Mechanism of hypertension and coronary atherosclerosis in type 2 diabetes

Mechanism of hypertension and coronary atherosclerosis in type 2 diabetes

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Background: Controversies exist regarding the optimal blood pressure (BP) level that is safe and provides cardiovascular protection in patients with type 2 diabetes mellitus (T2DM) and coexistent coronary artery disease. Several new glucose-lowering agents have been found to lower BP as well, making the interaction between BP and T2DM even more co...

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Background The present survey aimed to find out the demographical and clinical characteristics of patients with hypertension in a population with type 2 diabetes mellitus (T2DM) in Turkey. Methods Patients with T2DM who were followed-up in tertiary endocrine units for at least last one year were recruited. Demographic, clinical and biochemical dat...

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... exercise improves lipid profile (54), and augments myocardial oxygen demand and blood flow, acting as a driving force for arteriogenesis, which helps in coronary collateral formation in patients with stable CAD, exceeding the effect of any drug treatment (55). Similarly, optimal blood pressure control (especially diastolic blood pressure) is crucial in achieving maximal coronary collateral flow (56,57). While dietary quality is important for overall health, the total daily caloric intake per se should be a key determinant of hyperlipidemia in which a hypocaloric plan is favorable for reducing overweight and improving lipid profile and insulin sensitivity (58). ...
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Coronary collateralization is substantially impaired in patients with type 2 diabetes and occlusive coronary artery disease, which leads to aggravated myocardial ischemia and a more dismal prognosis. In a diabetic setting, altered serum lipid profiles and profound glycoxidative modification of lipoprotein particles induce endothelial dysfunction, blunt endothelial progenitor cell response, and severely hamper growth and maturation of collateral vessels. The impact of dyslipidemia and lipid-lowering treatments on coronary collateral formation has become a topic of heightened interest. In this review, we summarized the association of triglyceride-based integrative indexes, hypercholesterolemia, increased Lp(a) with its glycoxidative modification, as well as quantity and quality abnormalities of high-density lipoprotein with impaired collateral formation. We also analyzed the influence of innovative lipid-modifying strategies on coronary collateral development. Therefore, clinical management of diabetic dyslipidemia should take into account of its effect on coronary collateralization in patients with occlusive coronary artery disease.
... cardiovascular disease (CVD) [1,2]. High blood pressure (BP) is one of the major risk factors for development of CVD. ...
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Background High blood pressure is a major risk factor for cardiovascular disease. Visit-to-visit blood pressure variability (BPV) has recently been shown to predict cardiovascular outcomes. We investigated the predictive value of BPV for major adverse cardiovascular events (MACE) among patients with coronary artery disease (CAD), with and without type 2 diabetes mellitus (T2DM). Methods Patients with stable CAD were enrolled and monitored for new MACE. Visit-to-visit BPV was defined as the coefficient of variation (CV) of systolic and diastolic BP across clinic visits. Multivariable logistic regression analysis was performed to evaluate the association of BPV with MACE. Area under the receiver operating characteristic curve (AUC) was used to assess its predictive ability. Results Among 1140 Chinese patients with stable CAD, 192 (17%) experienced a new MACE. In multivariable analyses, the risk of MACE was significantly associated with CV of systolic BP (odds ratio [OR] for highest versus lowest quartile, 3.30; 95% CI 1.97–5.54), and diastolic BP (OR for highest versus lowest quartile, 2.39; 95% CI 1.39–4.11), after adjustment for variables of the risk factor model (age, gender, T2DM, hypertension, antihypertensive agents, number of BP measurements) and mean BP. The risk factor model had an AUC of 0.70 for prediction of MACE. Adding systolic/diastolic CV into the risk factor model with mean BP significantly increased the AUC to 0.73/0.72 (P = 0.002/0.007). In subgroup analyses, higher CV of systolic BP remained significantly associated with an increased risk for MACE in patients with and without T2DM, whereas the association of CV of diastolic BP with MACE was observed only in those without T2DM. Conclusions Visit-to-visit variability of systolic BP and of diastolic BP was an independent predictor of new MACE and provided incremental prognostic value beyond mean BP and conventional risk factors in patients with stable CAD. The association of BPV in CAD patients without T2DM with subsequent risk for MACE was stronger than in those with T2DM.
