 for a major bleed). Sex-specific and age-stratified analyses showed similar results., Conclusions: For the primary prevention of CHD, Multi-Ethnic Study of Atherosclerosis participants with CAC≥100 had favorable risk/benefit estimations for aspirin use while participants with zero CAC were estimated to receive net harm from aspirin., (© 2014 American Heart Association, Inc.)

Background: Stage 2 hypertension often requires combination antihypertensive therapy. Ambulatory blood pressure monitoring (ABPM) is a useful tool for studying antihypertensive drugs and their combinations., Objective: This multicenter, double-blind, parallel-group, prompted-titration study of patients of at least 70 years of age with systolic hypertension compared the efficacy of valsartan, hydrochlorothiazide, and their combination on ambulatory blood pressure (ABP) reduction., Methods: After a 3-14-day washout, patients with systolic blood pressure of 150-200 mmHg were randomized (1 : 1 : 1) to initially receive once-daily valsartan/hydrochlorothiazide 160/12.5 mg combination therapy, hydrochlorothiazide 12.5 mg monotherapy, or valsartan 160 mg monotherapy. Prompted uptitration of patients in whom BP was more than or equal to 140/90 mmHg was performed after 4, 8, and 12 weeks of treatment. ABPM was performed at baseline and weeks 4 and 16 (study end)., Results: In this ABPM substudy (n=108), initiation of treatment with valsartan/hydrochlorothiazide lowered ABP more effectively than either monotherapy throughout the daytime, night-time, and 24-h monitoring periods, as well as during the last 4 and 6-h dosing periods. Twenty-four-hour ABP was reduced from 141.1/76.5 mmHg at baseline to 125.8/69.2 mmHg at week 4 (primary time point) with valsartan/hydrochlorothiazide compared with reductions from 142.2/78.7 to 139.1/77.5 mmHg with hydrochlorothiazide and 142.2/78.3 to 136.4/75.1 mmHg with valsartan (all P<0.01 in favor of combination therapy). In the overall study, tolerability was similar among the three treatment groups., Conclusion: In elderly hypertensives, starting combination therapy with valsartan/hydrochlorothiazide provides more effective 24-h blood pressure control than the monotherapy components, with few therapy-related side-effects.

Background: Cardiovascular disease (CVD) is increasing in HIV-infected patients. N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a significant predictor of CVD in the general population. We aimed to quantify the risk of CVD events associated with NT-proBNP at baseline in the Strategies for Management of Anti-Retroviral Therapy study., Methods: In a nested case-control study, NT-proBNP was measured at baseline in 186 patients who experienced a CVD event over an average of 2.8 years of follow-up and in 329 matched controls. Odds ratios (ORs) associated with baseline levels of NT-proBNP for CVD were estimated using conditional logistic regression., Results: At baseline median NT-proBNP [interquartile range (IQR)] was 48.1 (18.5, 112.9) pg/ml in patients who developed a CVD event and 25.7 (12.4, 50.2) pg/ml in controls. The unadjusted OR for the highest versus the lowest quartile was 3.7 [95% confidence interval (CI) 2.1-6.5, P < 0.0001]. After adjustment for baseline covariates and CVD risk factors, OR was 2.8 (95% CI 1.4-5.6, P = 0.003); with additional adjustment for IL-6, high-sensitivity C-reactive protein and D-dimer, OR was 2.3 (95% CI 1.1-4.9, P = 0.02)., Conclusions: Higher levels of NT-proBNP are associated with increased risk of CVD in HIV patients after considering established CVD risk factors and markers for inflammation and thrombosis.

