Hypothyroidism in coronary heart disease and its relation to selected risk factors

Otto Mayer Jr1, Jaroslav Šimon1, Jan Filipovský1, Markéta Plášková2, Richard Pikner11Center of Preventive Cardiology, 2nd Department of Internal Medicine, Charles University, Medical Faculty, Plze , Czech Republic; 2Department of Preventive Cardiology, Institute for Clinical and Experimental Medicine, Prague, Czech RepublicIntroduction: Hypothyroidism (HT) has been found a predictor of cardiovascular diseases. We aimed to ascertain the prevalence of HT in patients with manifest coronary heart disease (CHD), and to establish its association with conventional risk factors.Methods: 410 patients, 6–24 months after hospitalization for acute coronary syndrome, and/or revascularization, were included into the cross-sectional study.Results: The prevalence of thyroid dysfunction was found in males and females as follows: overt HT, ie, thyroid stimulating hormone (TSH) > 3.65 mIU/L and free thyroxine (fT4) < 9 pmol/L and/or L-thyroxine substitution, in 2.6% and 8.4%, respectively; subclinical HT (TSH >3.65, fT4 9–23 and no substitution) in 4.3% and 15.0%, respectively. Higher prevalence of HT was found in females with hypercholesterolemia, and in males and females with concomitant positive thyroid peroxydase antibodies. Hypothyroid subjects had higher total homocysteine in both genders and von Willebrand factor in males only. Hypothyroid females had higher total  and LDL cholesterol, and were more often treated for diabetes.Conclusions: HT was found highly prevalent in patient with clinical coronary heart disease, mainly in females, and was associated with several cardiovascular risk factors.Keywords: hypothyroidism, coronary heart disease, cholesterol, homocysteine, diabete

The Prognostic Impact of Renal Function Decline during Hospitalization for Heart Failure

Introduction: We aimed to evaluate the prognostic impact of renal insufficiency and fluctuation of glomerular filtration observed during hospitalization for heart failure (HF). Methods: We followed 3,639 patients hospitalized for acute HF and assessed the mortality risk associated with moderate or severe renal insufficiency, either permanent or transient. Results: After adjustment, severe renal failure defined as estimated glomerular filtration (eGFR) <30 mL/min indicates ≈60% increase in 5-year mortality risk. Similar risk also had patients with only transient decline of eGFR to this range. In contrast, we did not observe any apparent mortality risk attributable to mild/moderate renal insufficiency (eGFR 30–59.9 mL/min), regardless of whether it was transient or permanent. Conclusion: Even transient severe renal failure during hospitalization indicates poor long-term prognosis of patients with manifested HF. In contrast, only moderate renal insufficiency observed during hospitalization has no additive long-term mortality impact

Arterial Properties in Relation to Genetic Variations in the Adducin Subunits in a White Population

Background Adducin is a membrane skeleton protein, which consists of either α- and β- or α- and γ-subunits. We investigated whether arterial characteristics might be related to the genes encoding ADD1 (Gly460Trp-rs4961), ADD2 (C1797T-rs4984), and ADD3 (IVS11+386A>G-rs3731566). Methods We randomly recruited 1,126 Flemish subjects (mean age, 43.8 years; 50.3% women). Using a wall-tracking ultrasound system, we measured the properties of the carotid, femoral, and brachial arteries. We studied multivariate-adjusted phenotype-genotype associations, using a population- and family-based approach. Results In single-gene analyses, brachial diameter was 0.15 mm (P = 0.0022) larger, and brachial distensibility and cross-sectional compliance were 1.55 × 10-3/kPa (P = 0.013) and 0.017 mm2/kPa (P = 0.0029) lower in ADD3 AA than ADD3 GG homozygotes with an additive effect of the G allele. In multiple-gene analyses, the association of brachial diameter and distensibility with the ADD3 G allele occurred only in ADD1 GlyGly homozygotes. Otherwise, the associations between the arterial phenotypes in the three vascular beds and the ADD1 or ADD2 polymorphisms were not significant. In family-based analyses, the multivariate-adjusted heritability was 0.52, 0.38, and 0.30 for brachial diameter, distensibility, and cross-sectional compliance, respectively (P < 0.001). There was no evidence for population stratification (0.07 ≤ P ≤ 0.96). Transmission of the mutated ADD3 G allele was associated with smaller brachial diameter in 342 informative offspring (-0.12 ± 0.04 mm; P = 0.0085) and in 209 offspring, who were ADD1 GlyGly homozygotes (-0.14 ± 0.06 mm; P = 0.018). Conclusions In ADD1 GlyGly homozygotes, the properties of the brachial artery are related to the ADD3 (A386G) polymorphism, but the underlying mechanism needs further clarification. American Journal of Hypertension (2009). doi: 10.1038/ajh.2008.26