... In patients with diabetes and high cardiovascular risk who participated in the ONTARGET/TRANSCEND (telmisartan alone and in combination with ramipril) trials, a U-shaped relationship between SBP and adjusted cardiovascular diseases rates in patients with Type 2 diabetes mellitus (T2DM) and established cardiovascular disease or multiple risk factors has been demonstrated. SBP less than 120 mmHg was associated with higher risk for cardiovascular events and death [21,22]. Previous reports demonstrated that telmisartan induced browning of the fully differentiated white adipocytes, at least in part, via PPAR-γ mediated M2 polarization [23]. ...
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Background The prevalence of hypertension and obesity has increased significantly in recent decades. Hypertension and obesity often coexist, and both are associated with increased cardiovascular mortality. Obese hypertensive patients usually require special anti-hypertensive treatment strategy due to the increased risk of treatment resistance. Molecules that can target both obesity and hypertension underlying pathologies should get more attention. Herein, we evaluated the therapeutic effects of telmisartan, with special interest in visceral adipose tissue dysfunction, in obesity-related hypertension rat model. Methods Thirty male Wistar rats weighing 150–200 g were equally divided into: 1—Control group (fed normal laboratory diet for 24 weeks), 2—Diet-induced obesity group (DIO, fed high fat diet for 24 weeks), and 3—Diet-induced obesity treated with telmisartan group (DIO + Tel, fed high fat diet and received telmisartan for 24 weeks). At the end of the study, anthropometrical parameters were evaluated. Systolic blood pressure and heart rate were measured. Blood samples were collected for the measurement of serum lipids, adipokines, cardiac, renal, inflammatory, and oxidative stress biomarkers. Kidneys were removed and used for histopathological studies, and visceral adipose tissue was utilized for histopathological, immunohistochemical and RT-PCR studies. Results High fat diet resulted in obesity-related changes in anthropometrical parameters, elevation of blood pressure, increase in heart rate, higher serum levels of cardiac, inflammatory and kidney function biomarkers, with altered serum lipids, adipokines and oxidative stress markers. Morphological changes (H&E and PAS-stained sections) were noticed in kidneys and visceral adipose tissue. Immunohistochemistry and RT-PCR studies confirmed adipose tissue dysfunction and over-expression of inflammatory and oxidative stress proteins. Telmisartan countered obesity-induced alterations in cardiovascular, renal, and adipose tissue functions. Conclusion Adipose tissue dysfunction could be the core pathophysiology of obesity-related hypertension. Besides its anti-hypertensive effect, telmisartan had profound actions on visceral adipose tissue structure and function. Attention should be given to polymodal molecules targeting adipose tissue-related disorders.
... In a single-arm study, sitagliptin, a dipeptidyl peptidase-4 inhibitor, showed an improvement in FMD measurements in moderately controlled patients with T2DM, in addition to a decrease in HbA1c within 2 weeks of therapy [44]. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a relatively new class of oral anti-diabetic agents with promising cardiovascular benefits, including a slight reduction in blood pressure and arterial stiffness [45][46][47]. The DEFENSE study demonstrated that with dapagliflozin add-on therapy to metformin for 16 weeks, vascular endothelial function as assessed by FMD was significantly ameliorated in patients with inadequately controlled early stage T2DM, and such a beneficial effect was due to improved oxidative stress [48]. ...
