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Objectives: The prevalence of dementia is growing rapidly worldwide. The early identification and treatment of cognitive decline could reduce the burden on the health care system. Our objective was to investigate whether factors measured at an examination at age 50 predict cognitive impairment (CI) 23 years later., Materials & Methods: In 1993 we enrolled a randomly selected sample of 798 men, 50 years of age, from the general population. They all underwent a physical examination, provided blood samples and filled out questionnaires addressing lifestyle and psychosocial factors. Cognitive testing was offered to all participants still alive in 2016, at age 73., Results: A total of 333 men participated in the cognitive study, of which 80 (24.0%) performed at a level corresponding to mild cognitive impairment, and four (1.2%) at a level consistent with severe cognitive impairment. After the first step in the multivariable analysis, hypertension, heavy smoking, high intake of alcohol, financial stress, difficulty falling asleep, and cogwheel rigidity were associated with cognitive impairment. After further adjustment, only wide waist circumference measured in cm (OR 1.04, 95% CI 1.00-1.08, p = .04), leg pendulousness (OR 41.97, 95% CI 3.27-538.62, p = .004) and self-assessed hidden irritability (OR 2.18, 95% CI 1.10-4.32, p = .03) at baseline, remained as being associated with cognitive impairment 23 years later., Conclusions: Extrapyramidal symptoms such as leg pendulousness, at the age of 50, may be an indicator for very early identification of future cognitive decline., (© 2021 The Authors. Acta Neurologica Scandinavica published by John Wiley & Sons Ltd.)

Background: The link between type 2 diabetes and hypertension is well established and the conditions often coexist. High normal blood pressure, defined by WHO-ISH as systolic blood pressure (SBP) 130-139 mm Hg or diastolic blood pressure (DBP) 85-89 mm Hg, has been found to be an independent predictor for type 2 diabetes in studies, although with relatively limited follow-up periods of approximately 10 years. The aim of this study was to investigate whether hypertension, including mildly elevated blood pressure within the normal range, predicted subsequent development of type 2 diabetes in men over an extended follow-up of 35 years., Methods: Data were derived from the Gothenburg Primary Prevention Study where a random sample of 7 494 men aged 47-55 years underwent a baseline screening investigation in the period 1970-1973. A total of 7 333 men were free from previous history of diabetes at baseline. During a 35-year follow-up diabetes was identified through the Swedish hospital discharge and death registries. The cumulative risk of diabetes adjusted for age and competing risk of death was calculated. Using Cox proportional hazard models we calculated the multiple adjusted hazard ratios (HR) (95% confidence interval (CI)) for diabetes at different blood pressure levels., Results: During a 35-year follow-up, 956 men (13%) were identified with diabetes. The 35-year cumulative risk of diabetes after adjusting for age and competing risk of death in men with SBP levels <130 mm Hg, 130-139 mm Hg, 140-159 mm Hg and ≥160 mm Hg were 19%, 30%, 31% and 49%, respectively. The HR for diabetes adjusted for age, body mass index (BMI), cholesterol, antihypertensive treatment, smoking, physical activity and occupation were 1.43 (95% CI 1.12-1.84), 1.43 (95% CI 1.14-1.79) and 1.95 (95% CI 1.55-2.46) for men with SBP 130-139 mm Hg, 140-159 mm Hg, and ≥ 160 mm Hg, respectively (reference; SBP<130 mm Hg)., Conclusion: In this population, at mid-life, even high-normal SBP levels were shown to be a significant predictor of type 2 diabetes, independently of BMI and other conventional type 2 diabetes risk factors over an extended follow-up.