Background: There are contradictory reports regarding the effects of protease inhibitors on the ECG measures of QT and PR interval durations. The effect of interrupting use of protease inhibitors on QT and PR progression is also unknown., Methods: This analysis included 3719 participants from the Strategies for Management of Antiretroviral Therapy (SMART) study, of whom 1879 were randomized to receive intermittent antiretroviral therapy (ART) (drug conservation group), whereas the rest received these drugs continuously (viral suppression group). Linear regression analysis was used to compare four ritonavir-boosted protease inhibitor (protease inhibitor/r) regimens [saquinavir (SQV/r), lopinavir (LPV/r), atazanavir (ATV/r), and other protease inhibitor/r], and nonboosted protease inhibitor regimens with nonnucleoside reverse transcriptase inhibitor (NNRTI) regimens for Bazett's (QTcB) and Fredericia's (QTcF) heart rate corrected QT and PR. Changes in QTcB, QTcF, and PR after 12 and 24 months of randomization were compared in the drug conservation group and viral suppression group., Results: Average levels of QTcB, QTcF, and PR duration at entry were 415, 406, and 158 ms. At study entry, 49% of participants were taking an NNRTI (no protease inhibitor)-based regimen and 31% were prescribed a boosted protease inhibitor, the most common being LPV/r. After adjustment for baseline factors, QTcB and QTcF levels did not vary by boosted protease inhibitor group (P = 0.26 and P = 0.34, respectively). For those given any of the boosted protease inhibitors, QTcB was 1.5 ms lower than the NNRTI group (P = 0.04). Both boosted and nonboosted protease inhibitor-containing regimens were significantly associated (P < 0.01 for each) with longer PR intervals compared to the NNRTI group. After adjustment, the difference between boosted protease inhibitors and the NNRTI group was 5.11 ms (P < 0.01); for nonboosted protease inhibitors, this difference was 3.00 ms (P < 0.01). Following ART interruption, PR duration declined for both the boosted and nonboosted protease inhibitor groups and compared to the viral suppression group, significant changes in PR interval were observed 24 months after ART interruption of boosted protease inhibitors (P < 0.01)., Conclusion: Different protease inhibitor-based regimens have a similar, minimal effect on QT compared to NNRTI-based regimens. All protease inhibitor-based regimens (boosted and nonboosted) were associated with prolongation of PR, and interruption of protease inhibitor regimens reduced the prolonged PR duration. Further research is needed to confirm the findings of this study and assess the clinical relevance of the differences.

Objective: The aim of this report was to describe the reproducibility of arterial elasticity parameters derived from radial artery diastolic pulse contour analysis., Methods: Two measurements were taken on the same day by the same technician with the HDI/Pulsewave CR-2000 System on each of a subset of participants selected randomly from the Multi-Ethnic Study of Atherosclerosis. Large and small artery elasticities (C1 and C2), C1 and C2 each multiplied by systemic vascular resistance (C1xR and C2xR, which are functions of the radial artery pulse waveform only), and systolic and diastolic blood pressures (SBP and DBP) were evaluated., Results: Two measurements were taken of each of the 131 participants. The mean difference±standard deviation of the difference was -0.13±3.5 mmHg ×10 for C1, -0.03±1.5 mmHg ×100 for C2, 0.10±4.6 s ×10 for C1xR, 0.05±1.8 s ×100 for C2xR, 2.8±8.2 mmHg for SBP, and 1.5±5.0 mmHg for DBP. The between-measure correlation was 0.74 for C1, 0.84 for C2, 0.58 for C1xR, 0.74 for C2xR, 0.90 for SBP, and 0.86 for DBP., Conclusion: The reproducibility of arterial elasticity measurements is less than that of SBP and DBP . Multiple measurements of arterial elasticity of a participant are recommended.

Background: Many cases of refractory hypertension cannot be attributed to specific identifiable factors. Haptoglobin polymorphism has been suggested as a candidate genetic marker in essential hypertension. The aim of this study was to investigate the distribution of haptoglobin types in patients with refractory hypertension., Methods: Haptoglobin polymorphism was studied in 383 patients with non-refractory and 62 patients with refractory hypertension. Haptoglobin was typed using starch gel electrophoresis of haemoglobin-supplemented serum., Results: In the group of patients with refractory hypertension, the relative allele frequency of haptoglobin 1 (0.266) was lower than in the group with non-refractory hypertension (0.385: P < or = 0.05). The relative frequency of haptoglobin 2-2 was 39% in the non-refractory compared with 56% in the refractory group (P < or = 0.05). In the latter group, the relative frequency of haptoglobin 2-2 was highest (75%) in patients requiring medication with four classes of drug., Conclusion: Hypertension patients with the haptoglobin 2-2 phenotype are at higher risk of developing refractory hypertension than those with other haptoglobin phenotypes.

It is not known whether there are vascular changes in the peripheral circulation of patients with orthostatic hypotension and patients with constitutional hypotension. Therefore, blood flow was studied simultaneously at the calf (mainly muscle circulation) and at the finger (mainly finger circulation) with ECG-triggered venous occlusion plethysmography. Calf and finger blood flow were measured for 20 min at rest and during reactive hyperaemia due to an arterial occlusion for 3 min. Vascular resistance was calculated from the blood flow and arterial blood pressure. In orthostatic hypotension there is a decreased vasodilator capacity of the calf resistance vessels and not of the finger resistance vessels. In constitutional hypotension there is a decreased vasodilator capacity of the calf and finger resistance vessels. These results suggest that there are structural or functional changes, or both, in the muscle and skin circulation of patients with constitutional hypotension, whereas there are only structural or functional changes, or both, in the muscle circulation of patients with orthostatic hypotension.