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Background We investigated whether glycemic control affects the relation between endothelial dysfunction and coronary artery disease in patients with type 2 diabetes mellitus (T2DM). Methods In 102 type 2 diabetic patients with stable angina, endothelial function was evaluated using brachial artery flow-mediated dilation (FMD) with high-resolution ultrasound, and significant stenosis of major epicardial coronary arteries (≥ 50% diameter narrowing) and degree of coronary atherosclerosis (Gensini score and SYNTAX score) were determined. The status of glycemic control was assessed by blood concentration of glycated hemoglobin (HbA1c). Results The prevalence of significant coronary artery stenosis (67.9% vs. 37.0%, P = 0.002) and degree of coronary atherosclerosis (Gensini score: 48.99 ± 48.88 vs. 15.07 ± 21.03, P < 0.001; SYNTAX score: 15.88 ± 16.36 vs. 7.28 ± 10.54, P = 0.003) were higher and FMD was lower (6.03 ± 2.08% vs. 6.94 ± 2.20%, P = 0.036) in diabetic patients with poor glycemic control (HbA1c ≥ 7.0%; n = 56) compared to those with good glycemic control (HbA1c < 7.0%; n = 46). Multivariate regression analysis revealed that tertile of FMD was an independent determinant of presence of significant coronary artery stenosis (OR = 0.227 95% CI 0.056–0.915, P = 0.037), Gensini score (β = − 0.470, P < 0.001) and SYNTAX score (β = − 0.349, P = 0.004) in diabetic patients with poor glycemic control but not for those with good glycemic control (P > 0.05). Conclusion Poor glycemic control negatively influences the association of endothelial dysfunction and coronary artery disease in T2DM patients.
... However, current study analyzed diabetic patients who were relatively healthy, had no history of CVD and received regular health check-ups. In high-risk diabetics with a history of CVD, the target BP of < 130/80 mmHg may be more appropriate even at the age of ≥ 70 years [29,30]. Otherwise, target BP should not be lowered to < 130/80 mmHg in diabetic patients with comorbidities and high frailty even at the age of < 70 years due to the risk of side effects of intensive BP lowering [31]. ...
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Background Little is known about age-specific target blood pressure (BP) in hypertensive patients with diabetes mellitus (DM). The aim of this study was to determine the BP level at the lowest cardiovascular risk of hypertensive patients with DM according to age. Methods Using the Korean National Health Insurance Service database, we analyzed patients without cardiovascular disease diagnosed with both hypertension and DM from January 2002 to December 2011. Primary end-point was composite cardiovascular events including cardiovascular death, myocardial infarction and stroke. Results Of 241,148 study patients, 35,396 had cardiovascular events during a median follow-up period of 10 years. At the age of < 70 years, the risk of cardiovascular events was lower in patients with BP < 120/70 mmHg than in those with BP 130–139/80–89 mmHg. At the age of ≥ 70, however, there were no significant differences in the risk of cardiovascular events between patients with BP 130–139/80–89 mmHg and BP < 120/70 mmHg. The risk of cardiovascular events was similar between patients with BP 130–139/80–89 mmHg and BP 120–129/70–79 mmHg, and it was significantly higher in those with BP ≥ 140/90 mmHg than in those with BP 130–139/80–89 mmHg at all ages. Conclusions In a cohort of hypertensive patients who had DM but no history of cardiovascular disease, lower BP was associated with lower risk of cardiovascular events especially at the age of < 70. However, low BP < 130–139/80–89 mmHg was not associated with decreased cardiovascular risk, it may be better to keep the BP of 130–139/80–89 mmHg at the age of ≥ 70.
... In this study, T2DM was the only independent risk factor for poor coronary collateralization, suggesting that presence of T2DM is correlated negatively with the development of functional collateral arteries [24,25], and may contribute partially to adverse prognosis of CTO patients [38]. Although presence of a chronic totally occluded lesion has been considered as a prerequisite for spontaneous collateral recruitment, the mechanism of collateral vessel growth is complex in situations where atherosclerosis affects large conductance arteries [39], and even becomes more complicated by the presence of T2DM in which multiple biochemical and cellular components are involved [25,40,41]. ...