Cardiovascular end points and mortality are not closer associated with central than peripheral pulsatile blood pressure components

none32Pulsatile blood pressure (BP) confers cardiovascular risk. Whether associations of cardiovascular end points are tighter for central systolic BP (cSBP) than peripheral systolic BP (pSBP) or central pulse pressure (cPP) than peripheral pulse pressure (pPP) is uncertain. Among 5608 participants (54.1% women; mean age, 54.2 years) enrolled in nine studies, median follow-up was 4.1 years. cSBP and cPP, estimated tonometrically from the radial waveform, averaged 123.7 and 42.5 mm Hg, and pSBP and pPP 134.1 and 53.9 mm Hg. The primary composite cardiovascular end point occurred in 255 participants (4.5%). Across fourths of the cPP distribution, rates increased exponentially (4.1, 5.0, 7.3, and 22.0 per 1000 person-years) with comparable estimates for cSBP, pSBP, and pPP. The multivariable-adjusted hazard ratios, expressing the risk per 1-SD increment in BP, were 1.50 (95% CI, 1.33-1.70) for cSBP, 1.36 (95% CI, 1.19-1.54) for cPP, 1.49 (95% CI, 1.33-1.67) for pSBP, and 1.34 (95% CI, 1.19-1.51) for pPP (P<0.001). Further adjustment of cSBP and cPP, respectively, for pSBP and pPP, and vice versa, removed the significance of all hazard ratios. Adding cSBP, cPP, pSBP, pPP to a base model including covariables increased the model fit (P<0.001) with generalized R2 increments ranging from 0.37% to 0.74% but adding a second BP to a model including already one did not. Analyses of the secondary end points, including total mortality (204 deaths), coronary end points (109) and strokes (89), and various sensitivity analyses produced consistent results. In conclusion, associations of the primary and secondary end points with SBP and pulse pressure were not stronger if BP was measured centrally compared with peripherally.noneHuang, Qi-Fang; Aparicio, Lucas S; Thijs, Lutgarde; Wei, Fang-Fei; Melgarejo, Jesus D; Cheng, Yi-Bang; Sheng, Chang-Sheng; Yang, Wen-Yi; Gilis-Malinowska, Natasza; Boggia, José; Niiranen, Teemu J; Wojciechowska, Wiktoria; Stolarz-Skrzypek, Katarzyna; Barochiner, Jessica; Ackermann, Daniel; Tikhonoff, Valérie; Ponte, Belen; Pruijm, Menno; Casiglia, Edoardo; Narkiewicz, Krzysztof; Filipovský, Jan; Czarnecka, Danuta; Kawecka-Jaszcz, Kalina; Jula, Antti M; Bochud, Murielle; Vanassche, Thomas; Verhamme, Peter; Struijker-Boudier, Harry A J; Wang, Ji-Guang; Zhang, Zhen-Yu; Li, Yan; Staessen, Jan AHuang, Qi-Fang; Aparicio, Lucas S; Thijs, Lutgarde; Wei, Fang-Fei; Melgarejo, Jesus D; Cheng, Yi-Bang; Sheng, Chang-Sheng; Yang, Wen-Yi; Gilis-Malinowska, Natasza; Boggia, José; Niiranen, Teemu J; Wojciechowska, Wiktoria; Stolarz-Skrzypek, Katarzyna; Barochiner, Jessica; Ackermann, Daniel; Tikhonoff, Valérie; Ponte, Belen; Pruijm, Menno; Casiglia, Edoardo; Narkiewicz, Krzysztof; Filipovský, Jan; Czarnecka, Danuta; Kawecka-Jaszcz, Kalina; Jula, Antti M; Bochud, Murielle; Vanassche, Thomas; Verhamme, Peter; Struijker-Boudier, Harry A J; Wang, Ji-Guang; Zhang, Zhen-Yu; Li, Yan; Staessen, Jan