Objective: We have previously shown an enhanced expression of Gialpha proteins in spontaneously hypertensive rats (SHR) that precedes the development of hypertension. Since oxidative stress has been shown to be increased in SHR, the present studies were undertaken to examine the role of oxidative stress in enhanced expression of Gialpha proteins in SHR., Methods: Aortic vascular smooth muscle cells (VSMC) from 12-week-old SHR and Wistar-Kyoto (WKY) rats were used for the present studies. The levels of inhibitory guanine nucleotide regulatory proteins (Gialpha-2 and Gialpha-3) and stimulatory proteins (Gsalpha) were determined by western blotting techniques. Adenylyl cyclase activity was determined by measuring [32P]cAMP formation from [alpha-32P]ATP., Results: VSMC from SHR exhibited enhanced expression of Gialpha-2 and Gialpha-3 proteins as compared with age-matched WKY rats; however, the levels of Gsalpha proteins were not different between the two groups. The levels of superoxide anion (O2-) were also increased in SHR as compared with WKY rats, and losartan, an AT1 receptor antagonist, restored the enhanced levels to control WKY rat levels. Treatment of VSMC with antioxidants such as N-acetyl-L-cysteine (NAC) or diphenyleneiodonium (DPI) for 24 h decreased the enhanced expression of Gialpha-2 and Gialpha-3 proteins in a concentration-dependent manner in VSMC from SHR. In addition, the inhibition of forskolin-stimulated enzyme activity by low concentrations of GTPgammaS (receptor-independent Gi functions) and C-ANP4-23-mediated inhibition of adenylyl cyclase (receptor-dependent Gi functions) that were significantly enhanced in SHR were restored to WKY rat levels by NAC and DPI treatments. Similarly, diminished stimulation of adenylyl cyclase by GTPgammaS, isoproterenol and sodium fluoride in SHR was also restored towards control WKY rat levels by NAC and DPI treatments. Furthermore, PD98059, a selective inhibitor of mitogen-activated protein kinase, was able to restore the enhanced expression of Gialpha proteins in VSMC from SHR towards WKY rat levels. In addition, the enhanced activity of extracellular signal-regulated kinase 1/2 in SHR as compared with WKY rats, as demonstrated by enhanced phosphorylation of extracellular signal-regulated kinase 1/2, was also restored to WKY rat levels by NAC or DPI., Conclusions: These results suggest that enhanced levels of Gialpha proteins and associated functions in SHR may be attributed to the enhanced oxidative stress present in SHR, which exerts its effects through the mitogen-activated protein kinase signaling pathway.

Background: Favourable trends in cardiovascular disease have been observed in Sweden. The aim of this study was to study secular trends in a variety of cardiovascular risk factors., Methods: Total-, low-density (LDL) and high-density lipoprotein (HDL) serum cholesterol; serum triglycerides; systolic and diastolic blood pressure; self-reported smoking and alcohol consumption were studied in repeated cross-sectional surveys. Data from four population-based samples in Goteborg, Sweden were used-WHO MONICA project 1985, 1990 and 1995, and INTERGENE 2002. A total of 2931 females and 2691 males aged 25-64 consisting of 1021-1624 randomly selected subjects at each survey period participated., Results: Serum cholesterol levels showed downward trends but the decline in both total- and LDL-cholesterol seems to be levelling off from 1995 and onwards. No significant changes were observed in serum triglyceride, HDL-serum cholesterol or blood pressure levels. The majority of the participants had higher total- and LDL-serum cholesterol levels than currently recommended. Antihypertensive medical treatment increased in women and the oldest men. The prevalence of smoking decreased from 39 to 25% in women and 35 to 20% in men respectively from 1985-2002. In contrast, the prevalence of subjects consuming strong beer and wine, respectively, at least once a week almost doubled from 1990-2002., Conclusions: Cardiovascular risk factor patterns change continuously and need to be monitored. The favourable trends in LDL-serum cholesterol and smoking in the Goteborg surveys were paralleled by less favourable trends in being overweight and alcohol consumption.

Abstract: We have recently shown that vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats (SHR) exhibit enhanced expression of Giα proteins, which was attributed to the enhanced oxidative stress. Since C-ANP4–23 that specifically interacts with natriuretic peptide C (NPR-C) receptor has been shown to decrease the expression of Giα protein in VSMC, the present study was undertaken to examine if C-ANP4–23 can also decrease the enhanced expression of Giα protein in VSMC from SHR and whether it is attributed to its ability to attenuate the enhanced oxidative stress. Aortic VSMC from 12-week-old SHR and their age-matched Wistar–Kyoto (WKY) rats were used for the present studies. VSMC from SHR exhibited enhanced expression of Giα-2 and Giα-3 proteins, different subunits of NADPH oxidase such as Nox4 and p47phox proteins but not of p22phox, enhanced production of superoxide anion as well as NADPH oxidase activity as compared to age-matched WKY rats. Treatment of VSMC from SHR with C-ANP4–23 decreased towards control levels the enhanced expression of Giα proteins, enhanced superoxide anion production and enhanced NADPH oxidase activity as well as the enhanced expression of Nox4 and p47phox. However, C-ANP4–23-induced attenuation of the enhanced level of O2 − and NADPH oxidase activity occurs at 4 h before the decrease in the enhanced expression of p47phox that occurs at 16 h of C-ANP4–23 treatment. The decreased expression of NADPH oxidase in SHR was also associated with further decrease in O2 − and NADPH oxidase activity. Furthermore, treatment of VSMC from SHR with pertussis toxin (PT) decreased the enhanced levels of superoxide anion as well as NADPH oxidase activity; however, the enhanced levels of different subunits of NADPH oxidase were not attenuated by PT treatment. These results suggest that C-ANP4–23 decreases the enhanced oxidative stress in SHR by attenuating the enhanced expression of Giα proteins and also the enhanced levels of NADPH oxidase. [Copyright &y& Elsevier]