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Background: To assess the prognostic role of coronary collaterals in patients with type 2 diabetes mellitus (T2DM) after successful percutaneous coronary intervention (PCI) for chronic total occlusion (CTO). Methods: Coronary collateralization was graded according to Rentrop scoring system in 198 type 2 diabetic patients and 335 non-diabetics with stable angina undergoing PCI for at least one CTO lesion. Left ventricular ejection fraction (LVEF) was determined and major adverse cardio-cerebral events (MACCE) were recorded during follow-up. Results: Poor collateralization was more common in patients with T2DM than in non-diabetics (40% vs 29%, p = 0.008). At 13.5 ± 4.1 months, the rate of composite MACCE (17.3% vs 27.6%, p = 0.034) and repeat revascularization (15.2% vs 25.5%, p = 0.026) was lower and the increase in LVEF (3.10% vs 1.80%, p = 0.024) was greater in patients with good collaterals than in those with poor collaterals for non-diabetic group. The associations were in the same direction for T2DM group (35% vs 44%; 30% vs 36%; 2.14% vs 1.65%, respectively) with a higher all-cause mortality in diabetic patients with poor collaterals (p = 0.034). Multivariable Cox proportional hazards analysis showed that coronary collateralization was an independent factor for time to MACCE (HR 2.155,95% CI 1.290-3.599, p = 0.003) and repeat revascularization (HR 2.326, 95% CI 1.357-3.986, p = 0.002) in non-diabetic patients, but did not enter the model in those with T2DM. Conclusions: T2DM is associated with reduced coronary collateralization. The effects of the status of coronary collateralization on long-term clinical outcomes and left ventricular function appear to be similar in size in type 2 diabetic patients and non-diabetics after successful recanalization of CTO.
... In this study, T2DM was the only independent risk factor for poor coronary collateralization, suggesting that presence of T2DM is correlated negatively with the development of functional collateral arteries 22,23 , and may contribute partially to adverse prognosis of CTO patients 36 . Although presence of a chronic totally occluded lesion has been considered as a prerequisite for spontaneous collateral recruitment, the mechanism of collateral vessel growth is complex in situations where atherosclerosis affects large conductance arteries 37 , and even become more complicated by the presence of T2DM in which multiple biochemical and cellular components are involved 23, 38,39 . ...
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Background: To assess the prognostic role of coronary collaterals in patients with type 2 diabetes mellitus (T2DM) after successful percutaneous coronary intervention (PCI) for chronic total occlusion (CTO). Methods: Coronary collateralization was graded according to Rentrop scoring system in 198 type 2 diabetic patients and 335 non-diabetics with stable angina undergoing PCI for at least one CTO lesion. Left ventricular ejection fraction (LVEF) was determined and major adverse cardio-cerebral events (MACCE) were recorded during follow-up. Results: Poor collateralization was more common in patients with T2DM than in non-diabetics (40% vs 29%, p=0.008). At 13.5±4.1 months, the rate of composite MACCE (17.3% vs 27.6%, p=0.034) and repeat revascularization (15.2% vs 25.5%, p=0.026) was lower and the increase in LVEF (3.10 % vs 1.80%, p=0.024) was greater in patients with good collaterals than in those with poor collaterals for non-diabetic group, but did not differ for T2DM group (35% vs 44%; 30% vs 36%; 2.14% vs 1.65%, respectively, all p>0.05) except for a higher all-cause mortality in diabetic patients with poor collaterals (p=0.034). Multivariable Cox proportional hazards analysis showed that coronary collateralization was an independent factor for time to MACCE (HR 2.155,95%CI 1.290-3.599, P=0.003) and repeat revascularization (HR 2.326, 95%CI 1.357-3.986, p=0.002) in non-diabetic patients, but did not enter the model in those with T2DM. Conclusions: T2DM is associated with reduced coronary collateralization. Successful revascularization of CTO lesions results in a mild improvement in left ventricular function, but t he status of coronary collaterals has no independent effect on long-term clinical outcomes in patients with T2DM.