Risk Stratification by Cross-Classification of Central and Brachial Systolic Blood Pressure

Background: Whether cardiovascular risk is more tightly associated with central (cSBP) than brachial (bSBP) systolic pressure remains debated, because of their close correlation and uncertain thresholds to differentiate cSBP into normotension versus hypertension.Methods: In a person-level meta-analysis of the International Database of Central Arterial Properties for Risk Stratification (n=5576; 54.1% women; mean age 54.2 years), outcome-driven thresholds for cSBP were determined and whether the cross-classification of cSBP and bSBP improved risk stratification was explored. cSBP was tonometrically estimated from the radial pulse wave using SphygmoCor software.Results: Over 4.1 years (median), 255 composite cardiovascular end points occurred. In multivariable bootstrapped analyses, cSBP thresholds (in mm Hg) of 110.5 (95% CI, 109.1-111.8), 120.2 (119.4-121.0), 130.0 (129.6-130.3), and 149.5 (148.4-150.5) generated 5-year cardiovascular risks equivalent to the American College of Cardiology/American Heart Association bSBP thresholds of 120, 130, 140, and 160. Applying 120/130 mm Hg as cSBP/bSBP thresholds delineated concordant central and brachial normotension (43.1%) and hypertension (48.2%) versus isolated brachial hypertension (5.0%) and isolated central hypertension (3.7%). With concordant normotension as reference, the multivariable hazard ratios for the cardiovascular end point were 1.30 (95% CI, 0.58-2.94) for isolated brachial hypertension, 2.28 (1.21-4.30) for isolated central hypertension, and 2.02 (1.41-2.91) for concordant hypertension. The increased cardiovascular risk associated with isolated central and concordant hypertension was paralleled by cerebrovascular end points with hazard ratios of 3.71 (1.37-10.06) and 2.60 (1.35-5.00), respectively.Conclusions: Irrespective of the brachial blood pressure status, central hypertension increased cardiovascular and cerebrovascular risk indicating the importance of controlling central hypertension.</p

Opposing Age-Related Trends in Absolute and Relative Risk of Adverse Health Outcomes Associated With Out-of-Office Blood Pressure

Participant-level meta-analyses assessed the age-specific relevance of office blood pressure to cardiovascular complications, but this information is lacking for out-of-office blood pressure. At baseline, daytime ambulatory (n=12 624) or home (n=5297) blood pressure were measured in 17 921 participants (51.3% women; mean age, 54.2 years) from 17 population cohorts. Subsequently, mortality and cardiovascular events were recorded. Using multivariable Cox regression, floating absolute risk was computed across 4 age bands (80 years). Over 236 491 person-years, 3855 people died and 2942 cardiovascular events occurred. From levels as low as 110/65 mm Hg, risk log-linearly increased with higher out-of-office systolic/diastolic blood pressure. From the youngest to the oldest age group, rates expressed per 1000 person-years increased (P<0.001) from 4.4 (95% CI, 4.0-4.7) to 86.3 (76.1-96.5) for all-cause mortality and from 4.1 (3.9-4.6) to 59.8 (51.0-68.7) for cardiovascular events, whereas hazard ratios per 20-mm Hg increment in systolic out-of-office blood pressure decreased (P <= 0.0033) from 1.42 (1.19-1.69) to 1.09 (1.05-1.12) and from 1.70 (1.51-1.92) to 1.12 (1.07-1.17), respectively. These age-related trends were similar for out-of-office diastolic pressure and were generally consistent in both sexes and across ethnicities. In conclusion, adverse outcomes were directly associated with out-of-office blood pressure in adults. At young age, the absolute risk associated with out-of-office blood pressure was low, but relative risk high, whereas with advancing age relative risk decreased and absolute risk increased. These observations highlight the need of a lifecourse approach for the management of hypertension