... In this study, T2DM was the only independent risk factor for poor coronary collateralization, suggesting that presence of T2DM is correlated negatively with the development of functional collateral arteries 24,25 , and may contribute partially to adverse prognosis of CTO patients 38 . Although presence of a chronic totally occluded lesion has been considered as a prerequisite for spontaneous collateral recruitment, the mechanism of collateral vessel growth is complex in situations where atherosclerosis affects large conductance arteries 39 , and even becomes more complicated by the presence of T2DM in which multiple biochemical and cellular components are involved 25,40,41 . ...
Preprint
Full-text available
Background: To assess the prognostic role of coronary collaterals in patients with type 2 diabetes mellitus (T2DM) after successful percutaneous coronary intervention (PCI) for chronic total occlusion (CTO). Methods: Coronary collateralization was graded according to Rentrop scoring system in 198 type 2 diabetic patients and 335 non-diabetics with stable angina undergoing PCI for at least one CTO lesion. Left ventricular ejection fraction (LVEF) was determined and major adverse cardio-cerebral events (MACCE) were recorded during follow-up. Results: Poor collateralization was more common in patients with T2DM than in non-diabetics (40% vs 29%, p=0.008). At 13.5±4.1 months, the rate of composite MACCE (17.3% vs 27.6%, p=0.034) and repeat revascularization (15.2% vs 25.5%, p=0.026) was lower and the increase in LVEF (3.10 % vs 1.80%, p=0.024) was greater in patients with good collaterals than in those with poor collaterals for non-diabetic group. The associations were in the same direction for T2DM group (35% vs 44%; 30% vs 36%; 2.14% vs 1.65%, respectively) with a higher all-cause mortality in diabetic patients with poor collaterals (p=0.034). Multivariable Cox proportional hazards analysis showed that coronary collateralization was an independent factor for time to MACCE (HR 2.155,95%CI 1.290-3.599, P=0.003) and repeat revascularization (HR 2.326, 95%CI 1.357-3.986, p=0.002) in non-diabetic patients, but did not enter the model in those with T2DM. Conclusions: T2DM is associated with reduced coronary collateralization. The effects of the status of coronary collateralization on long-term clinical outcomes and left ventricular function appear to be similar in size in type 2 diabetic patients and non-diabetics after successful recanalization of CTO.
... This reduces collateral flow. This fall is approximately 20% if DBP is 70-79 mm of Hg, 28% if DBP is 60-69 mm of Hg, and 38% if DBP is <60 mm of Hg. [4] ...
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E-selectin is an endothelial cell adhesion molecule involved in vascular inflammation. Elevated E-selectin has been reported in patients with high blood pressure and diabetes. Given the increasing clinical relevance of parameters derived from ambulatory blood pressure monitoring, further investigation of their relationships with E-selectin is of interest. In this study, we aimed to investigate the association between serum E-selectin, office blood pressure and 24 h ambulatory blood pressure parameters in patients with type 2 diabetes. Blood pressure variability was assessed by computing the standard deviation of mean systolic and diastolic blood pressure separately for daytime and nighttime during 24 h ambulatory blood pressure monitoring in a cohort of patients with type 2 diabetes (n = 132). Additionally, were assessed nighttime systolic dipping and pulse pressure separately for daytime, nighttime, and 24 h. Serum E-selectin was measured using the enzyme-linked immunosorbent assay technique. We found that E-selectin was consistently associated with 24 h diastolic blood pressure variability (r = 0.238; p = 0.019) and daytime diastolic blood pressure variability (r = 0.258; p = 0.012), after adjustment for confounding factors. No association of E-selectin with office blood pressure and other 24 h ambulatory blood pressure parameters was observed. In conclusion, endothelial activation indicated by elevated serum E-selectin is associated with increased ambulatory diastolic blood pressure variability in patients with type 2 diabetes.